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0000-0002-1278-6245
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Icahn School of Medicine at Mount Sinai
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Publisher: Springer Science and Business Media LLC
Date: 02-03-2010
DOI: 10.1038/IJO.2010.42
Abstract: The purpose of this study was to ascertain the impact of obesity on the cost of disease management in people with or at high risk of atherothrombotic disease from a governmental perspective using a bottom-up approach to cost estimation. In addition, the aim was also to explore the causes of any differences found. The health-care costs of obesity were estimated from 2819 participants recruited into the nationwide Australian REACH Registry with established atherothrombotic disease or at least three risk factors for atherothrombosis. Enrollment was in 2004, through primary care general practices. Information was collected on the use of cardiovascular drugs, hospitalizations and ambulatory care services. 'Bottom-up' costing was undertaken by assigning unit costs to each health-care item, based on Australian Government-reimbursed figures 2006-2007. Linear-mixed models were used to estimate associations between direct medical costs and body mass index (BMI) categories. Annual pharmaceutical costs per person increased with increasing BMI category, even after adjusting for gender, age, living place, formal education, smoking status, hypertension and diabetes. Adjusted annual pharmaceutical costs of overweight and obese participants were higher ($7 (P=0.004) and $144 (<0.001), respectively) than those of the normal weight participants. This was due to participants in higher BMI categories receiving more pharmaceuticals than normal weight participants. There was no significant change across the BMI categories in annual ambulatory care costs and annual hospital costs. In these participants with or at high risk of atherothrombotic disease, annual pharmaceutical costs were greater in participants of higher BMI category, but there was not such a gradient in the annual hospital or ambulatory care costs. The greater cardiovascular pharmaceutical costs for participants of higher BMI categories remained even after adjusting for a range of demographic factors and comorbidities. Our results suggest that these costs are explained by the higher number of drugs used among people with atherothrombotic disease. Further investigation is needed to understand the reasons for this level of drug use.
Publisher: American Medical Association (AMA)
Date: 23-10-2013
Abstract: Among nontraditional cardiovascular risk factors, recent influenzalike infection is associated with fatal and nonfatal atherothrombotic events. To determine if influenza vaccination is associated with prevention of cardiovascular events. A systematic review and meta-analysis of MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013) for randomized clinical trials (RCTs) comparing influenza vaccine vs placebo or control in patients at high risk of cardiovascular disease, reporting cardiovascular outcomes either as efficacy or safety events. Two investigators extracted data independently on trial design, baseline characteristics, outcomes, and safety events from published manuscripts and unpublished supplemental data. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up. Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for composite cardiovascular events, cardiovascular mortality, all-cause mortality, and in idual cardiovascular events. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization. Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years 51.3% women 36.2% with a cardiac history mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7% RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data. In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess in idual cardiovascular end points.
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000118380
Abstract: i Background: /i Aspirin offers modest reduction in stroke in patients with atrial fibrillation. Whether combination of aspirin with clopidogrel offers additional protection is unclear. i Methods: /i Post-hoc subgroup analysis of 593 participants with a history of atrial fibrillation in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) randomized trial testing clopidogrel 75 mg per day plus aspirin (75–162 mg per day) vs. aspirin alone in patients with stable cardiovascular disease or multiple cardiovascular risk factors. i Results: /i Mean patient age was 70 years, 78% were men, and hypertension, heart failure and diabetes were present in 78, 20 and 44%, respectively. During a median follow-up of 2.3 years, stroke (ischemic and hemorrhagic) occurred in 15 of 298 assigned to clopidogrel plus aspirin and in 14 of 285 given aspirin alone (hazard ratio, HR, 1.03, 95% CI 0.49–2.1). There was no difference in all-cause mortality (HR 1.1, 95% CI 0.6–1.9) or in the composite of stroke, myocardial infarction, or vascular death (HR = 1.2, 95% CI 0.7–2.0). Severe/fatal extracranial hemorrhage occurred in 6 patients with combination vs. 3 with aspirin alone. i Conclusions: /i This post-hoc subgroup analysis does not support the use of this combination over aspirin alone in patients with a history of atrial fibrillation pending results of ongoing larger randomized trials.
Publisher: Wiley
Date: 27-11-2013
Abstract: The aim of the study is to determine the extent of lost therapeutic benefit (LTB) in the hypertensive patients, and to determine the relationship between the presence of LTB and clinical outcomes. Prospective-cohort study of n = 2856 patients with or at high risk of atherothrombosis. LTB was calculated as the proportion of patients receiving blood pressure medication who were not attaining guideline blood pressure (BP) control targets ( 65 years (OR = 1.36 [1.06-1.75]) and having an ABI 65 and ABI < 0.09 increased the risk of LTB. Patients with LTB in age category 55-64 had higher incidence of vascular events compared with those with non-LTB.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JACC.2019.07.015
Abstract: Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. The primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896) index CABG after qualifying ACS, but before randomization (n = 1,025) or CABG before the qualifying ACS (n = 1,003). In each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab NCT01663402).
Publisher: American College of Physicians
Date: 17-03-2009
DOI: 10.7326/0003-4819-150-6-200903170-00006
Abstract: The optimal aspirin dose for the prevention of cardiovascular events remains controversial. To assess the incidence of and risk factors for adverse clinical outcomes by investigator-determined aspirin dose in a primary prevention trial. Post hoc observational analyses of data from a double-blind, placebo-controlled, randomized trial. Outpatient. 15 595 patients with cardiovascular disease or multiple risk factors. Clopidogrel, 75 mg/d, or placebo, with aspirin, 75 to 162 mg/d, as selected by the investigators. Incidence of the composite outcome of myocardial infarction, stroke, or cardiovascular death (efficacy end point), and incidence of severe or life-threatening bleeding (safety end point), at a median of 28 months (interquartile range, 23 to 31 months) of follow-up. Daily aspirin doses were categorized as less than 100 mg (75 or 81 mg) (n = 7180), 100 mg (n = 4961), and greater than 100 mg (150 or 162 mg) (n = 3454). The hazard of the primary efficacy end point was the same regardless of dose (adjusted hazard ratio, 0.95 [95% CI, 0.80 to 1.13] for 100 mg vs. less than 100 mg, and 1.0 [CI, 0.85 to 1.18] for greater than 100 mg vs. less than 100 mg). The hazard of the primary safety end point also did not depend on dose (adjusted hazard ratio, 0.85 [CI, 0.57 to 1.26] for 100 mg vs. less than 100 mg and 1.05 [CI, 0.74 to 1.48] for greater than 100 mg vs. less than 100 mg). In patients also receiving clopidogrel, daily aspirin doses greater than 100 mg seemed to be non-statistically significantly associated with reduced efficacy (adjusted hazard ratio, 1.16 [CI, 0.93 to 1.44]) and increased harm (adjusted hazard ratio, 1.30 [CI, 0.83 to 2.04]). The analysis was post hoc, and aspirin use was not randomized or blinded. Daily aspirin doses of 100 mg or greater were associated with no clear benefit in patients taking aspirin only and possibly with harm in patients taking clopidogrel. Daily doses of 75 to 81 mg may optimize efficacy and safety for patients requiring aspirin for long-term prevention, especially for those receiving dual antiplatelet therapy. None.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Oxford University Press (OUP)
Date: 30-06-2021
Abstract: To analyse whether the benefits and risks of rivaroxaban plus aspirin vary in patients with comorbidities and receiving multiple drugs. In patients with coronary or peripheral artery disease, adding low-dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients. We describe ischaemic events (cardiovascular death, stroke, or myocardial infarction) and major bleeding in participants from the randomized, double-blind COMPASS study by number of cardiovascular medications and concomitant medical conditions. We compared event rates and hazard ratios (HRs) for rivaroxaban plus aspirin vs. aspirin alone by the number of medications and concomitant conditions, and tested for interaction between polypharmacy or multimorbidity and the antithrombotic regimen. The risk of ischaemic events was higher in patients with more concomitant drugs (HR 1.7, 95% confidence interval 1.5–2.1 for & vs. 0–2) and with more comorbidities (HR 2.3, 1.8–2.1 for & vs. 0–1). Multimorbidity, but not polypharmacy, was associated with a higher risk of major bleeding. The relative efficacy, safety, and net clinical benefit of rivaroxaban were not affected by the number of drugs or comorbidities. Patients taking more concomitant medications derived the largest absolute reduction in the net clinical outcome with added rivaroxaban (1.1% vs. 0.4% reduction with & vs. 0–2 cardiovascular drugs, number needed to treat 91 vs. 250). Adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients.
Publisher: BMJ
Date: 09-2017
DOI: 10.1136/BMJOPEN-2016-014608
Abstract: The European Centre for Disease Prevention and Control is developing evidence-based guidance for voluntary screening, treatment and vaccine prevention of infectious diseases for newly arriving migrants to the European Union/European Economic Area. The objective of this systematic review protocol is to guide the identification, appraisal and synthesis of the best available evidence on prevention and assessment of the following priority infectious diseases: tuberculosis, HIV, hepatitis B, hepatitis C, measles, mumps, rubella, diphtheria, tetanus, pertussis, poliomyelitis (polio), Haemophilus influenza disease, strongyloidiasis and schistosomiasis. The search strategy will identify evidence from existing systematic reviews and then update the effectiveness and cost-effectiveness evidence using prospective trials, economic evaluations and/or recently published systematic reviews. Interdisciplinary teams have designed logic models to help define study inclusion and exclusion criteria, guiding the search strategy and identifying relevant outcomes. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. There are no ethical or safety issues. We anticipate disseminating the findings through open-access publications, conference abstracts and presentations. We plan to publish technical syntheses as GRADEpro evidence summaries and the systematic reviews as part of a special edition open-access publication on refugee health. We are following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols reporting guideline. This protocol is registered in PROSPERO: CRD42016045798.
Publisher: Elsevier BV
Date: 2018
Publisher: Massachusetts Medical Society
Date: 14-01-2021
Publisher: Massachusetts Medical Society
Date: 19-10-2017
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.JACC.2006.10.054
Abstract: We examined the safety and efficacy of nonculprit multivessel compared with culprit-only stenting in patients with multivessel disease presenting with unstable angina or non-ST-segment elevation myocardial infarction (non-ST-segment elevation acute coronary syndromes [NSTE-ACS]). In patients presenting with NSTE-ACS, multivessel coronary artery disease (CAD) is associated with adverse outcome. Patients with multivessel CAD and NSTE-ACS that underwent percutaneous coronary intervention were included. The culprit lesion was defined by reviewing each patient's angiographic report, electrocardiogram, echocardiogram and, if available, nuclear stress test. All patients had at least 2 vessels with > or =50% stenosis, and the angiographic severity of CAD was assessed using the Duke Prognostic Angiographic Score. Patients with coronary bypass grafts, chronic total occlusions, and those with uncertain culprit lesions were excluded. Our end point was the composite of death, myocardial infarction, or any target vessel revascularization. From January 1995 to June 2005, 1,240 patients with ACS and multivessel CAD underwent percutaneous coronary intervention with bare-metal stenting and met our study criteria. Of these, 479 underwent multivessel and 761 underwent culprit-only stenting. There were 442 events during a median follow-up of 2.3 years. Multivessel intervention was associated with lower death, myocardial infarction, or revascularization after both adjusting for baseline and angiographic characteristics (hazard ratio 0.80 95% confidence interval 0.64 to 0.99 p = 0.04) and propensity matched analysis (hazard ratio 0.67 95% confidence interval 0.51 to 0.88 p = 0.004). In patients with multivessel CAD presenting with NSTE-ACS, multivessel intervention was significantly associated with a lower revascularization rate, which translated to a lower incidence of the composite end point compared with culprit-only stenting.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-10-2023
DOI: 10.1161/CIRCULATIONAHA.123.064090
Abstract: Graft patency is the postulated mechanism for the benefits of coronary artery bypass grafting (CABG). However, systematic graft imaging assessment after CABG is rare, and there is a lack of contemporary data on the factors associated with graft failure and on the association between graft failure and clinical events after CABG. We pooled in idual patient data from randomized clinical trials with systematic CABG graft imaging to assess the incidence of graft failure and its association with clinical risk factors. The primary outcome was the composite of myocardial infarction or repeat revascularization occurring after CABG and before imaging. A 2-stage meta-analytic approach was used to evaluate the association between graft failure and the primary outcome. We also assessed the association between graft failure and myocardial infarction, repeat revascularization, or all-cause death occurring after imaging. Seven trials were included comprising 4413 patients (mean age, 64.4±9.1 years 777 [17.6%] women 3636 [82.4%] men) and 13 163 grafts (8740 saphenous vein grafts and 4423 arterial grafts). The median time to imaging was 1.02 years (Q1 Q3: 1.00 .03). Graft failure occurred in 1487 (33.7%) patients and in 2190 (16.6%) grafts. Age (adjusted odds ratio [aOR], 1.08 [per 10-year increment] [95% CI, 1.01–1.15] P =0.03), female sex (aOR, 1.27 [95% CI, 1.08–1.50] P =0.004), and smoking (aOR, 1.20 [95% CI, 1.04–1.38] P =0.01) were independently associated with graft failure, whereas statins were associated with a protective effect (aOR, 0.74 [95% CI, 0.63–0.88] P .001). Graft failure was associated with an increased risk of myocardial infarction or repeat revascularization occurring between CABG and imaging assessment (8.0% in patients with graft failure versus 1.7% in patients without graft failure aOR, 3.98 [95% CI, 3.54–4.47] P .001). Graft failure was also associated with an increased risk of myocardial infarction or repeat revascularization occurring after imaging (7.8% versus 2.0% aOR, 2.59 [95% CI, 1.86–3.62] P .001). All-cause death after imaging occurred more frequently in patients with graft failure compared with patients without graft failure (11.0% versus 2.1% aOR, 2.79 [95% CI, 2.01–3.89] P .001). In contemporary practice, graft failure remains common among patients undergoing CABG and is strongly associated with adverse cardiac events.
Publisher: Oxford University Press (OUP)
Date: 19-11-2020
DOI: 10.1093/EURHEARTJ/EHAA956
Abstract: The aim of this study was to evaluate the temporal pattern of utations in patients with type 2 diabetes mellitus (T2DM), the risk of utations by new and older anti-diabetic drugs (ADDs), and the interplay of peripheral artery disease (PAD) with therapy and utation risk. Using Centricity Electronic Medical Records from USA, 3 293 983 patients with T2DM were identified: 169 739 received sodium-glucose cotransporter type-2 inhibitors (SGLT-2i no exposure to incretins) 149 826 received glucagon-like peptide 1 receptor agonists [GLP-1RA, no SGLT-2i or dipeptidyl peptidase-4 inhibitor (DPP-4i) exposure] 448 225 received DPP-4i (no exposure to GLP-1RA or SGLT-2i) and 1 954 353 received other ADDs. The proportion of incident utations per 10 000 adults ranged between 4.7 and 6.8 during 2000–08 and significantly increased to 12.3 in 2017. Over 17 211 719 person-years follow-up post T2DM diagnosis, the rates per 1000 person-years of any and lower limb utations (LLAs) were similar between SGLT-2i and incretins [95% confidence interval (CI) range: 1.06–1.67], and significantly higher in other groups (95% CI range: 1.96–2.29). In propensity score-adjusted pairwise analyses, the risk of LLA was not higher in SGLT-2i vs. GLP1-RA [hazard ratio (HR) (95% CI): 0.88 (0.73, 1.05)], and lower in SGLT-2i vs. DPP-4i/other ADD [HR (95% CI): 0.65 (0.56, 0.75)/0.43 (0.37, 0.49)]. The rate of LLA was similar in patients treated with canagliflozin, empagliflozin, or dapagliflozin. Patients with PAD had more than four-fold higher LLA risk (range of 95% CI of HR: 3.6–6.0). The risk of utation in patients treated with SGLT-2i and incretins was not higher compared with other ADDs. Pre-existing PAD was the greatest driver of utation risk.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JACC.2019.02.079
Abstract: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the combination of low-dose rivaroxaban and aspirin reduced major vascular events in patients with stable vascular disease. The purpose of this study was to identify subsets of patients at higher risk of recurrent vascular events, which may help focus the use of rivaroxaban and aspirin therapy. COMPASS patients with vascular disease were risk stratified using 2 methods: the REACH (REduction of Atherothrombosis for Continued Health) atherothrombosis risk score and CART (Classification and Regression Tree) analysis. The absolute risk differences for rivaroxaban with aspirin were compared to aspirin alone over 30 months for the composite of cardiovascular death, myocardial infarction, stroke, acute limb ischemia, or vascular utation for severe bleeding and for the net clinical benefit. High-risk patients using the REACH score were those with 2 or more vascular beds affected, history of heart failure (HF), or renal insufficiency, and by CART analysis were those with ≥2 vascular beds affected, history of HF, or diabetes. Rivaroxaban and aspirin combination reduced the serious vascular event incidence by 25% (4.48% vs. 5.95%, hazard ratio: 0.75 95% confidence interval: 0.66 to 0.85), equivalent to 23 events prevented per 1,000 patients treated for 30 months, at the cost of a nonsignificant 34% increase in severe bleeding (1.34 95% confidence interval: 0.95 to 1.88), or 2 events caused per 1,000 patients treated. Among patients with ≥1 high-risk feature identified from the CART analysis, rivaroxaban and aspirin prevented 33 serious vascular events, whereas in lower-risk patients, rivaroxaban and aspirin treatment led to the avoidance of 10 events per 1,000 patients treated for 30 months. In patients with vascular disease, further risk stratification can identify higher-risk patients (≥2 vascular beds affected, HF, renal insufficiency, or diabetes). The net clinical benefit remains favorable for most patients treated with rivaroxaban and aspirin compared with aspirin.
Publisher: Wiley
Date: 18-07-2016
DOI: 10.1002/CCD.26653
Abstract: Whether the efficacy and safety of dual antiplatelet therapy (DAPT) are uniform between sexes is unclear. We sought to compare clinical outcomes between short- (≤6 months) versus long-term (≥1 year) DAPT after drug-eluting stent (DES) placement in women and men. We pooled in idual patient data from 6 randomized trials of DAPT (EXCELLENT, OPTIMIZE, PRODIGY, RESET, SECURITY, ITALIC PLUS). The primary outcome was 1-year risk of major adverse cardiac events (MACE). The main secondary outcome was 1-year risk of any bleeding. Out of the 11,473 randomized patients included in the pooled dataset, 3,454 (30%) were females. At 1-year follow-up, women had higher risk of MACE (3.6% vs. 2.8% P = 0.01) but similar risk of bleeding (1.9% vs. 1.6% P = 0.16) as compared with men. Compared with long-term DAPT, short-term DAPT was associated with similar rates of MACE in both women (HR 0.88 95% CI 0.62-1.25) and men (HR 1.25 95% CI 0.95-1.6 P interaction = 0.08)]. At 1-year follow-up, short-term DAPT was associated with lower rates of bleeding as compared with long-term DAPT in both women (HR 0.84 95% CI 0.51-1.37) and men (HR 0.58 95% CI 0.40-0.84 P-interaction = 0.25). The presence of MVD was associated with higher MACE rates in the short-term DAPT group in women (HR: 1.16 CI 0.60-2.23) and men (HR: 2.29 CI 1.22-4.29 P interaction = 0.25). Short-term DAPT is associated with similar rates of MACE but lower risk of bleeding when as compared with prolonged DAPT. There was no significant difference between sexes in the population studied. © 2016 Wiley Periodicals, Inc.
Publisher: Oxford University Press (OUP)
Date: 07-11-2022
DOI: 10.1093/EURHEARTJ/EHAC395
Abstract: Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk lification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin–angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
DOI: 10.1161/HYPERTENSIONAHA.121.17736
Abstract: A U-shaped association between serum potassium (s-potassium) and short-term mortality has been reported for patients with hypertension. Less is known about the long-term prognostic implications of s-potassium and whether this relationship is modified by intensive blood pressure (BP) control. SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized, controlled trial of 9361 high-risk patients aged ≥50 years without diabetes, who were allocated to intensive versus standard BP control. We investigated associations between baseline and on-treatment s-potassium and death, using Cox proportional hazards regression (including s-potassium as a time-dependent covariate) and restricted cubic splines. We further explored the effects of intensive BP control across the s-potassium spectrum. Baseline s-potassium was available in 9336 in iduals, and 8473 had a measurement at 12 months. Mean baseline s-potassium was similar between the 2 treatment groups (intensive 4.21 mmol/L versus standard 4.20 mmol/L P =0.74), but on-treatment s-potassium was lower in the intensive group (4.14 mmol/L versus 4.18 mmol/L P =0.001). Median follow-up was 3.3 years, with 365 all-cause deaths (3.9%) and 102 cardiovascular deaths (1.1%). Baseline s-potassium had a linear association with both types of death events ( P .05). On-treatment potassium also had a linear association with all-cause death ( P =0.04) but not with cardiovascular death ( P =0.13). None of the associations remained significant after multivariable adjustment ( P ≥0.05). S-potassium did not modify the effect of intensive BP control ( P ≥0.05). In SPRINT, neither baseline nor on-treatment s-potassium levels were independently associated with death, and the effect of intensive BP control was not modified by s-potassium. Careful monitoring of patients on antihypertensive medications may eliminate the risks associated with abnormal s-potassium. URL: www.clinicaltrials.gov Unique identifier: NCT01206062
Publisher: Wiley
Date: 18-05-2017
DOI: 10.1002/CLC.22721
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.HLC.2018.04.292
Abstract: Compared with other manifestations of cardiovascular disease, peripheral arterial disease (PAD) is under-diagnosed. This study aims to investigate the prevalence, risk profile and cardiovascular outcomes of undiagnosed PAD in Australian general practices. A sub-study of the Australian Reduction of Atherothrombosis for Continued Health (REACH) Registry, a prospective cohort study of patients at high risk of atherothrombosis recruited from Australian general practices. Eligible patients for this study had no previous clinical diagnosis of PAD and had an ankle-brachial index (ABI) ≤1.4 at recruitment. Peripheral arterial disease was undiagnosed in 34% Australian REACH participants, 28% patients had low ABI (ABI<0.9) and 11% had intermittent claudication (IC) based on responses to the Edinburgh Claudication Questionnaire (ECQ). We found no significant differences in risk factor control between patient with or without PAD. Intermittent claudication patients had higher risks of non-fatal cardiovascular events and PAD interventions at one year, whereas all-cause mortality rate was higher among patients with ABI<0.9, especially in those who also reported IC. Finally, an ABI<0.9, together with poorly controlled risk factors were independent predictors of incident IC at one year. This study suggests a high rate of undiagnosed PAD among high risk patients in Australian primary health care. These patients are at high risk of events and therefore would potentially benefit from better secondary prevention measures.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JACC.2018.10.039
Abstract: The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths. This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES. Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death. With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk. In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.CLINTHERA.2011.08.004
Abstract: Although few cardiovascular registries report the costs of illness or cost-effectiveness of health interventions, such information is critical to inform the effective and cost-effective management of cardiovascular disease, particularly if drawn from population-based registries, which more accurately reflect clinical practice and follow up patients for much longer than clinical trials. The goal of this study was to estimate the cost-effectiveness of closing the statin "treatment gap" in the secondary prevention of coronary artery disease (CAD) in Australia. A decision analysis Markov model was developed with yearly cycles and the health states of alive or dead. Using data from the Australian Reduction of Atherothrombosis for Continued Health Registry, the model compared current statin coverage (82%) in the secondary prevention of CAD (the current group) with a hypothetical situation of 100% coverage (the improved group). The 18% gap was filled with use of generic statins. Data from a recent meta-analysis were used to estimate the benefits of statin use in terms of reducing recurrent cardiovascular events and death. Government reimbursement data from 2011 were used to calculate direct health care costs. The cost of the intervention to improve statin coverage was assumed to be $250 per person. Years of life lived and costs were discounted at 5% annually. All values are given in Australian dollars. Among the 2058 subjects in the current group, the model estimated that there would be 106 nonfatal myocardial infractions, 68 nonfatal strokes, and 275 deaths over 5 years. In the improved group, all of whom took statins, the corresponding numbers were 101, 65, and 259, equating to numbers needed to treat of 426, 639, and 127, respectively. Over the 5 years, there would be 0.018 life-years gained (discounted) at a net cost of $546 (discounted) per person. These equated to an incremental cost-effectiveness ratio of $29,717 per life-year gained. The results suggest that for patients with CAD, maximizing coverage with statins, in line with evidence-based recommendations, represents a cost-effective means of secondary prevention.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.HLC.2013.02.002
Abstract: To report on two-year cardiovascular (CV) event rates and quantify the cost of cardiovascular disease using the Australian Reduction of Atherothrombosis for Continued Health (REACH) registry. Prospective registry of 2873 patients with multiple risk factors (MRF), coronary artery disease (CAD), cerebrovascular disease (CerVD) and peripheral artery disease (PAD), recruited through 273 Australian general practitioners. Government reimbursement data from 2011 was used to calculate direct health care costs (pharmaceuticals, outpatient and hospitalisation costs). The main outcome of interest was two-year rates and associated excess costs of cardiovascular death, myocardial infarction, stroke, and hospitalisation for cardiovascular procedures. The two year follow-up data were available for 2856 (99.4%) patients. Incidence of any hospitalisation and cardiovascular death was highest among those with previous history of PAD at baseline 49% (n=126), and 5.1% (n=13). Non-fatal cardiovascular events were highest among the PAD and CAD groups (21.8% (n=56) and 14.1% (n=297) respectively). Those with previous history of PAD and CerVD at baseline had the highest likelihood of CV death (OR=2.53 (95% CI: 1.58-4.08) and OR=1.61 (1.05-2.46) respectively) in comparison to other groups. Patients with PAD had the highest likelihood of vascular interventions OR=3.11 (95% CI: 2.09-4.63) at two years. Overall, the mean (SD) direct expenditure over two years of follow-up per person was A$7544 (A$10,758). In the adjusted model, patients with CAD and PAD incurred A$1093 (95% CI A$24 - A$2072) and A$4890 (95% CI A$3105 - A$6869) more in mean total costs compared to patients with MRF. Patients with PAD had the highest likelihood of vascular interventions and CV death, and incurred high excess costs in comparison to other groups.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-02-2019
DOI: 10.1161/CIRCULATIONAHA.118.035864
Abstract: Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies). We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups. Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152). Patients who required anticoagulation or had a stroke within 1 month, previous lacunar stroke, or intracerebral hemorrhage were excluded. During a mean follow-up of 23 months, fewer patients had strokes in the rivaroxaban plus aspirin group than in the aspirin group (83 [0.9% per year] versus 142 [1.6% per year] hazard ratio [HR], 0.58 95% CI, 0.44–0.76 P .0001). Ischemic/uncertain strokes were reduced by nearly half (68 [0.7% per year] versus 132 [1.4% per year] HR, 0.51 95% CI, 0.38–0.68 P .0001) by the combination in comparison with aspirin. No significant difference was noted in the occurrence of stroke in the rivaroxaban alone group in comparison with aspirin: annualized rate of 0.7% (HR, 0.82 95% CI, 0.65–1.05). The occurrence of fatal and disabling stroke (modified Rankin Scale, 3–6) was decreased by the combination (32 [0.3% per year] versus 55 [0.6% per year] HR, 0.58 95% CI, 0.37–0.89 P =0.01). Independent predictors of stroke were prior stroke, hypertension, systolic blood pressure at baseline, age, diabetes mellitus, and Asian ethnicity. Prior stroke was the strongest predictor of incident stroke (HR, 3.63 95% CI, 2.65–4.97 P .0001) and was associated with a 3.4% per year rate of stroke recurrence on aspirin. The effect of the combination in comparison with aspirin was consistent across subgroups with high stroke risk, including those with prior stroke. Low-dose rivaroxaban plus aspirin is an important new antithrombotic option for primary and secondary stroke prevention in patients with clinical atherosclerosis. URL: www.clinicaltrials.gov . Unique identifier: NCT01776424.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1053/J.GASTRO.2019.04.041
Abstract: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52 95% confidence interval, 0.28-0.94 P = .03) this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982 95% confidence interval, 609-2528). In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
Publisher: Elsevier BV
Date: 09-2022
Publisher: SAGE Publications
Date: 30-07-2018
Abstract: Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a s le of consenting COMPASS participants without contraindications to MRI. COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in in iduals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy biomarker and genetic s les at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study. Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23–28). The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.
Publisher: MDPI AG
Date: 09-2018
Abstract: Migrants from hepatitis B virus (HBV) endemic countries to the European Union/European Economic Area (EU/EEA) comprise 5.1% of the total EU/EEA population but account for 25% of total chronic Hepatitis B (CHB) infection. Migrants from high HBV prevalence regions are at the highest risk for CHB morbidity. These migrants are at risk of late detection of CHB complications mortality and onwards transmission. The aim of this systematic review is to evaluate the effectiveness and cost-effectiveness of CHB screening and vaccination programs among migrants to the EU/EEA. We found no RCTs or direct evidence evaluating the effectiveness of CHB screening on morbidity and mortality of migrants. We therefore used a systematic evidence chain approach to identify studies relevant to screening and prevention programs testing, treatment, and vaccination. We identified four systematic reviews and five additional studies and guidelines that reported on screening and vaccination effectiveness. Studies reported that vaccination programs were highly effective at reducing the prevalence of CHB in children (RR 0.07 95% CI 0.04 to 0.13) following vaccination. Two meta-analyses of therapy for chronic HBV infection found improvement in clinical outcomes and intermediate markers of disease. We identified nine studies examining the cost-effectiveness of screening for CHB: a strategy of screening and treating CHB compared to no screening. The median acceptance of HB screening was 87.4% (range 32.3–100%). Multiple studies highlighted barriers to and the absence of effective strategies to ensure linkage of treatment and care for migrants with CHB. In conclusion, screening of high-risk children and adults and vaccination of susceptible children, combined with treatment of CHB infection in migrants, are promising and cost-effective interventions, but linkage to treatment requires more attention.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.JACL.2022.08.004
Abstract: Elevated red blood cell distribution width (RDW) is associated with increased risk for major adverse cardiovascular events (MACE) and death in patients with cardiovascular disease. The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome (ACS) and elevated atherogenic lipoproteins despite optimized statin treatment. This post hoc analysis determined whether RDW independently predicts risk of MACE and death in patients after recent ACS, whether RDW influences MACE reduction with alirocumab, and whether alirocumab treatment affects RDW. Associations of baseline RDW with risk of MACE and death were analyzed in the placebo group in adjusted proportional hazards models. Interactions of RDW and treatment on the risk of MACE and death were evaluated. An increasing quartile of RDW was associated with characteristics that predicted risk of MACE and death including age, hypertension, diabetes, atherosclerotic conditions and events, revascularizations, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. After adjusting for baseline characteristics associated with the risk of MACE or death, baseline RDW remained independently associated with the risk of MACE and death in the placebo group (hazard ratios [95% confidence intervals] 1.08 [1.02-1.15] and 1.13 [1.03-1.24] per 1% increase of RDW, respectively, both p <0.001). There was no interaction of RDW and treatment on MACE or death, nor did alirocumab affect RDW. RDW was associated with an increased risk of MACE and death, independent of established risk factors.
Publisher: Massachusetts Medical Society
Date: 24-01-2019
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.AMJMED.2012.01.014
Abstract: Prediction models for cardiovascular events and cardiovascular death in patients with established cardiovascular disease are not generally available. Participants from the prospective REduction of Atherothrombosis for Continued Health (REACH) Registry provided a global outpatient population with known cardiovascular disease at entry. Cardiovascular prediction models were estimated from the 2-year follow-up data of 49,689 participants from around the world. A developmental prediction model was estimated from 33,419 randomly selected participants (2394 cardiovascular events with 1029 cardiovascular deaths) from the pool of 49,689. The number of vascular beds with clinical disease, diabetes, smoking, low body mass index, history of atrial fibrillation, cardiac failure, and history of cardiovascular event(s) <1 year before baseline examination increased risk of a subsequent cardiovascular event. Statin (hazard ratio 0.75 95% confidence interval, 0.69-0.82) and acetylsalicylic acid therapy (hazard ratio 0.90 95% confidence interval, 0.83-0.99) also were significantly associated with reduced risk of cardiovascular events. The prediction model was validated in the remaining 16,270 REACH subjects (1172 cardiovascular events, 494 cardiovascular deaths). Risk of cardiovascular death was similarly estimated with the same set of risk factors. Simple algorithms were developed for prediction of overall cardiovascular events and for cardiovascular death. This study establishes and validates a risk model to predict secondary cardiovascular events and cardiovascular death in outpatients with established atherothrombotic disease. Traditional risk factors, burden of disease, lack of treatment, and geographic location all are related to an increased risk of subsequent cardiovascular morbidity and cardiovascular mortality.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.JACC.2007.03.025
Abstract: The purpose of this study was to determine the possible benefit of dual antiplatelet therapy in patients with prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease (PAD). Dual antiplatelet therapy with clopidogrel plus aspirin has been validated in the settings of acute coronary syndromes and coronary stenting. The value of this combination was recently evaluated in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial, where no statistically significant benefit was found in the overall broad population of stable patients studied. We identified the subgroup in the CHARISMA trial who were enrolled with documented prior MI, ischemic stroke, or symptomatic PAD. A total of 9,478 patients met the inclusion criteria for this analysis. The median duration of follow-up was 27.6 months. The rate of cardiovascular death, MI, or stroke was significantly lower in the clopidogrel plus aspirin arm than in the placebo plus aspirin arm: 7.3% versus 8.8% (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01). Additionally, hospitalizations for ischemia were significantly decreased, 11.4% versus 13.2% (HR 0.86, 95% CI 0.76 to 0.96, p = 0.008). There was no significant difference in the rate of severe bleeding: 1.7% versus 1.5% (HR 1.12, 95% CI 0.81 to 1.53, p = 0.50) moderate bleeding was significantly increased: 2.0% versus 1.3% (HR 1.60, 95% CI 1.16 to 2.20, p = 0.004). In this analysis of the CHARISMA trial, the large number of patients with documented prior MI, ischemic stroke, or symptomatic PAD appeared to derive significant benefit from dual antiplatelet therapy with clopidogrel plus aspirin. Such patients may benefit from intensification of antithrombotic therapy beyond aspirin alone, a concept that future trials will need to validate. (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA] t/show/NCT00050817?order=1 NCT00050817).
Publisher: BMJ
Date: 10-03-2011
Abstract: This study investigated the effect of clopidogrel treatment on inflammatory activity as evidenced by the change in high-sensitivity C-reactive protein (hsCRP) levels in a broad population of patients who are at high risk of atherothrombotic events. The predictive value of hsCRP levels for a treatment benefit of clopidogrel was also explored. The study included 8021 patients with established atherosclerotic disease or multiple cardiovascular risk factors enrolled in the CHARISMA trial. Patients were randomly assigned either to clopidogrel plus aspirin or placebo plus aspirin. HsCRP was measured at study entry and at study termination (median 28&emsp14 months). The predefined primary composite endpoint was myocardial infarction, stroke, or death from cardiovascular causes. There was a stepwise increase in the event rate of the combined primary endpoint with increasing quartiles of hsCRP at baseline (4.0%, 6.1%, 7.4% and 8.7% for the highest quartile). In both treatment groups the changes in hsCRP levels over time were identical. In patients with low hsCRP levels (<3 mg/l) clopidogrel treatment was associated with a lower event rate compared with placebo (4.0% vs 6.0%, log rank p=0.005). In contrast no treatment effect was observed in patients with high hsCRP levels (8.1% vs 8.0%, ns). In this broad population, hsCRP is a powerful predictor of ischaemic events. Compared with placebo, clopidogrel was without effect on inflammatory markers. The reduction in cardiovascular events by antiplatelet treatment with clopidogrel was isolated to patients with low levels of hsCRP.
Publisher: American Medical Association (AMA)
Date: 17-04-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-10-2008
DOI: 10.1161/CIRCULATIONAHA.108.768283
Abstract: Background— Incomplete inhibition of platelet thromboxane generation, as measured by elevated urinary 11-dehydro thromboxane B 2 concentrations, has been associated with an increased risk of cardiovascular events. We aimed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B 2 concentrations that could thereby reduce cardiovascular risk. Methods and Results— Urinary 11-dehydro thromboxane B 2 concentrations were measured in 3261 aspirin-treated patients at least 1 month after they had been randomly assigned to placebo or clopidogrel. Baseline urinary 11-dehydro thromboxane B 2 concentrations in the highest quartile were associated with an increased risk of stroke, myocardial infarction, or cardiovascular death compared with the lowest quartile (adjusted hazard ratio 1.66, 95% CI 1.06 to 2.61, P =0.03). Increasing age, female sex, history of peripheral artery disease, current smoking, and oral hypoglycemic or angiotensin-converting enzyme inhibitor therapy were independently associated with higher urinary concentrations of 11-dehydro thromboxane B 2 , whereas aspirin dose ≥150 mg/d, history of treatment with nonsteroidal antiinflammatory drugs, history of hypercholesterolemia, and statin treatment were associated with lower concentrations. Randomization to clopidogrel (versus placebo) did not reduce the hazard of cardiovascular events in patients in the highest quartile of urinary 11-dehydro thromboxane B 2 levels. Conclusions— In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B 2 are an externally valid and potentially modifiable determinant of stroke, myocardial infarction, or cardiovascular death in patients at risk for atherothrombotic events.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2020
DOI: 10.1161/STROKEAHA.120.029762
Abstract: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4% hazard ratio [95% CI], 0.51 [0.38–0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37–1.60]) Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27–1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. URL: www.clinicaltrials.gov . Unique identifier: NCT01776424.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Oxford University Press (OUP)
Date: 06-07-2023
Abstract: Low-dose colchicine reduces cardiovascular risk in patients with coronary artery disease (CAD), but absolute benefits may vary between in iduals. This study aimed to assess the range of in idual absolute benefits from low-dose colchicine according to patient risk profile. The European Society of Cardiology (ESC) guideline–recommended SMART-REACH model was combined with the relative treatment effect of low-dose colchicine and applied to patients with CAD from the Low-Dose Colchicine 2 (LoDoCo2) trial and the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease (UCC-SMART) study (n = 10 830). In idual treatment benefits were expressed as 10-year absolute risk reductions (ARRs) for myocardial infarction, stroke, or cardiovascular death (MACE), and MACE-free life-years gained. Predictions were also performed for MACE plus coronary revascularization (MACE+), using a new lifetime model derived in the REduction of Atherothrombosis for Continued Health (REACH) registry. Colchicine was compared with other ESC guideline–recommended intensified (Step 2) prevention strategies, i.e. LDL cholesterol (LDL-c) reduction to 1.4 mmol/L and systolic blood pressure (SBP) reduction to 130 mmHg. The generalizability to other populations was assessed in patients with CAD from REACH North America and Western Europe (n = 25 812). The median 10-year ARR from low-dose colchicine was 4.6% [interquartile range (IQR) 3.6–6.0%] for MACE and 8.6% (IQR 7.6–9.8%) for MACE+. Lifetime benefit was 2.0 (IQR 1.6–2.5) MACE-free years, and 3.4 (IQR 2.6–4.2) MACE+-free life-years gained. For LDL-c and SBP reduction, respectively, the median 10-year ARR for MACE was 3.0% (IQR 1.5–5.1%) and 1.7% (IQR 0.0–5.7%), and the lifetime benefit was 1.2 (IQR 0.6–2.1) and 0.7 (IQR 0.0–2.3) MACE-free life-years gained. Similar results were obtained for MACE+ and in American and European patients from REACH. The absolute benefits of low-dose colchicine vary between in idual patients with chronic CAD. They may be expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in a majority of patients already on conventional lipid-lowering and blood pressure–lowering therapy.
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 05-04-2018
DOI: 10.2807/1560-7917.ES.2018.23.14.17-00543
Abstract: Migrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 in idual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rif icin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest in idual and public health benefit.
Publisher: Oxford University Press (OUP)
Date: 25-06-2018
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 05-04-2018
DOI: 10.2807/1560-7917.ES.2018.23.14.17-00542
Abstract: : The foreign-born population make up an increasing and large proportion of tuberculosis (TB) cases in European Union/European Economic Area (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods : We conducted a systematic review to determine effectiveness (yield and performance of chest radiography (CXR) to detect active TB, treatment outcomes and acceptance of screening) and a second systematic review on cost-effectiveness of screening for active TB among migrants living in the EU/EEA. Results : We identified six systematic reviews, one report and three in idual studies that addressed our aims. CXR was highly sensitive (98%) but only moderately specific (75%). The yield of detecting active TB with CXR screening among migrants was 350 per 100,000 population overall but ranged widely by host country (110–2,340), migrant type (170–1,192), TB incidence in source country (19–336) and screening setting (220–1,720). The CXR yield was lower (19.6 vs 336/100,000) and the numbers needed to screen were higher (5,076 vs 298) among migrants from source countries with lower TB incidence (≤ 50 compared with ≥ 350/100,000). Cost-effectiveness was highest among migrants originating from high ( 120/100,000) TB incidence countries. The foreign-born had similar or better TB treatment outcomes than those born in the EU/EEA. Acceptance of CXR screening was high (85%) among migrants. Discussion : Screening programmes for active TB are most efficient when targeting migrants from higher TB incidence countries. The limited number of studies identified and the heterogeneous evidence highlight the need for further data to inform screening programmes for migrants in the EU/EEA.
Publisher: Massachusetts Medical Society
Date: 03-01-2019
Publisher: Oxford University Press (OUP)
Date: 14-10-2020
DOI: 10.1093/EURHEARTJ/EHAA649
Abstract: Lipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events. Cardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio P trend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median −5.0 [−13.6, 0] mg/dL) and corrected LDL-C (median −51.3 [−67.1, −34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events. Baseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-05-2011
DOI: 10.1161/CIRCULATIONAHA.110.000786
Abstract: Atopaxar (E5555) is a reversible protease-activated receptor-1 thrombin receptor antagonist that interferes with platelet signaling. The primary objective of the Lessons From Antagonizing the Cellular Effects of Thrombin–Acute Coronary Syndromes (LANCELOT—ACS) trial was to evaluate the safety and tolerability of atopaxar in patients with ACS. Six hundred and three subjects were randomized within 72 hours of non–ST-elevation ACS to 1 of 3 doses of atopaxar (400-mg loading dose followed by 50, 100, or 200 mg daily) or matching placebo. The incidence of Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) major or minor bleeding did not differ significantly between the combined atopaxar and placebo groups (3.08% versus 2.17%, respectively P =0.63), and there was no dose-related trend ( P =0.80). The incidence of CURE major bleeding was numerically higher in the atopaxar group compared with the placebo group (1.8% versus 0% P =0.12). The incidence of cardiovascular death, myocardial infarction, stroke, or recurrent ischemia was similar between the atopaxar and placebo arms (8.03% versus 7.75% P =0.93). The incidence of CV death, MI, or stroke was 5.63% in the placebo group and 3.25% in the combined atopaxar group ( P =0.20). Dose-dependent trends for efficacy were not seen. Atopaxar significantly reduced ischemia on continuous ECG monitoring (Holter) at 48 hours compared with placebo (relative risk, 0.67 P =0.02). Transient dose-dependent transaminase elevation and relative QTc prolongation were observed with the highest doses of atopaxar. In patients after ACS, atopaxar significantly reduced early ischemia on Holter monitoring without a significant increase in major or minor bleeding. Larger trials are required to fully establish the efficacy and safety of atopaxar. URL: www.ClinicalTrials.gov . Unique identifier: NCT00548587.
Publisher: MDPI AG
Date: 09-08-2018
Abstract: Migrants, defined as in iduals who move from their country of origin to another, account for 40% of newly-diagnosed cases of human immunodeficiency virus (HIV) in the European Union/European Economic Area (EU/EEA). Populations at high risk for HIV include migrants, from countries or living in neighbourhoods where HIV is prevalent, and those participating in high risk behaviour. These migrants are at risk of low CD4 counts at diagnosis, increased morbidity, mortality, and onward transmission. The aim of this systematic review is to evaluate the effectiveness and cost-effectiveness of HIV testing strategies in migrant populations and to estimate their effect on testing uptake, mortality, and resource requirements. Following a systematic overview, we included four systematic reviews on the effectiveness of strategies in non-migrant populations and inferred their effect on migrant populations, as well as eight in idual studies on cost-effectiveness/resource requirements. We assessed the certainty of our results using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The systematic reviews reported that HIV tests are highly accurate (rapid test % sensitivity, Western blot and ELISA % sensitivity). A meta-analysis showed that rapid testing approaches improve the access and uptake of testing (risk ratio = 2.95, 95% CI: 1.69 to 5.16), and were associated with a lower incidence of HIV in the middle-aged women subgroup among marginalised populations at a high risk of HIV exposure and HIV related stigma. Economic evidence on rapid counselling and testing identified strategic advantages with rapid tests. In conclusion, community-based rapid testing programmes may have the potential to improve uptake of HIV testing among migrant populations across a range of EU/EEA settings.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
DOI: 10.1161/CIRCOUTCOMES.119.005858
Abstract: In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18 924 patients. Alirocumab reduced first occurrence of the primary composite end point—coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina—as well as total nonfatal cardiovascular events and all-cause deaths. The present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. In prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16 629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92–1.00] P =0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000–1.007] P =0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728–0.986] P =0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00–1.13] P =0.03). Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome. URL: www.clinicaltrials.gov . Unique identifier: NCT01663402.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.AHJ.2008.08.031
Abstract: Atherothrombosis is a common condition affecting in iduals worldwide. Its impact on different ethnic groups receiving evidence-based therapy is unclear. We aimed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy. This was a prospective observational study of 15,603 patients enrolled in the CHARISMA trial followed up every 6 months for a median of 28 months. The primary efficacy end point was the first occurrence of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was bleeding. The cohort comprised 12,502 (80.1%) white, 486 (3.1%) black, 775 (5.0%) Asian, and 1,613 (10.3%) Hispanic patients. There was no difference in the occurrence of the primary composite end point among the 4 ethnic groups. Compared with Asians, cardiovascular and all-cause mortality occurred more frequently among black (adjusted hazard 2.19 and 2.04) and Hispanic (adjusted hazard, 1.83 and 1.69) patients. Although the occurrence of severe bleeding was similarly low among the 4 ethnic groups, Asian (adjusted hazard, 2.21) and black (adjusted hazard, 3.06) patients were more likely to have moderate bleeding complications than Hispanic patients. In this trial of in iduals at risk of vascular events, ethnicity was not a significant, independent predictor of the primary composite cardiovascular event. However, ethnicity was a significant, independent predictor of the secondary outcomes, cardiovascular and all-cause mortality (blacks and Hispanics), and moderate bleeding complications (blacks and Asians).
Publisher: Elsevier BV
Date: 06-2006
DOI: 10.1016/J.AHJ.2005.08.011
Abstract: Restenosis after percutaneous coronary intervention (PCI) has been thought to present in a stable manner as exertional angina. However, the presentation of in-stent restenosis (ISR) is not well-studied. We hypothesized that a substantial proportion of bare metal ISR presents as acute coronary syndromes. We aimed to characterize the severity of the clinical presentation of ISR. We searched our PCI database for all cases of PCI for bare metal ISR occurring between May 1999 and September 2003. Multivessel interventions were excluded. In-stent restenosis presentation was classified into three categories: (1) myocardial infarction (MI), (2) unstable angina requiring hospitalization before angiography, and (3) exertional angina. Routine angiographic screening after initial stent placement was not performed, so ISR episodes were clinical, rather than angiographic, ISR. We identified 1186 cases of bare metal ISR in 984 patients. Median age was 63, 72% were male, and 36% had diabetes. Of the ISR episodes, 9.5% presented as acute MI (7.3% as non-ST-segment elevation MI and 2.2% as ST-segment elevation MI), 26.4% as unstable angina requiring hospitalization before angiography, and 64.1% as exertional angina. More than one third of bare metal ISR episodes presented as MI or unstable angina requiring hospitalization. The acuity of the clinical presentation of bare metal ISR appears to be more severe than has been previously thought. Aggressive efforts, such as drug-eluting stents to decrease the incidence of unstable angina due to bare metal ISR, are warranted.
Publisher: AMPCo
Date: 02-2012
DOI: 10.5694/MJA11.10731
Abstract: To report on 1-year cardiovascular (CV) event rates in patients with established cardiovascular disease (CVD) or with multiple cardiovascular risk factors. Prospective cohort study of 2873 patients at high risk of atherothrombosis based on the presence of multiple risk factors and overt coronary artery disease (CAD), cerebrovascular disease (CerVD) or peripheral arterial disease (PAD) presenting to 273 Australian general practitioners this study was conducted as part of the international REACH Registry. One-year rates of cardiovascular death, myocardial infarction, stroke, and hospitalisation for cardiovascular procedures. The cardiovascular death rate at 1 year was 1.4%. The combined cardiovascular death, non-fatal MI, stroke and hospitalisation rate for vascular disease affecting one location at 1 year was 11%. Even for patients with no overt disease, but with multiple risk factors, the 1-year combined event rate was 4.2%. The highest combined event rate was in patients with PAD (21.0%), and in patients with atherothrombotic disease identified in all three locations (coronary arteries, cerebrovascular system and peripheral arteries) at 39%. The rate of clinical events in community-based patients with stable atherothrombotic disease increases dramatically with the severity of disease and the number of vascular beds involved. Where disease was evident in all three locations, and for patients with PAD alone, the 1-year risk of cardiovascular events was substantially increased. Poor adherence to statin therapy in the secondary preventive setting is a major treatment gap that needs to be closed the influences of obesity and diabetes warrant further investigation.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2014
DOI: 10.1161/CIRCINTERVENTIONS.114.001506
Abstract: In selected patients with hypertension, renal artery (RA) stenting is used to treat significant atherosclerotic stenoses. However, blood pressure often remains uncontrolled after the procedure. Although catheter-based renal denervation (RDN) can reduce blood pressure in certain patients with resistant hypertension, there are no data on the feasibility and safety of RDN in stented RA. We report marked blood pressure reduction after RDN in a patient with resistant hypertension who underwent previous stenting. Subsequently, radiofrequency ablation was investigated within the stented segment of porcine RA, distal to the stented segment, and in nonstented RA and compared with stent only and untreated controls. There were neither observations of thrombus nor gross or histological changes in the kidneys. After radiofrequency ablation of the nonstented RA, sympathetic nerves innervating the kidney were significantly reduced, as indicated by significant decreases in sympathetic terminal axons and reduction of norepinephrine in renal tissue. Similar denervation efficacy was found when RDN was performed distal to a renal stent. In contrast, when radiofrequency ablation was performed within the stented segment of the RA, significant sympathetic nerve ablation was not seen. Histological observation showed favorable healing in all arteries. Radiofrequency ablation of previously stented RA demonstrated that RDN provides equally safe experimental procedural outcomes in a porcine model whether the radiofrequency treatment is delivered within, adjacent, or without the stent struts being present in the RA. However, efficacious RDN is only achieved when radiofrequency ablation is delivered to the nonstented RA segment distal to the stent.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JACC.2019.03.013
Abstract: Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined. This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8% the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402).
Publisher: Wiley
Date: 07-2011
DOI: 10.1111/J.1755-5922.2011.00291.X
Abstract: To describe aspirin use in primary and secondary prevention and to determine the incremental costs-effectiveness ratio (ICER) per life year gain (LYG) of aspirin use among subjects with, or at high risk of atherothrombotic disease. To project the cost-effectiveness of aspirin over 5 years of follow-up, a Markov state transition model was developed with yearly cycles and the following health states: "Alive" (post-CAD) and "Dead." The model compared current coverage observed among 2361 subjects using the prospective Australian subset of Reduction of Atherothrombosis for continued Health (REACH) registry, and hypothetical situation whereby all subjects assumed to be treated. Costs were calculated based on the Australian government reimbursed data for 2010. ICER per LYG for increased use of aspirin. The use of aspirin in current group varied from 67% to 70%. The base-case analysis showed that increasing aspirin use among subjects with existing CAD in outpatient settings was cost saving, while increasing use of aspirin in primary prevention equated to an ICER of AUD 7126 per LYG. Among subjects with existing CAD aspirin use was shown to be a dominant choice of treatment. However, among patients without existing cardiovascular disease (primary prevention), increased uptake of aspirin was cost effective but with uncertain benefit, with two hemorrhagic bleeding events occurring for every life saved.
Publisher: Oxford University Press (OUP)
Date: 09-11-2022
DOI: 10.1093/CID/CIAC455
Abstract: Halting transmission of Mycobacterium tuberculosis (Mtb) by identifying infectious in iduals early is key to eradicating tuberculosis (TB). Here we evaluate face mask s ling as a tool for stratifying the infection risk of in iduals with pulmonary TB (PTB) to their household contacts. Forty-six sputum-positive PTB patients in The Gambia (August 2016–November 2017) consented to mask s ling prior to commencing treatment. Incident Mtb infection was defined in 181 of their 217 household contacts as QuantiFERON conversion or an increase in interferon-γ of ≥1 IU/mL, 6 months after index diagnosis. Multilevel mixed-effects logistical regression analysis with cluster adjustment by household was used to identify predictors of incident infection. Mtb was detected in 91% of PTB mask s les with high variation in IS6110 copies (5.3 × 102 to 1.2 × 107). A high mask Mtb level (≥20 000 IS6110 copies) was observed in 45% of cases and was independently associated with increased likelihood of incident Mtb infection in contacts (adjusted odds ratio, 3.20 [95% confidence interval, 1.26–8.12] P = .01), compared with cases having low-positive/negative mask Mtb levels. Mask Mtb level was a better predictor of incident Mtb infection than sputum bacillary load, chest radiographic characteristics, or sleeping proximity. Mask s ling offers a sensitive and noninvasive tool to support the stratification of in iduals who are most infectious in high-TB-burden settings. Our approach can provide better insight into community transmission in complex environments.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-10-2021
DOI: 10.1161/CIRCULATIONAHA.121.056810
Abstract: The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial. In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months. Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59–2.79] P =0.53). PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. URL: www.clinicaltrials.gov Unique identifier: NCT02663908.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-11-2019
DOI: 10.1161/CIRCULATIONAHA.119.042551
Abstract: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non−high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category. Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR hazard ratio=0.86 for not VHR P interaction =0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions P interaction =0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8% P interaction =0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8% P interaction =0.661). The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab. URL: www.clinicaltrials.gov . Unique identifier: NCT01663402.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2010
DOI: 10.1161/STROKEAHA.110.586727
Abstract: Background and Purpose— Disabling stroke is costly and considered by some patients a fate worse than death. We aimed to determine whether clopidogrel reduces the rate and functional severity of stroke among high vascular risk patients, including patients with previous transient ischemic attack or ischemic stroke, who were enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial. Methods— We randomly assigned 15 603 high vascular risk patients to receive clopidogrel (75 mg daily) or placebo in addition to background acetylsalicylic acid and followed them for a median of 28 months. The main outcome of this prespecified substudy was the functional severity of stroke outcome events as measured by the modified Rankin Scale (mRS) score at 3 months after the stroke outcome. Results— During follow-up, 436 (2.8%) patients had a definite adjudicated stroke and a follow-up assessment of the mRS at 3 months poststroke, of whom 202 had been randomly assigned clopidogrel and 234 placebo (relative risk reduction 14%, 95% CI: −4% to 29%, P =0.12). There was no significant difference between the mean mRS scores at 3 months after stroke among patients assigned clopidogrel compared with placebo (mean mRS 3.6 [SD 2.4] clopidogrel versus 3.3 [SD 2.1] placebo P =0.15). There was also no significant difference between the various categories of the mRS score at 3 months after stroke among patients assigned to clopidogrel compared with placebo. Among 4320 patients with a qualifying diagnosis of transient ischemic attack or ischemic stroke, 233 (5.4%) experienced a stroke during follow-up, of whom 103 were randomly assigned clopidogrel and 130 placebo (relative risk reduction 20%, 95% CI: −3% to 38%). There was no significant difference between the mean mRS scores at 3 months after stroke among patients with a qualifying transient ischemic attack or ischemic stroke who were assigned clopidogrel compared with placebo (3.4 [SD 2.1] clopidogrel versus 3.3 [SD 1.9] placebo P =0.48). Conclusion— The addition of clopidogrel to acetylsalicylic acid did not significantly alter the rate and functional severity of stroke outcome events among high vascular risk patients enrolled in the CHARISMA trial.
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.AHJ.2011.11.001
Abstract: There is a clinical need for an intravenous P2Y(12) inhibitor in patients with acute coronary syndromes (ACS) for patients who are unable to take oral medications or might benefit from a rapidly reversible compound. As the time from admission to percutaneous coronary intervention (PCI) shortens, establishing the benefit of novel therapies impacting ischemic events is increasingly challenging. Cangrelor, an intravenous potent rapidly acting P2Y(12) inhibitor, bolus 30 μg/Kg plus infusion of 4 μg/Kg/min, was compared to a 600-mg loading dose of clopidogrel either before or early after PCI in patients with ACS undergoing PCI in The CHAMPION (Cangrelor versus standard tHerapy to Achieve optimal Management of Platelet InhibitiON) PLATFORM and PCI studies. As both CHAMPION studies used similar inclusion/exclusion criteria and death, myocardial infarction, or ischemia-driven revascularization (including stent thrombosis) at 48 hours as their primary end points, the studies were pooled. The clinical events committee adjudicated myocardial infarction. The universal definition was used to define myocardial infarction. A total of 13 049 patients were included. Cangrelor had no effect on the primary end point with the original MI definition (P = .646). With the use of the universal definition, the primary end point was decreased with cangrelor (odds ratio 0.82, 95% confidence interval 0.68-0.99, P = .037). Stent thrombosis was reduced from 0.4% to 0.2% (odds ratio 0.44, 95% confidence interval 0.22-0.87, P = .018). Thrombolysis in Myocardial Infarction major bleeding and transfusions were not increased with cangrelor. With the use of the universal definition of myocardial infarction, cangrelor was associated with a significant reduction in early ischemic events when compared with clopidogrel in patients with non-ST-elevation ACS undergoing PCI.
Publisher: Springer Science and Business Media LLC
Date: 04-2010
DOI: 10.2165/11530670-000000000-00000
Abstract: Cardiovascular disease (CVD) remains a leading cause of death across the world and poses a significant economic burden. Research regarding per-person use and cost of cardiovascular pharmaceuticals in Australia, as well as potential predictors of pharmaceutical costs in populations using the 'bottom up' costing approach, is limited. Previous studies have adopted 'top down' costing approaches and have been based largely on hypothetical ex les and considered only inpatient settings. To determine the distribution of pharmaceutical costs (from a governmental perspective) related to each cardiovascular risk factor for in iduals with, or at high risk of, CVD by analysing data for Australian participants enrolled in the Reduction of Atherothrombosis for Continued Health (REACH) Registry. 2873 participants were recruited for the REACH Registry through 273 general (primary care) practices in Australia. Included among data collected at baseline was a cardiovascular medicines review. Average weighted costs per person were estimated using Government-reimbursed prices (2007). Annual costs were stratified by sex, age, disease group and other co-morbidities. A multivariate linear regression model was utilized to reveal the predictors of the pharmaceutical costs. The average annual median cost of cardiovascular pharmaceuticals per person was Australian dollars ($A)1310. Use of lipid-lowering agents, non-aspirin (acetylsalicylic acid) antiplatelet agents and thiazolidinediones (glitazones) added significantly to the average annual per-person costs. The multivariate regression model showed that the predictors of annual pharmaceutical costs were dyslipidemia (beta coefficient value [marginal annual cost associated with a condition] $A691 p < 0.001), hypertension ($A346 p < 0.001), vascular disease ($A340 p < 0.001), diabetes mellitus ($A298 p < 0.001), and obesity ($A52 p = 0.03). The same predictors, together with sex, were shown to have an impact on the number of medicines used. Among community-based Australians with, or at risk of, CVD, independent drivers of annual cardiovascular pharmaceutical costs are dyslipidemia (which accounts for half of per-person costs), followed by hypertension, established CVD, and diabetes. Obesity also independently adds to the cost of cardiovascular pharmaceuticals in community-based Australians with, or at risk of, CVD.
Publisher: Elsevier BV
Date: 04-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-05-2020
Abstract: A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91 95% CI , 0.76–1.10 P =0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78 95% CI, 0.63–0.98 P =0.031), sudden cardiac death (adjusted HR, 0.98 95% CI, 0.57–1.70 P =0.95), or atrial fibrillation (adjusted odds ratio, 1.07 95% CI, 0.56–2.04 P =0.84). In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias. URL : www.clinicaltrials.gov Unique identifier: NCT 01225562.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-07-2019
DOI: 10.1161/CIRCULATIONAHA.118.038840
Abstract: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85 95% CI, 0.73 to 0.98 P =0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%] HR, 0.88 95% CI, 0.74 to 1.05 P =0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%] HR, 0.77 95% CI, 0.59 to 1.01 P =0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78 95% CI, 0.65 to 0.94 P =0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths ( P .0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events ( P .001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71 95% CI, 0.56 to 0.90 P interaction =0.007). In the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P =0.017 for linear trend). Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. URL: www.clinicaltrials.gov . Unique identifier: NCT01663402.
Publisher: Oxford University Press (OUP)
Date: 04-06-2013
DOI: 10.1093/HMG/DDT177
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-11-2011
DOI: 10.1161/CIRCULATIONAHA.111.055269
Abstract: A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10 95% confidence interval, 0.86–1.41), cohort studies (risk ratio, 0.94 95% confidence interval, 0.81–1.10), or case-control studies (risk ratio, 0.60 95% confidence interval, 0.41–0.88). Substantial statistical heterogeneity was evident for the case-control studies (I 2 =66%, P =0.01), but not for the cohort studies (I 2 =0%, P =0.48) or randomized trials (I 2 =30%, P =0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. We found no evidence that statins were associated with intracerebral hemorrhage if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.
Publisher: SAGE Publications
Date: 04-01-2011
DOI: 10.1111/J.1747-4949.2010.00535.X
Abstract: The Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilisation, Management and Avoidance (CHARISMA) trial reported no statistically significant benefit of adding clopidogrel to acetylsalicylic acid in the long-term management of a broad population of patients with stable vascular disease. However, a subanalysis raised the hypothesis that dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid may be more effective than aspirin in patients with prior ischaemic stroke, myocardial infarction of symptomatic peripheral arterial disease. We aimed to determine whether the possible benefits of clopidogrel plus acetylsalicylic acid in patients with transient ischaemic attack and ischaemic stroke may be ‘front-loaded’, and maximal within the first 30-days of randomisation, without being unduly hazardous. This was a subanalysis of a randomised, double-blind, placebo-controlled trial of clopidogrel vs. placebo, in addition to background therapy with low-dose acetylsalicylic acid (CHARISMA trial), restricted to all patients with transient ischaemic attack or ischaemic stroke. The primary efficacy outcome was stroke, and safety outcome severe bleeding, during the follow-up period. Among all transient ischaemic attack and ischaemic stroke patients randomised to placebo ( n=2163), 131 (6·1%) experienced a stroke during follow-up compared with 105 (4·9%) of 2157 patients assigned clopidogrel (hazard ratio: 0·80, 95% confidence intervals: 0·62–1·03). There was no significant difference in severe bleeding (1·7% placebo vs. 1·9% clopidogrel, hazard ratio: 1·11, 95% confidence intervals: 0·71–1·73). Among all patients randomised within 30-days of their qualifying transient ischaemic attack or ischaemic stroke to placebo ( n=667), 46 (6·9%) experienced a stroke compared with 34 (5·1%) of 664 patients assigned clopidogrel (hazard ratio: 0·74, 0·46–1·16). There was no significant difference in severe bleeding (1·6% placebo vs. 1·4% clopidogrel, hazard ratio: 0·83, 95% confidence intervals: 0·34–2·01). The data are consistent with, but do not prove the hypothesis that early addition of clopidogrel to acetylsalicylic acid in patients with transient ischaemic attack and ischaemic stroke of arterial origin may be more effective and acceptably safe compared with acetylsalicylic acid alone. Adequately powered clinical trials that are dedicated to exploring this hypothesis are needed.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.AMJCARD.2018.06.052
Abstract: Patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) are sometimes treated with medical management alone rather than an invasive strategy. Among those medically managed without revascularization and discharged, a proportion will require revascularization later on, but little is known about this population. In TRILOGY ACS, 9,326 patients with NSTE ACS who were selected for medical management alone were randomized to treatment with prasugrel or clopidogrel and discharged without revascularization. Patient characteristics and ischemic and bleeding outcomes through 30 months were compared between patients who underwent downstream revascularization after the index hospitalization and those who did not. A total of 662 patients (7.1%) underwent later revascularization by percutaneous coronary intervention (73.1%), coronary artery bypass graft surgery (26.4%), or the two (0.5%). Median time to revascularization was 121 days (twenty-fifth, seventy-fifth percentiles: 41, 326). Revascularized patients were younger, more likely to be male, and had higher rates of hyperlipidemia, diabetes mellitus, prior myocardial infarction, and prior revascularization compared with those not revascularized. Europe and North America had the highest rates of revascularization. During the follow-up period, those who underwent revascularization had a higher rate of the composite outcome of cardiovascular death, myocardial infarction, or stroke occurring after revascularization compared with those not revascularized (hazard ratio [HR] 2.73 [95% confidence interval {CI} 2.21 to 3.38], p < 0.001) as well as a higher rate of each of the in idual outcomes. Major bleeding was also higher in those who underwent revascularization (GUSTO severe or life-threatening: HR 2.61 [95% CI 1.02 to 6.67], p = 0.045 TIMI major: HR 2.24 [95% CI 1.12 to 4.48], p = 0.022). There was no evidence that bleeding and ischemic outcomes varied by treatment with clopidogrel versus prasugrel. In conclusion, among patients initially medically managed after NSTE ACS, a small proportion later require revascularization and have a high rate of ischemic and major bleeding outcomes compared with those not requiring downstream revascularization.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JACC.2016.03.524
Abstract: Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663 19.3% vs. 8.4% p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60 95% confidence interval: 1.20 to 2.13 p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65 95% confidence interval: 0.44 to 0.95 p = 0.026). Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54] NCT01225562).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-05-2011
DOI: 10.1161/CIRCULATIONAHA.110.001404
Abstract: Thrombin is a key mediator of platelet activation. Atopaxar is a reversible protease-activated receptor-1 antagonist that interferes with thrombin-mediated platelet effects. The phase II Lessons From Antagonizing the Cellular Effect of Thrombin–Coronary Artery Disease (LANCELOT–CAD) trial examined the safety and tolerability of prolonged therapy with atopaxar in subjects with CAD. Subjects with a qualifying history were randomized in a double-blind fashion to 3 dosing regimens of atopaxar (50, 100, or 200 mg daily) or matching placebo for 24 weeks and followed up for an additional 4 weeks. The key safety end points were bleeding according to the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Thrombolysis in Myocardial Infarction (TIMI) classifications. Secondary objectives included platelet aggregation and major adverse cardiac events. Seven hundred and twenty subjects were randomized. Overall bleeding rates tended to be higher with atopaxar compared with placebo by CURE criteria (placebo, 0.6% atopaxar, 3.9% relative risk, 6.82, P =0.03 50 mg, 3.9% 100 mg, 1.7% 200 mg, 5.9% P for trend=0.01) and TIMI criteria (placebo, 6.8% atopaxar, 10.3% relative risk, 1.52, P =0.17 50 mg, 9.9% 100 mg, 8.1% 200 mg, 12.9% P for trend=0.07). There was no difference in major bleeding. Major adverse cardiac events were numerically lower in the atopaxar subjects. All atopaxar regimens achieved high levels of platelet inhibition. A transient elevation in liver transaminases and dose-dependent QTc prolongation without apparent complications were observed in higher-dose atopaxar treatment groups. In this dose-ranging study of patients with CAD, treatment with atopaxar resulted in platelet inhibition, more minor bleeding, and numerically but not statistically fewer ischemic events. Larger-scale trials are needed to determine whether these patterns translate into clinically meaningful effects. URL: www.ClinicalTrials.gov . Unique identifier: NCT00312052.
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.AHJ.2007.03.029
Abstract: Patients with metabolic syndrome are at increased risk for cardiovascular complications. We sought to determine whether peroxisome proliferator-activated receptor gamma agonists had any beneficial effect on patients with metabolic syndrome undergoing percutaneous coronary intervention (PCI). A total of 200 patients with metabolic syndrome undergoing PCI were randomized to rosiglitazone or placebo and followed for 1 year. Carotid intima-medial thickness (CIMT), inflammatory markers, lipid levels, brain natriuretic peptide, and clinical events were measured at baseline, 6 months, and 12 months. There was no significant difference in CIMT between the 2 groups. There was no difference in the 12-month composite end point of death, myocardial infarction (MI), stroke, or any recurrent ischemia (31.4% vs 30.2%, P = .99). The rate of death, MI, or stroke at 12 months was numerically lower in the rosiglitazone group (11.9% vs 6.4%, P = .19). There was a trend toward a greater decrease over time in high-sensitivity C-reactive protein values compared with baseline in the group randomized to rosiglitazone versus placebo both at 6 months (-35.4% vs -15.8%, P = .059) and 12 months (-40.0% vs -20.9%, P = .089) and higher change in high-density lipoprotein (+15.5% vs +4.1%, P = .05) and lower triglycerides (-13.9% vs +14.9%, P = .004) in the rosiglitazone arm. There was a trend toward less new onset diabetes in the rosiglitazone group (0% vs 3.3%, P = .081) and no episodes of symptomatic hypoglycemia. There was no excess of new onset of clinical heart failure in the rosiglitazone group, nor was there a significant change in brain natriuretic peptide levels. Patients with metabolic syndrome presenting for PCI are at increased risk for subsequent cardiovascular events. Rosiglitazone for 12 months did not appear to affect CIMT in this population, although it did have beneficial effects on high-sensitivity C-reactive protein, high-density lipoprotein, and triglycerides. Further study of peroxisome proliferator-activated receptor agonism in patients with metabolic syndrome undergoing PCI may be warranted.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JACC.2019.10.057
Abstract: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Baseline lipoprotein(a) levels (median: 21.2 mg/dl interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999 p = 0.0081). Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab NCT01663402).
Publisher: Elsevier BV
Date: 07-2021
Publisher: Massachusetts Medical Society
Date: 11-11-2010
Publisher: American Diabetes Association
Date: 15-03-2021
DOI: 10.2337/DC20-2842
Abstract: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02−1.06, P & 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85–1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment–baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03−1.12 P = 0.0002) for incident type 2 diabetes. In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.JACC.2018.03.008
Abstract: Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE. Among participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE, utations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months. We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. COMPASS was a randomized, double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular utation. A total of 128 patients experienced an incident of MALE. After MALE, the 1-year cumulative risk of a subsequent hospitalization was 61.5% for vascular utations, it was 20.5% for death, it was 8.3% and for MACE, it was 3.7%. The MALE index event significantly increased the risk of experiencing subsequent hospitalizations (hazard ratio [HR]: 7.21 p < 0.0001), subsequent utations (HR: 197.5 p < 0.0001), and death (HR: 3.23 p < 0.001). Compared with aspirin alone, the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43% (p = 0.01), total vascular utations by 58% (p = 0.01), peripheral vascular interventions by 24% (p = 0.03), and all peripheral vascular outcomes by 24% (p = 0.02). Among in iduals with lower extremity PAD, the development of MALE is associated with a poor prognosis, making prevention of this condition of utmost importance. The combination of rivaroxaban 2.5 mg twice daily and aspirin significantly lowered the incidence of MALE and the related complications, and this combination should be considered as an important therapy for patients with PAD. (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS] NCT01776424).
Publisher: Oxford University Press (OUP)
Date: 18-08-2015
Abstract: The aim was to describe outcomes among patients with stable coronary artery disease (CAD) with or without a history of myocardial revascularization in a large contemporary cohort. Patients with stable CAD were selected from the Reduction of Atherothrombosis for Continued Health (REACH) registry. The cohort was ided into patients with ( n = 25 583) and without ( n = 13 133) a history of myocardial revascularization. Crude outcomes were described according to the use and type of revascularization: percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The primary outcome was cardiovascular (CV) death. At baseline, the non-revascularized group was older and had more CV risk factors. At 36-month median follow-up, previous revascularization was associated with a lower risk of CV death [crude incidence rate (CIR): 6.82 vs. 9.08%, hazard ratio (HR) 0.73 [95% confidence interval (CI) 0.66-0.80] P < 0.01]. This association was seen for patients with a history of PCI (CIR 5.78 vs. 8.88%, HR 0.64 [0.58-0.71] P ≤ 0.01), but not with CABG (HR 1.26 [1.14-1.49] P < 0.01), and was consistent regardless of prior MI and the timing of prior revascularization. Among patients with stable CAD, a history of myocardial revascularization was associated with lower CV mortality, particularly when PCI was the mode of revascularization. Coronary artery disease patients managed non-invasively represent a high-risk group.
Publisher: Massachusetts Medical Society
Date: 04-10-2012
Publisher: Massachusetts Medical Society
Date: 04-08-2016
DOI: 10.1056/NEJMP1605260
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-06-2009
Publisher: Oxford University Press (OUP)
Date: 23-05-2019
Abstract: The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous Type 2, related to oxygen supply/demand imbalance Type 3, fatal without ascertainment of cardiac biomarkers Type 4, related to percutaneous coronary intervention and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95 P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99 P = 0.032) and Type 2 (0.77, 0.61–0.97 P = 0.025), but not Type 4 MI. After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.
Publisher: Springer Science and Business Media LLC
Date: 06-2012
DOI: 10.1007/S11239-012-0750-6
Abstract: Atopaxar is a reversible protease activated receptor (PAR)-1 thrombin receptor antagonist that interferes with platelet signaling. The effects of PAR-1 antagonists on biomarkers remain unknown. The primary objective was to assess the effects of atopaxar on biomarkers of inflammation and platelet activation. The LANCELOT-CAD trial randomized 720 subjects to atopaxar (50, 100, or 200 mg daily) or matching placebo for 24 weeks. Biomarkers were assessed at serial time points. A linear mixed model to account for repeated measures was used to evaluate the change in biomarker concentration from randomization across time to week 24. Least square means were determined from the linear mixed models. The concentration of sCD40L decreased on average over time by -553 (95 % CI -677, -429) ng/L in the combined atopaxar group versus -30.3 (-249 to 189) ng/L fall in the placebo arm (P < 0.001) and a dose-dependent trend was seen across treatment groups (P < 0.001 for trend). In contrast, Lp-PLA(2) mass rose on average over time by 12.6 (95 % CI 10.0, 15.3) ng/ml in the combined atopaxar group as compared with 2.6 (95 % CI -2.1, 7.3) ng/ml in the placebo arm (P < 0.001). Similarly, the concentration of IL-18 rose by 17.5 (95 % CI 12.4, 22.6) pg/ml in the atopaxar group versus a -1.2 (95 % CI -10.2, 7.8) pg/ml fall in the placebo group (P < 0.001). The effects of atopaxar on Lp-PLA(2) and IL-18 appeared to be dose-dependent (P < 0.001 for trend) and were observed in J-LANCELOT. Atopaxar did not have a significant effect on other inflammatory markers. In conclusion, atopaxar appeared to decrease sCD40L, but did not demonstrate an anti-inflammatory effect in patients with stable CAD. Although atopaxar increased the concentration of Lp-PLA(2) and IL-18, the clinical relevance of these findings remains unknown and warrants further investigation and validation.
Publisher: MDPI AG
Date: 14-09-2018
Abstract: Chronic hepatitis C (HCV) is a public health priority in the European Union/European Economic Area (EU/EEA) and is a leading cause of chronic liver disease and liver cancer. Migrants account for a disproportionate number of HCV cases in the EU/EEA (mean 14% of cases and % of cases in some countries). We conducted two systematic reviews (SR) to estimate the effectiveness and cost-effectiveness of HCV screening for migrants living in the EU/EEA. We found that screening tests for HCV are highly sensitive and specific. Clinical trials report direct acting antiviral (DAA) therapies are well-tolerated in a wide range of populations and cure almost all cases ( %) and lead to an 85% lower risk of developing hepatocellular carcinoma and an 80% lower risk of all-cause mortality. At 2015 costs, DAA based regimens were only moderately cost-effective and as a result less than 30% of people with HCV had been screened and less 5% of all HCV cases had been treated in the EU/EEA in 2015. Migrants face additional barriers in linkage to care and treatment due to several patient, practitioner, and health system barriers. Although decreasing HCV costs have made treatment more accessible in the EU/EEA, HCV elimination will only be possible in the region if health systems include and treat migrants for HCV.
Publisher: Massachusetts Medical Society
Date: 10-12-2009
Publisher: Oxford University Press (OUP)
Date: 09-12-2008
Abstract: We aimed to determine the relationship between body mass index (BMI) and cardiovascular events among in iduals with or at-risk of atherothrombotic disease. This was a prospective observational study of 15 532 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial who were randomly assigned to clopidogrel or placebo, and followed-up for a median of 28 months for the occurrence of the primary endpoint (cardiovascular death, myocardial infarction, or stroke), all-cause mortality, and bleeding complications. Compared with the highest BMI quartile, the primary endpoint, cardiovascular, and all-cause mortality all occurred more frequently among patients in the lowest BMI quartile (about a third lower). The relationship between continuous BMI and adverse cardiovascular outcomes were presented as two linear spline terms with 29 kg/m(2) as the cut-point for all-cause mortality. Lower BMI was associated with an increase in moderate and severe bleeding complications, largely accounted for by those receiving dual-antiplatelet agents with the highest tertile aspirin dose. Adverse cardiovascular events and bleeding complications occurred more frequently among in iduals with or at-risk for atherothrombotic disease and low BMI. Further studies should be directed to these patients to improve outcomes.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Wiley
Date: 04-08-2009
DOI: 10.1111/J.1755-5922.2009.00090.X
Abstract: Australia's Pharmaceutical Benefits Scheme supports the use of effective drugs for the prevention and control of cardiovascular risk factors. However, there are little data available describing per person costs of medication in primary prevention and secondary prevention in the community. We aim to understand annual expenditure on cardiovascular medicines according to the level and extent of cardiovascular disease, using participants enrolled in the Reduction of Atherothrombosis for Continued Health (REACH) registry. 2873 participants were recruited into the REACH registry through 273 Australian general practices. Cardiovascular medicines review was undertaken at baseline. Average weighted costs of medications were estimated using government-reimbursed prices. Annual costs were stratified by disease extent and location. The annual mean cost of pharmaceuticals per person was 1307 AU dollars. The average reported medicine use per person across all states and participants groups varied significantly. Participants with cerebrovascular or peripheral arterial disease were prescribed less cardiovascular medication than those with coronary artery disease (CAD) (mean number of drugs 3.5 vs. 4.5, P < 0.0001) and (3.6 vs. 4.5, P < 0.0001), while those with risk factor alone had the same medication use as those with CAD (mean number 4.5). Medication use was lower in Western Australia in comparison to eastern States. Participants with existing cerebrovascular disease and peripheral vascular disease receive less preventive therapy than those with CAD or even risk factors alone. This observation is consistent across all mainland states. Given the evidence of the effectiveness and cost-effectiveness of treating all types of vascular diseases, the present study suggests that there is scope to improve the treatment of these high-risk participants in Australia.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Massachusetts Medical Society
Date: 15-02-2018
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.CLINTHERA.2010.01.009
Abstract: The management of atherothrombotic disease is responsible for a large proportion of direct medical costs in most countries, imposing a substantial financial burden on health care payers. There is limited knowledge about direct per-person medical costs using a "bottom-up" approach. This study was designed to estimate the per-person direct medical costs incurred by communitybased subjects in Australia who have or are at high risk for atherothrombotic disease. The perspective was a governmental one, at the federal level for pharmaceuticals and at the state level for hospitalizations. One-year follow-up data were obtained for Australian participants in the international REACH (Reduction of Atherothrombosis for Continued Health) Registry who were aged >or=45 years and had either established atherothrombotic disease (coronary artery disease, cerebrovascular disease, or peripheral artery disease [PAD]) or >or=3 risk factors for atherothrombotic disease. Information was extracted on the use of cardiovascular medications, hospitalizations, general practice visits, clinical pathology and imaging studies, and use of rehabilitation services. Bottom-up costing was undertaken by assigning unit costs to each health care item, based on Australian government reimbursement data for 2006-2007. Costs were estimated in Australian dollars. Data for 2873 Australian participants in the REACH Registry were included in the analysis. Mean (SD) annual pharmaceutical costs per person were A$1388 (A$645). Mean ambulatory care costs per person were A$704 (A$492), and mean hospitalization costs were A$10,711 (A$10,494). Compared with participants with >or=3 risk factors (adjusted for age and sex), participants with 2 to 3 affected vascular territories incurred A$160 more in mean pharmaceutical costs (95% CI, 78 to 256) and A$181 more in ambulatory care costs (95% CI, 107 to 252). Mean ambulatory care costs were A$132 greater among participants with PAD only relative to those with >or=3 risk factors (95% CI, 19 to 272). Hospital costs were not significantly increased with an increasing number of affected vascular territories. The greatest difference in direct hospital costs (A$943) was between participants with PAD relative to those with >or=3 risk factors (95% CI, -564 to 3545). From the government perspective, management of atherothrombotic disease in Australia was costly during the period studied, particularly among those with PAD only or disease affecting 2 to 3 vascular territories. Hospitalization accounted for the majority of health care expenditure associated with atherothrombotic disease, although the number of hospitalized participants was relatively small.
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Location: United States of America
No related grants have been discovered for Deepak Bhatt.