ORCID Profile
0000-0003-4050-5030
Current Organisation
University of Queensland School of Medicine
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Publisher: Springer Science and Business Media LLC
Date: 03-2000
DOI: 10.2165/00002512-200016030-00003
Abstract: With increasing age of the general population, cardiovascular diseases are becoming a greater health burden. Coronary artery disease remains a major cause of morbidity and mortality worldwide. Among the various pathophysiological processes, platelets play a pre-eminent role. With the identification of the glycoprotein (GP) IIb/IIIa receptor as the final common pathway for platelet aggregation, potent antiplatelet agents have been developed. These GP IIb/IIIa antagonists have been shown to be effective in improving outcomes among patients undergoing percutaneous coronary interventions and for the treatment of acute coronary syndromes. By pooling the results of several large-scale trials, these benefits have been found to extend to the elderly population. Among 7860 patients undergoing percutaneous coronary intervention, the occurrence of death or myocardial infarction at 30 days was reduced from 10.0 to 5.9% (odds ratio 0.56 95% confidence level, 0.37 to 0.83) with abciximab compared with placebo, in those >70 years of age. Importantly, this benefit was achieved without an increase in major bleeding complications. Similarly favourable trends were also observed among elderly patients treated with tirofiban or eptifibatide for acute coronary syndromes. As such, GP IIb/IIIa antagonists are effective in preventing ischaemic complications and can be safely administered to elderly patients.
Publisher: Elsevier BV
Date: 08-2005
DOI: 10.1016/J.AMJCARD.2005.04.005
Abstract: Thrombocytopenia that develops after percutaneous coronary intervention (PCI) may result in hemorrhagic complications, requirement for blood product transfusions, and potentially thrombotic or ischemic complications. The incidence and prognostic significance of thrombocytopenia, in patients with acute myocardial infarction (AMI) who undergo primary PCI have not been evaluated. In the CADILLAC trial 2,082 patients who had AMI within 12 hours of onset without shock were prospectively randomized to receive balloon angioplasty with or without abciximab versus stenting with or without abciximab. Acquired thrombocytopenia, defined as a nadir platelet count <100 x 10(9)/L in patients who did not have baseline thrombocytopenia, developed in 50 of 1,975 qualifying patients (2.5%) after primary PCI. By multivariate analysis, acquired thrombocytopenia developed more frequently in patients who had non-insulin-requiring diabetes mellitus (odds ratio 3.88 [OR], p = 0.0002), previous statin administration (OR 3.28, p = 0.002), and use of abciximab (OR 2.06, p = 0.02) and less frequently in patients who had previous aspirin use (OR 0.26, p = 0.002), a higher baseline platelet count (OR 1.20, p < 0.0001), and greater body mass index (OR 0.90, p = 0.006). Patients who developed thrombocytopenia versus those who did not had higher in-hospital rates of major hemorrhagic complications (10.0% vs 2.7%, p = 0.01), greater requirement for blood transfusions (10.0% vs 3.9%, p = 0.05), longer hospital stay (median 4.8 vs 3.6 days, p = 0.008), and increased costs (median dollar 14,466 vs dollar 11,629, p = 0.001). All-cause mortality was markedly increased at 30 days (8.0% vs 1.6%, p = 0.0008) and at 1 year (10.0% vs 3.9%, p = 0.03) in patients who developed thrombocytopenia. In conclusion, thrombocytopenia that develops after primary PCI for AMI, although uncommon, is associated with increased hemorrhagic complications and decreased survival.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-10-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-02-2016
DOI: 10.1161/CIRCULATIONAHA.115.017001
Abstract: Previous studies examining early readmission after acute myocardial infarction have focused exclusively on inpatient readmissions. However, from a patient’s perspective, any unplanned inpatient or observation rehospitalization after acute myocardial infarction represents a significant event these unplanned rehospitalizations have not been well characterized. We examined all patients with acute myocardial infarction treated with percutaneous coronary intervention and discharged alive from 233 hospitals in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Our primary outcome was unplanned rehospitalizations (inpatient or observation status) within 30 days after discharge. We identified factors associated with unplanned rehospitalizations using multivariable logistic regression. Among 12 312 patients, 1326 (10.8%) had 1483 unplanned rehospitalizations within 30 days of the index event: 1028 (69.3%) were inpatient readmissions, and 455 (30.7%) were observation stays. The majority of unplanned rehospitalizations (72%) were for cardiovascular reasons. Variation in hospital rates of 30-day unplanned rehospitalization ranged from 5.4% to 20.0%, with a median of 10.7%. After multivariable modeling, the factors most strongly associated with unplanned rehospitalization were baseline quality of life and depression, followed by index hospital length of stay. Early unplanned rehospitalizations are common after acute myocardial infarction, and close to one third were classified as an observation stay. Predischarge and postdischarge assessments of overall, not just cardiovascular, health and strategies to optimize patient functional status may help to reduce unplanned rehospitalizations. URL: www.clinicaltrials.gov . Unique identifier: NCT01088503.
Publisher: Elsevier BV
Date: 2016
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.JCIN.2009.07.009
Abstract: The aim of this report was to evaluate 12-month outcomes of facilitated percutaneous coronary intervention (PCI) in the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) trial. Treatment delays remain common for patients with primary PCI leading to studies evaluating possible benefit of "facilitated" PCI. In the FINESSE trial, no reduction in the 90-day primary ischemic end point and an increase in bleeding were observed with both facilitated approaches, although modest favorable trends were seen for some patient subgroups. A total of 2,452 patients with ST-segment elevation myocardial infarction (MI) and anticipated 1 to 4 h delay until catheterization were randomized to reduced-dose reteplase + abciximab, abciximab alone, or placebo, followed by expedited primary PCI. Placebo-treated patients received abciximab in the cath lab. One-year mortality was a pre-specified secondary end point. One-year mortalities in the 3 groups noted in the preceding text were 6.3%, 7.4%, and 7.0%, respectively (p = NS), representing 1.1%, 1.9%, and 2.5% increments since the 90-day outcome (p = 0.053 for combination treatment vs. primary PCI). A favorable trend with combination treatment was seen for patients with anterior MI (p = 0.09), but no other specified groups benefited or tended to benefit. Independent baseline correlates of 1-year mortality were systolic blood pressure 1, anterior MI, body mass index 100 beats/min, and no statin use. These results suggest that widespread utilization of the facilitated approaches tested cannot be justified, but that high-risk patient groups such as patients with anterior MI may deserve further study. (The FINESSE trial NCT00046228).
Publisher: Wiley
Date: 08-10-2017
DOI: 10.1002/CCD.27145
Abstract: To understand the optimal timing of adenosine diphosphate (ADP) receptor inhibitor pretreatment prior to percutaneous coronary intervention (PCI) among acute myocardial infarction (MI) patients. The role of ADP receptor inhibitor pretreatment in this population is unclear. A total of 9,251 ADP receptor inhibitor-naïve MI patients undergoing PCI at 229 TRANSLATE-ACS sites were evaluated. Adjusted risks of in-hospital major adverse cardiovascular events (MACE) and major bleeding were compared among patients with and without pretreatment using inverse probability-weighted propensity adjustment. Of 9,251 patients treated with either prasugrel or clopidogrel during the index MI hospitalization, 4,056 (44%) received pretreatment (ST-segment elevation MI [STEMI] 54.9%, non-STEMI 45.1%) pretreatment was used more commonly among those receiving clopidogrel than prasugrel (52% vs. 20%, P < 0.0001). MACE risks were not significantly different between patients with and without pretreatment (clopidogrel 2.1% vs. 2.2%, adjusted hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.70-1.43 prasugrel 2.1% vs. 2.3%, adjusted odds ratio [OR] 0.82, 95% CI 0.42-1.60). No differences in major bleeding were observed among those receiving versus not receiving pretreatment (clopidogrel 3.1% vs. 3.5%, adjusted HR 0.94, 95% CI 0.65-1.36 prasugrel 2.5% vs. 2.7%, adjusted OR 0.93, 95% CI 0.42-2.02) results were similar when stratified by MI type. ADP receptor inhibitor pretreatment (44%) is commonly used among acute MI patients undergoing PCI in contemporary practice, but no significant differences were found in in-hospital MACE and/or bleeding risks between patients receiving versus not receiving pretreatment, regardless of ADP receptor inhibitor type.
Publisher: Wiley
Date: 23-10-2018
DOI: 10.1002/CCD.27860
Abstract: To investigate the prevalence, predictors and associations between guideline-directed medical therapy (GDMT) and clinical outcomes in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) from eight academic centers in the United States. Evidence for GDMT in patients with AMI comes from randomized controlled trials. The use of GDMT in clinical practice is unknown in this setting. PROMETHEUS is a multicenter observational registry comprising 19,914 patients with acute coronary syndrome (ACS) undergoing PCI. Patients with AMI were ided into two groups based on the prescription of GDMT or not (non-GDMT) at discharge. GDMT was defined according to American College of Cardiology/American Heart Association (ACC/AHA) class I recommendations, specifically, dual antiplatelet therapy, statin and beta-blocker for all AMI patients, and additional ACEI/ARB in patients with left ventricular ejection fraction (LVEF) less than 40%, hypertension, diabetes mellitus (DM) or chronic kidney disease (CKD). The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause death, MI, stroke or unplanned target vessel revascularization (TVR) at 1 year. Out of 4,834 patients with AMI, 3,356 (69.4%) patients were discharged on GDMT. Patients receiving GDMT were more often younger and male. Compared with non-GDMT patients, GDMT patients had a significantly lower frequency of comorbidities. Predictors of greater GDMT prescription at discharge were ST-segment elevation myocardial infarction (STEMI), and increased body mass index (BMI), whereas hypertension, prior PCI, anemia and CKD were associated with less GDMT prescription. At 1 year, the use of GDMT was associated with a significantly lower incidence of MACE (13.7% vs. 22.5% adjusted HR 0.68 95%CI 0.58-0.80 P < 0.001), death (3.7% vs. 9.4% adjusted HR 0.61 95%CI 0.46-0.80 P < 0.001), and unplanned TVR (8.4% vs. 11.3% adjusted HR 0.76 95%CI 0.61-0.96 P = 0.020). However, there were no significant differences in the incidence of MI (4.3% vs. 7.0% adjusted HR 0.75 95%CI 0.56-1.01 P = 0.056), stroke (1.5% vs. 2.0% adjusted HR 0.79 95%CI 0.47-1.34 P = 0.384) between the two groups. In a contemporary practice setting in the United States, GDMT was utilized in just over two-thirds of AMI patients undergoing PCI. Predictors of GDMT prescription at discharge included STEMI, BMI and absence of hypertension, CKD, anemia or prior PCI. Use of GDMT was associated with significantly lower risk of 1-year MACE and mortality.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-01-2016
Abstract: Longitudinal clinical investigations often rely on patient reports to screen for postdischarge adverse outcomes events, yet few studies have examined the accuracy of such patient reports. Patients with acute myocardial infarction ( MI ) in the TRANSLATE ‐ ACS study were asked during structured interviews at 6 weeks, 6 months, and 12 months postdischarge to report any rehospitalizations. The accuracy of patient‐reported rehospitalizations within 1 year of postdischarge was determined using claims‐based medical bill validation as the reference standard. The cumulative incidence of rehospitalizations was compared when identified by patient report versus medical bills. Patients were categorized by the accuracy in reporting events (accurate, under‐, or over‐ reporters) and characteristics were compared between groups. Among 10 643 MI patients, 4565 (43%) reported 7734 rehospitalizations. The sensitivity and positive predictive value of patient‐reported rehospitalizations were low at 67% and 59%, respectively. A higher cumulative incidence of rehospitalization was observed when identified by patient report versus medical bills (43% vs 37% P .001). Overall, 18% of patients over‐reported and 10% under‐reported the number of hospitalizations. Compared with accurate reporters, under‐reporters were more likely to be older, female, African American, unemployed, or a non‐high‐school graduate, and had greater prevalence of clinical comorbidities such as diabetes and past cardiovascular disease. The accuracy of patient‐reported rehospitalizations was low with patients both under‐ and over‐reporting events. Longitudinal clinical research studies need additional mechanisms beyond patient report to accurately identify rehospitalization events. URL : clinicaltrials.gov . Unique identifier: NCT 01088503.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2008
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.JACC.2010.02.072
Abstract: The objective was to evaluate the pharmacodynamic response of switching patients on maintenance phase clopidogrel therapy after an acute coronary syndrome (ACS) to prasugrel. Prasugrel P2Y(12) receptor blockade is associated with greater pharmacodynamic platelet inhibition and reduction of ischemic complications compared with that of clopidogrel in ACS patients undergoing percutaneous coronary intervention. The pharmacodynamic effects of switching patients during maintenance phase clopidogrel therapy after an ACS event to prasugrel are unknown. The SWAP (SWitching Anti Platelet) study was a phase 2, multicenter, randomized, double-blind, double-dummy, active-control trial. After a run-in of daily open-label clopidogrel 75 mg with aspirin therapy for 10 to 14 days, patients were randomly assigned to 1 of the following 3 treatments: placebo loading dose (LD)/clopidogrel 75 mg maintenance dose (MD), placebo LD rasugrel 10 mg MD, or prasugrel 60 mg LD/10 mg MD. Platelet function was evaluated at 2 h, 24 h, 7 days, and 14 days using light transmittance aggregometry, VerifyNow P2Y(12) assay, and vasodilator-stimulated phosphoprotein phosphorylation. A total of 139 patients were randomized, of whom 100 were eligible for analysis. Maximum adenosine diphosphate-induced platelet aggregation (20 μM) by light transmittance aggregometry at 1 week (primary end point) was lower after prasugrel MD compared with clopidogrel MD (41.1% vs. 55.0%, p < 0.0001), and was also lower in the prasugrel LD+MD group compared with clopidogrel MD (41.0% vs. 55.0%, p < 0.0001). At 2 h, a prasugrel LD resulted in higher platelet inhibition compared with the other regimens. Similar results were found using light transmittance aggregometry with 5 μM adenosine diphosphate, VerifyNow P2Y(12), and vasodilator-stimulated phosphoprotein phosphorylation assays. For patients receiving maintenance clopidogrel therapy after an ACS event, switching from clopidogrel to prasugrel is associated with a further reduction in platelet function by 1 week using prasugrel MD or within 2 h with the administration of a prasugrel LD. (A Pharmacodynamic Comparison of Prasugrel [LY640315] Versus Clopidogrel in Subjects With Acute Coronary Syndrome Who Are Receiving Clopidogrel [SWAP] NCT00356135).
Publisher: Wiley
Date: 17-01-2019
DOI: 10.1002/CCD.28033
Abstract: To investigate the use of prasugrel after percutaneous coronary intervention (PCI) in African American (AA) patients presenting with acute coronary syndrome (ACS). AA patients are at higher risk for adverse cardiovascular outcomes after PCI and may derive greater benefit from the use of potent antiplatelet therapy. Using the multicenter PROMETHEUS observational registry of ACS patients treated with PCI, we grouped patients by self-reported AA or other races. Clinical outcomes at 90-day and 1-year included non-fatal myocardial infarction (MI), major adverse cardiac events (composite of death, MI, stroke, or unplanned revascularization) and major bleeding. The study population included 2,125 (11%) AA and 17,707 (89%) non-AA patients. AA patients were younger, more often female (46% vs. 30%) with a higher prevalence of diabetes mellitus, chronic kidney disease, and prior coronary intervention than non-AA patients. Although AA patients more often presented with troponin (+) ACS, prasugrel use was much less common in AA vs. non-AA (11.9% vs. 21.4%, respectively, P = 0.001). In addition, the use of prasugrel increased with the severity of presentation in non-AA but not in AA patients. Multivariable logistic regression showed AA race was an independent predictor of reduced use of prasugrel (0.42 [0.37-0.49], P < 0.0001). AA race was independently associated with a significantly higher risk of MI at 90-days and 1 year after PCI. Despite higher risk clinical presentation and worse 1-year ischemic outcomes, AA race was an independent predictor of lower prasugrel prescription in a contemporary population of ACS patients undergoing PCI.
Publisher: Informa Healthcare
Date: 10-07-2015
DOI: 10.3111/13696998.2015.1060979
Abstract: To compare healthcare resource utilization (HCRU) and healthcare costs in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with prasugrel or ticagrelor. Hospital charge master data were used to identify ACS-PCI patients aged ≥ 18 years with ≥ 1 in-hospital claim for prasugrel or ticagrelor between August 1, 2011-April 30, 2013. Treatment groups were propensity matched for baseline and index hospitalization characteristics. HCRU and costs were assessed through 90-days post-discharge. Costs were determined based on hospital-specific cost-to-charge ratios and adjusted to 2013 US dollars. Before matching, ticagrelor patients were older, more-often female, and had increased cardiovascular (CV) and bleeding risks compared with prasugrel patients. Propensity-matched length of index hospital stay (4.7 vs 4.9 days, p = 0.23) and risk for all-cause [30-day: relative risk (RR) = 0.86 95% CI = 0.73-1.0 90-day: RR = 0.90 95% CI = 0.80-1.0, and CV-related (30-day: RR = 0.77 95% CI = 0.59-1.0 90-day: RR = 0.89 95% CI = 0.73-1.1) re-hospitalizations did not significantly differ between prasugrel and ticagrelor, respectively. Compared to ticagrelor, the propensity-matched risk of re-hospitalization for myocardial infarction (MI) (30-day: RR = 0.39 95% CI = 0.21-0.75 90-day: RR = 0.53 95% CI = 0.34-0.81) and an outpatient medical encounter for dyspnea (30-day: RR = 0.49 95% CI = 0.33-0.74 90-day: RR = 0.60 95% CI = 0.46-0.80) were significantly lower for prasugrel patients, with no significant differences in bleeding encounters between groups (30-day: RR = 0.87 95% CI = 0.54-1.40 90-day: RR = 1.0 95% CI = 0.71-1.50). Matched total healthcare costs were not significantly different between groups during the index hospitalization ($36,011 vs $37,247, p = 0.21), 30-days post-discharge ($2007 vs $2522, p = 0.48), 90-days post-discharge ($4564 vs $5242, p = 0.49), and aggregate of the index hospitalization through 90-day follow-up ($40,576 vs $42,494, p = 0.09) timeframes. Re-hospitalization for MI and outpatient encounters for dyspnea were lower in prasugrel treated than in ticagrelor treated ACS-PCI patients up to 90-days post-index hospitalization discharge, with no difference in bleeding encounters or healthcare costs between the two populations. This data supports the utility of prasugrel in routine clinical practice. These findings should be considered within limitations of observational research.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-07-2023
Abstract: Internet‐based participation has the potential to enhance pragmatic and decentralized trials, where representative study populations and generalizability to clinical practice are key. We aimed to study the differences between internet and noninternet/telephone participants in a large remote, pragmatic trial. In a subanalysis of the ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) study, we compared internet participants with those who opted for noninternet participation. Study process measures examined included participant characteristics at consent, study medication adherence, and study retention. The clinical outcome examined was a composite of all‐cause mortality, hospitalization for myocardial infarction, or hospitalization for stroke. Noninternet participants were older (mean 69.4 versus 67.4 years), more likely to be female (38.9% versus 30.2%), more likely to be Black (27.3% versus 6.0%) or Hispanic (11.1% versus 2.0%), and had a higher number of comorbid conditions. The composite clinical outcome was more than twice as high in noninternet participants. The hazard of nonadherence to the assigned aspirin dosage was 46% higher in noninternet participants than internet participants. Noninternet participants differed from internet participants in notable demographic characteristics while having poorer baseline health. Over the course of ADAPTABLE, they also had worse clinical outcomes and greater likelihood of study drug nonadherence. These results suggest that trials focused on internet participation select for younger, healthier participants with a higher proportion of traditionally overrepresented patients. Allowing noninternet participation enhances ersity however, additional steps may be needed to promote study retention and study medication adherence. clinicaltrials.gov . Identifier: NCT02697916.
Publisher: Oxford University Press (OUP)
Date: 15-03-2016
DOI: 10.2146/AJHP150065
Abstract: Results of a study of bleeding events and other inhospital outcomes with the use of clopidogrel versus prasugrel in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) are reported. Demographic and clinical data on adults hospitalized for ACS, managed with PCI, and treated with clopidogrel or prasugrel during a two-year period were extracted from a large hospital claims database. Bleeding rates, hospital length of stay (LOS), and total hospital costs during the index hospitalization were evaluated. The study s le consisted of 75,297 patients who received clopidogrel and 9,477 who received prasugrel. The unadjusted bleeding rates were 5.7% with clopidogrel use and 3.2% with prasugrel use (p < 0.0001). After propensity score stratification to adjust for selection bias, rates of bleeding events were not significantly different between clopidogrel- and prasugrel-treated patients (odds ratio, 0.90 95% confidence interval [CI], 0.80-1.02 p = 0.0949). The adjusted mean ± S.D. hospital LOS was 0.22 day lower (95% CI, 0.15-0.28 p < 0.001) with the use of prasugrel versus clopidogrel, and adjusted total mean hospital costs were $375 less for prasugrel-treated patients (p = 0.003). After adjustments for demographic and clinical characteristics, rates of inhospital bleeding in patients who received prasugrel and those who received clopidogrel were not significantly different. The adjusted analyses showed that the mean hospital LOS was shorter and total mean hospital costs were lower for patients treated with prasugrel.
Publisher: Georg Thieme Verlag KG
Date: 2013
DOI: 10.1160/TH12-06-0378
Abstract: The prevalence of high platelet reactivity (HPR) in patients who have switched from clopidogrel to prasugrel during maintenance phase after an acute coronary syndrome (ACS) event is unknown. Therefore, the effect of switching from clopidogrel to prasugrel on the prevalence of HPR was evaluated. This analysis from the previously reported SWAP (SWitching Anti Platelet) study assessed HPR at baseline, 2 and 24 hours, and seven days after switching from clopidogrel to prasugrel maintenance dose (MD), with or without a prasugrel loading dose (LD) using four definitions: maximum platelet aggregation (MPA) % (primary endpoint), MPA %, P2Y12 reaction units (PRU) , and platelet reactivity index (PRI) ≥50%. A total of 95 patients were available for analysis 56 patients provided DNA for genetic assessments of cytochrome P450 (CYP) 2C19. There were 26 (27.4%) patients with HPR at the end of the clopidogrel run-in (defined as MPA %). The HPR prevalence varied by each definition and ranged from 19% (PRU ) to 68% (PRI ≥50%). A significantly higher HPR prevalence was observed during clopidogrel versus the combined prasugrel therapy groups at seven days as measured by MPA % (21.2% vs. 4.5%, p .05), PRU (18.8% vs. 0%, p=0.001), and PRI ≥50% (66.7% vs. 7.9%, p .0001). There was a significantly higher percentage of subjects carrying at least one reduced function allele with HPR measured by MPA % (p=0.02) or PRU (p=0.05) than non-carriers with HPR. Switching ACS patients during maintenance clopidogrel therapy to prasugrel with or without an LD is associated with a reduced HPR prevalence and may provide an alternative strategy to treat patients with HPR, independent of CYP2C19 genotype.
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.JCIN.2009.06.018
Abstract: We hypothesized that patients most likely to benefit would be those at high risk with a shorter duration of acute ischemia and who required transfer for percutaneous coronary intervention (PCI). The FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) study failed to demonstrate an improvement in the 90-day composite clinical end point of early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or abciximab alone. We performed a retrospective analysis of 2,452 patients in this double-blind, placebo-controlled study. Patients were stratified by Thrombolysis In Myocardial Infarction (TIMI) risk score for ST-segment elevation myocardial infarction (STEMI), presentation to a spoke (no PCI available) or hub site, and symptom-to-randomization time. Outcomes included the primary composite end point of death, ventricular fibrillation after 48 h, cardiogenic shock, and congestive heart failure through day 90 as well as 1-year mortality. Mortality for all patients at 1 year was directly related to TIMI risk score (23 of 1,223 = 1.9% in patients with score or =3, p or =3 and presentation to a spoke site with a symptom-to-randomization time or =3 and spoke site alone (HR: 0.549, p = 0.06). Facilitation of PCI with a combination of abciximab and half-dose reteplase improved survival at 1 year in high-risk patients presenting to a spoke hospital with symptom-to-randomization time < or =4 h. Further prospective study of facilitated PCI in this subgroup of patients is warranted.
Publisher: Elsevier BV
Date: 10-2009
Publisher: Elsevier BV
Date: 08-2000
DOI: 10.1016/S0003-4975(00)01343-6
Abstract: Abciximab during percutaneous coronary revascularization reduces ischemic complications, but concern exists regarding increased bleeding risk should emergency coronary surgical procedures be required. Outcomes were assessed among 85 patients who required coronary artery bypass grafting operations after coronary intervention in two randomized placebo-controlled trials of abciximab. Comparisons were made between patients in the pooled placebo and abciximab groups. The incidence of coronary surgical procedures was 2.17% and 1.28% among patients randomized to placebo and abciximab, respectively (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients in the placebo and abciximab groups, respectively (p = 0.059). Rates of major blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p = 0.27) transfusions of packed red blood cells or whole blood were administered in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for bleeding was required in 3% and 12% of patients, respectively. Death and myocardial infarction tended to occur less frequently among patients who had received abciximab. Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.
Publisher: Elsevier BV
Date: 07-1999
DOI: 10.1053/HJ.1999.V138.99236
Abstract: Even with continued improvements in the technology of percutaneous coronary intervention (PCI), approximately 10% to 20% of patients undergoing PCI will require repeat procedures within 1 year. Furthermore, because of the chronic nature of coronary artery disease, many patients will require additional treatment with PCI well after an initial episode of care. Abciximab (ReoPro), a chimeric (murine/human) monoclonal antibody fragment (c7E3 Fab), has been shown to significantly improve periprocedural and long-term outcomes associated with PCI and to reduce the need for repeat target vessel revascularization. However, because the structure of abciximab is derived from an antibody, concern has been raised about subsequent repeat administration. To prospectively evaluate the safety and efficacy of abciximab readministration, we established the ReoPro Readministration Registry with the intent to determine the efficacy, human antichimeric antibody response and rates of thrombocytopenia, bleeding, intracranial hemorrhage, and anaphylaxis in at least 500 patients being retreated with abciximab. The study was conducted at 19 centers beginning in March 1997. This article details interim data that are based on the first 329 patients. Data to date indicate that readministration with abciximab is safe and efficacious and that the same indications for first-time use should apply to subsequent readministration.
Publisher: Elsevier BV
Date: 03-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-09-2003
DOI: 10.1161/01.CIR.0000087601.45803.86
Abstract: Background— Trials of platelet glycoprotein IIb/IIIa inhibitors as adjuncts to primary percutaneous coronary intervention for acute myocardial infarction (MI) have shown improved early clinical and angiographic outcomes with treatment. However, variations in trial designs, modest s le sizes, and limited long-term follow-up have precluded these studies from being definitive. Methods and Results— As a prespecified secondary analysis of the CADILLAC trial, we compared early and late outcomes by abciximab assignment among 2082 patients randomized in an open-label, 2×2 factorial-design trial of primary stenting versus angioplasty and abciximab treatment (n=1052) versus no abciximab treatment (n=1030). Baseline characteristics were balanced between groups. Abciximab treatment was associated with a significant reduction in the composite end point of death, MI, ischemia-driven target-vessel revascularization (TVR), or disabling stroke at 30 days (4.6% versus 7.0% relative risk, 0.65 95% CI, 0.46 to 0.93 P =0.01). Subacute thrombosis also was significantly reduced with abciximab treatment. At 12 months, however, rates of the composite end point did not differ significantly (18.4% for controls versus 16.9% for abciximab-treated patients relative risk, 0.92 95% CI, 0.76 to 1.10 P =0.29), reflecting a decrease in the relative difference in TVR rates (ie, no effect of abciximab on reducing restenosis). In an angiographic substudy (n=656), myocardial salvage, restenosis, and infarct-artery reocclusion at 7 months were unaffected by abciximab treatment. There was no significant interaction between stenting and abciximab treatment. Conclusions— Adjunctive abciximab treatment during primary percutaneous coronary intervention significantly enhanced 30-day event-free survival, predominantly by reducing ischemia-driven TVR. Abciximab treatment did not affect the composite end point at 1 year, reflecting a lack of effect on restenosis.
Publisher: Elsevier BV
Date: 02-1998
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-10-2009
Publisher: Wiley
Date: 14-06-2019
DOI: 10.1002/CCD.28369
Abstract: Stroke represents a potentially calamitous complication among patients with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). Data on the distribution of stroke occurrence post-PCI and its impact on mortality are scarce. We sought to determine the incidence, predictors and impact of stroke on mortality in ACS patients undergoing PCI. A total of 19,914 ACS patients underwent PCI in the PROMETHEUS multicenter observational study. We calculated the cumulative stroke incidence at 30 days and 1 year using the Kaplan Meier method. We also compared the distribution of stroke, myocardial infarction (MI), and bleeding across time and evaluated their overlap. Predictors of stroke were identified through multivariable Cox-regression. Stroke, MI, and bleeding were assessed as time-updated covariates to estimate how each impacts subsequent mortality. We found that 244 patients had a stroke within 1 year, a cumulative incidence of 1.5%. Previous cerebrovascular disease was the strongest predictor for post-PCI stroke, followed by ST-elevation MI presentation, hypertension, non-ST-elevation MI presentation, smoking, female sex, and age. Mortality risk was significantly higher among those who had a stroke versus those who did not (adjusted HR 4.84, p < .0001). However, the association attenuated over time with a much larger effect in the first 30 days of its occurrence (adjusted HR 17.7 95% CI: 12.3-25.4, p < .0001) versus beyond 30 days (adjusted HR 1.22 95% CI: 0.6-2.46, p = .58). Stroke occurrence within 1 year was not uncommon for ACS patients undergoing PCI. When compared with MI and bleeding, stroke had a substantial impact on mortality that attenuated rapidly over time.
Publisher: Georg Thieme Verlag KG
Date: 2013
DOI: 10.1160/TH13-03-0263
Abstract: Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers extensive metabolisers [EM] = *1/1 homozygotes reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.
Publisher: Elsevier BV
Date: 10-2009
Publisher: Georg Thieme Verlag KG
Date: 2014
DOI: 10.1160/TH13-09-0747
Abstract: High on-treatment platelet reactivity (HPR) has been identified as an independent risk factor for ischaemic events. The randomised, doubleblind, TRIPLET trial included a pre-defined comparison of HPR in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) following a placebo/600-mg clopidogrel loading dose (LD) immediately before a subsequent prasugrel 60-mg or 30-mg LD. Platelet reactivity was assessed using the VerifyNow® P2Y12 assay (P2Y12 Reaction Units, PRU) within 24 hours (h) following the placebo/clopidogrel LD (immediately prior to prasugrel LD), and at 2, 6, 24, 72 h following prasugrel LDs. The impact of CYP2C19 predicted metaboliser phenotype (extensive metaboliser [EM] and reduced metabolisers [RM]) on HPR status was also assessed. HPR (PRU ≥240) following the clopidogrel LD (prior to the prasugrel LD) was 58.5% in the combined clopidogrel LD groups. No significant difference was noted when stratified by time between the clopidogrel and prasugrel LDs (≤6 hs vs h). At 6 h following the 2nd loading dose in the combined prasugrel LD groups, HPR was 7.1%, with 0% HPR by 72 h. There was no significant effect of CYP2C19 genotype on pharmacodynamic (PD) response following either prasugrel LD treatments at any time point, regardless of whether it was preceded by a clopidogrel 600-mg LD. In conclusion, in this study, patients with ACS intended for PCI showed a high prevalence of HPR after clopidogrel 600-mg LD regardless of metaboliser status. When prasugrel LD was added, HPR decreased substantially by 6 h, and was not seen by 72 h.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2008
DOI: 10.1161/STROKEAHA.106.476648
Abstract: Background and Purpose— A previous randomized, placebo-controlled, double-blind study suggested that abciximab may be safe and effective in treatment of acute ischemic stroke. The current phase 3 study was planned to test the relative efficacy and safety of abciximab in patients with acute ischemic stroke with planned treatment within 5 hours since symptoms onset. Methods— An international, randomized, placebo-controlled, double-blind phase 3 trial tested intravenous administration of abciximab in 2 study cohorts using stratification variables of time since onset and stroke severity. The planned enrollment was 1800 patients. The primary cohort enrolled those patients who could be treated within 5 hours of onset of stroke. A companion cohort enrolled patients that were treated 5 to 6 hours after stroke as well as a smaller cohort of patients who could be treated within 3 hours of stroke present on awakening. The primary efficacy measure was the dichotomous modified Rankin Scale score at 3 months as adjusted to the baseline severity of stroke among subjects in the primary cohort. The primary safety outcome was the rate of symptomatic or fatal intracranial hemorrhage that occurred within 5 days of stroke. Results— The trial was terminated prematurely after 808 patients in all cohorts were enrolled by recommendation of an independent safety and efficacy monitoring board due to an unfavorable benefit-risk profile. At 3 months, approximately 33% of patients assigned placebo (72/218) and 32% of patients assigned abciximab (71/221 P =0.944) in the primary cohort were judged to have a favorable response to treatment. The distributions of outcomes on the modified Rankin Scale were similar between the treated and control groups. Within 5 days of enrollment, ≈5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intracranial hemorrhage ( P =0.002). The trial also did not demonstrate an improvement in outcomes with abciximab among patients in the companion and wake-up cohorts. Although the number of patients was small, an increased rate of hemorrhage was noted within 5 days among patients in the wake-up population who received abciximab (13.6% versus 5% for placebo). Conclusions— This trial did not demonstrate either safety or efficacy of intravenous administration of abciximab for the treatment of patients with acute ischemic stroke regardless of end point or population studied. There was an increased rate of symptomatic or fatal intracranial hemorrhage in the primary and wake-up cohorts.
Publisher: Elsevier BV
Date: 03-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2015
DOI: 10.1161/CIRCOUTCOMES.114.001223
Abstract: Nonadherence to prescribed evidence-based medications after acute myocardial infarction (MI) can contribute to worse outcomes and higher costs. We sought to better understand the modifiable factors contributing to early nonadherence of evidence-based medications after acute MI. We assessed 7425 acute MI patients treated with percutaneous coronary intervention at 216 US hospitals participating in TReatment with ADP receptor iNhibitorS: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) between April 2010 and May 2012. Using the validated Morisky instrument to assess cardiovascular medication adherence at 6 weeks post MI, we stratified patients into self-reported high (score, 8), moderate (score, 6–7), and low (score, ) adherence groups. Moderate and low adherence was reported in 25% and 4% of patients, respectively. One third of low adherence patients described missing doses of antiplatelet therapy at least twice a week after percutaneous coronary intervention. Signs of depression and patient-reported financial hardship because of medication expenses were independently associated with a higher likelihood of medication nonadherence. Patients were more likely to be adherent at 6 weeks if they had follow-up appointments made before discharge and had a provider explain potential side effects of their medications. Lower medication adherence may be associated with a higher risk of 3-month death/readmission (adjusted hazard ratio, 1.35 95% confidence interval, 0.98–1.87) although this did not reach statistical significance. Even early after MI, a substantial proportion of patients report suboptimal adherence to prescribed medications. Tailored patient education and pre discharge planning may represent actionable opportunities to optimize patient adherence and clinical outcomes. URL: www.clinicaltrials.gov . Unique identifier: NCT01088503.
Publisher: Elsevier BV
Date: 04-2014
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.JCIN.2015.08.018
Abstract: The purpose of this study was to determine whether bleeding risk varies depending on which P2Y12 receptor inhibitor agent is used. Prior studies have shown significant bleeding risk among patients treated with triple therapy (i.e., oral anticoagulant, P2Y12 receptor inhibitor, and aspirin). We evaluated patients with acute myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) at 233 hospitals in the United States enrolled in the TRANSLATE-ACS (Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study (April 2010 to October 2012). Using inverse probability-weighted propensity modeling, we compared 6-month adjusted risks of Bleeding Academic Research Consortium (BARC) bleeding, stratifying by whether or not bleeding was associated with rehospitalization among patients discharged on aspirin + anticoagulant + clopidogrel (triple-C), aspirin + anticoagulant + prasugrel (triple-P), aspirin + clopidogrel (dual-C), or aspirin + prasugrel (dual-P). Of 11,756 MI patients, 526 (4.5%) were discharged on triple-C, 91 (0.8%) on triple-P, 7,715 (66%) on dual-C, and 3,424 (29%) on dual-P. Compared with dual-therapy patients, triple-therapy patients had significantly higher any BARC-defined bleeding. Triple-P was associated with a greater risk of any BARC-defined bleeding events compared with triple-C. This finding was driven mostly by an increased risk of bleeding events that were patient-reported only and did not require rehospitalization. There were no significant differences in bleeding requiring rehospitalization between the triple-P and -C groups. Among MI patients, the addition of an oral anticoagulant was associated with a significantly greater risk of any BARC-defined bleeding relative to dual antiplatelet therapy, regardless of which P2Y12 receptor inhibitor was selected. Among patients on triple therapy, prasugrel use was associated with higher patient-reported-only bleeding, but not bleeding requiring rehospitalization, than clopidogrel-treated patients.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.JCIN.2009.11.012
Abstract: The aim of this study was to assess the risk-benefit of enoxaparin (Sanofi-Aventis, Paris, France) in primary percutaneous coronary intervention (PCI). Randomized studies have demonstrated the superiority of enoxaparin over unfractionated heparin (UFH) in acute ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytics. In the FINESSE (Facilitated INtervention with Enhanced Reperfusion Speed to Stop Events) trial--a double-blind, placebo-controlled study-2,452 patients with STEMI were randomized to primary PCI or facilitated PCI with abciximab alone or with half-dose reteplase. In this prospective FINESSE substudy, centers pre-specified use of either enoxaparin (0.5 mg/kg intravenous [IV], 0.3 mg/kg subcutaneous [SC]) or UFH (40 U/kg IV, 3,000 U maximum) with PCI. A logistic-regression model and a propensity multivariate model, both adjusted for baseline variables, were used to evaluate primary safety and secondary efficacy end points for enoxaparin versus UFH. Enoxaparin was administered to 759 patients and UFH to 1,693 patients. Nonintracranial Thrombolysis In Myocardial Infarction (TIMI) major/minor bleeding was not significantly different, but lower nonintracranial TIMI major bleeding was found with enoxaparin (2.6% vs. UFH 4.4%, logistic-regression adjusted odds ratio [OR]: 0.55 95% confidence interval [CI]: 0.31 to 0.99, p = 0.045), whereas intracranial hemorrhage was similar (0.27% vs. 0.24%, adjusted OR: 1.03 95% CI: 0.11 to 9.68, p = 0.980). Lower death, myocardial infarction, urgent revascularization, or refractory ischemia through 30 days was also associated with enoxaparin (5.3%) versus UFH (8.0%, adjusted OR: 0.47, 95% CI: 0.31 to 0.72, p = 0.0005) as was all-cause mortality through 90 days (3.8% vs. 5.6%, respectively, adjusted OR: 0.59, 95% CI: 0.35 to 0.99, p = 0.046). End points evaluating the net clinical benefit also significantly favored enoxaparin over UFH. Enoxaparin seems to be associated with a lower risk of cardiovascular outcomes compared with UFH in patients with STEMI undergoing primary PCI. Confirmation of these findings in a randomized study is warranted. (A Study of Abciximab and Reteplase When Administered Prior to Catheterization After a Myocardial Infarction [Finesse] NCT00046228).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2008
DOI: 10.1161/STROKEAHA.107.508853
Abstract: Background and Purpose— Approximately 10% to 20% of patients with a new stroke have symptoms present on awakening (wake-up stroke), but these persons are not treated with interventions to restore perfusion because the time of onset is not known. We elected to test the safety and possible efficacy of abciximab in treatment of enrolled subjects with wake-up stroke. Methods— Abciximab in Emergency Stroke Treatment Trial-II (AbESTT-II) tested the usefulness of abciximab in improving outcomes after acute ischemic stroke and it prospectively tested an intervention in subjects that awakened with their stroke. We compared the outcomes among the subjects in the wake-up group with the other subjects in the trial. Results— Of the 801 subjects randomized in the trial, 43 (22 abciximab and 21 placebo) had wake-up strokes. Those with wake-up strokes had similar baseline characteristics as the other subjects except for a higher rate of a new stroke found on CT. Recruitment of patients into the wake-up group was halted early because of the rate of bleeding with abciximab exceeded the prespecified safety margins (3 of 22 [13.6%]) within 5 days or at discharge versus 15 of 375 (4.0%) for the nonwake-up group ( P =0.07). Favorable outcomes at 3 months, as defined by scores on the modified Rankin Scale, among the wake-up group (4 of 43 [9.3%]) were worse than the nonwake-up group (221 of 758 [29.2%] P =0.005). Conclusions— Although the baseline characteristics of the wake-up group of subjects were similar to those of persons enrolled in the nonwake-up group, their outcomes were much poorer. Patients with wake-up stroke may not tolerate reperfusion therapies even when started within a short time of awakening.
Publisher: Elsevier BV
Date: 03-2015
Publisher: Wiley
Date: 2001
DOI: 10.1002/1099-1166(200112)16:1+<::AID-GPS571>3.0.CO;2-5
Abstract: Olanzapine (OLZ) is unique among currently available antipsychotic medications in its antagonism of a range of receptor systems including dopamine, norepinephrine, serotonin, acetylcholine, and histamine. Olanzapine's mechanistic complexity provides a broad efficacy profile in patients with schizophrenia and acute, pure or mixed mania. Patients experience symptomatic relief of mania, anxiety, hallucinations, delusions, and agitation/aggression and reduced depressive, negative, and some cognitive symptoms. This paper will review the safety profile of OLZ, focusing on the elderly, where data are available. Preclinical and clinical studies of OLZ are reviewed, with emphasis on its possible effects on the cholinergic system and the histamine H(1) receptor. Weight change and related metabolic considerations, cardiac and cardiovascular safety, and motor function during treatment with OLZ are also reviewed. In vitro receptor characterization methods, when done using physiologically relevant conditions allow accurate prediction of the relatively low rate of anticholinergic-like adverse events, extrapyramidal symptoms, and cardiovascular adverse events during treatment with OLZ. Currently available clinical data suggest olanzapine is predictably safe in treating adult patients of any age with schizophrenia and acute bipolar mania, as well as in treatment of patients with some types of neurodegenerative disorders.
Publisher: Elsevier BV
Date: 02-1998
Publisher: Cold Spring Harbor Laboratory
Date: 05-2023
DOI: 10.1101/2023.04.28.23289293
Abstract: Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled blood pressure (BP) despite using ≥3 antihypertensive classes or controlled BP while using ≥4 antihypertensive classes. Patients with aTRH have a higher risk for adverse cardiovascular outcomes compared to patients with controlled hypertension. Although there have been prior reports on the prevalence, characteristics, and predictors of aTRH, these have been broadly derived from smaller datasets, randomized controlled trials, or closed healthcare systems. We extracted patients with hypertension defined by ICD 9 and 10 codes during 1/1/2015-12/31/2018, from two large electronic health record databases: the OneFlorida Data Trust (n=223,384) and Research Action for Health Network (REACHnet) (n=175,229). We applied our previously validated aTRH and stable controlled hypertension (HTN) computable phenotype algorithms and performed univariate and multivariate analyses to identify the prevalence, characteristics, and predictors of aTRH in these real-world populations. The prevalence of aTRH in OneFlorida (16.7%) and REACHnet (11.3%) was similar to prior reports. Both populations had a significantly higher proportion of black patients with aTRH compared to those with stable controlled HTN. aTRH in both populations shared similar significant predictors, including black race, diabetes, heart failure, chronic kidney disease, cardiomegaly, and higher body mass index. In both populations, aTRH was significantly associated with similar comorbidities, when compared with stable controlled HTN. In two large, erse real-world populations, we observed similar comorbidities and predictors of aTRH as prior studies. In the future, these results may be used to improve healthcare professionals’ understanding of aTRH predictors and associated comorbidities. Prior studies of apparent treatment resistant hypertension have focused on cohorts from smaller datasets, randomized controlled trials, or closed healthcare systems. We used validated computable phenotype algorithms for apparent treatment resistant hypertension and stable controlled hypertension to identify the prevalence, characteristics, and predictors of apparent treatment resistant hypertension in two large, erse real-world populations. Large, erse real-world populations showed a similar prevalence of aTRH, 16.7% in OneFlorida and 11.3% in REACHnet, compared to those observed from other cohorts. Patients classified as apparent treatment resistant hypertension were significantly older and had a higher prevalence of comorbid conditions such as diabetes, dyslipidemia, coronary artery disease, heart failure with preserved ejection fraction, and chronic kidney disease stages 1-3. Within erse, real-world populations, the strongest predictors for apparent treatment resistant hypertension were black race, higher body mass index, heart failure, chronic kidney disease, and diabetes.
Publisher: Wiley
Date: 1295
Publisher: Oxford University Press (OUP)
Date: 20-01-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-08-2001
Abstract: Background — Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro) improves the clinical outcomes of percutaneous coronary intervention. This registry was conducted to characterize the effects of repeated administration of abciximab during intervention. Methods and Results — We recruited 500 consecutive patients at 22 centers in the United States who were receiving abciximab for at least a second time during percutaneous coronary intervention. Safety was measured as the incidence of hypersensitivity reactions, major bleeding, and thrombocytopenia. Efficacy was assessed as event-free clinical success. Human antichimeric antibody (HACA) responses were also characterized. There were no cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients (4.6% 95% CI, 2.8% to 6.4%), including 12 (2.4% 95% CI, 1.1% to 3.7%) who developed profound thrombocytopenia ( ×10 9 cells/L). In 2 patients (0.4%), profound thrombocytopenia did not develop until after hospital discharge in 4 (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a first readministration, a positive HACA titer was present in 22 of 454 patients (4.8%) after a first readministration, an additional 82 of 432 (19.0%) became HACA-positive. HACA did not neutralize the in vitro inhibition of platelet aggregation by abciximab or correlate with clinical events. Conclusions — The results, including overall rates of thrombocytopenia, were consistent with randomized clinical trials of first abciximab treatment. However, there was a shift from mild to profound thrombocytopenia, and cases of delayed presentation and of recurrent thrombocytopenia were seen. These findings suggest that indications and guidelines for first-time use apply to retreatment, particularly the systematic monitoring for thrombocytopenia.
Publisher: Springer Science and Business Media LLC
Date: 22-05-2013
DOI: 10.1007/S40256-013-0028-1
Abstract: To measure the adherence and persistence of patients with acute coronary syndrome (ACS) initiating prasugrel after percutaneous coronary intervention (PCI). Using the Thomson Reuters MarketScan Commercial and Medicare Supplemental database, a retrospective cohort study identified patients initiating prasugrel following ACS-PCI hospitalization in 2009-2011. Prasugrel adherence over 12 months was measured using the medication possession ratio (MPR) predictors of adherence were identified using a logistic regression model. Persistence was defined as time on continuous therapy a Cox model identified predictors of prasugrel discontinuation. Among 1,340 patients, the mean age was 57 years 79.5 % were male. Median prasugrel MPR was 93.2 % 69.0 % of patients had an MPR ≥80 %. Predictors of adherence <80 % included prior PCI [odds ratio (OR) 0.60 95 % confidence interval (CI) 0.40-0.90], prior depression (OR 0.37 95 % CI 0.16-0.84), prior bleeding (OR 0.41 95 % CI 0.19-0.86), and baseline anticoagulant use (OR 0.13 95 % CI 0.03-0.55). Baseline statin use predicted higher adherence (OR 1.56 95 % CI 1.21-2.02). The median duration of prasugrel therapy was 259 days. Predictors of discontinuation included prior anemia [hazard ratio (HR) 1.63 95 % CI 1.21-2.21], prior cardiomyopathy (HR 2.72 95 % CI 1.44-5.13), and prior ischemic heart disease (HR 1.15 95 % CI 1.00-1.32) baseline statin use predicted reduced risk of discontinuation (HR 0.85 95 % CI 0.75-0.97). Although adherence to prasugrel was generally high, the duration of therapy was frequently below recommendations. An awareness of risk factors for low adherence or early discontinuation can point to appropriate targets for intervention.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2011
Publisher: Informa Healthcare
Date: 18-07-2014
DOI: 10.1185/03007995.2014.941055
Abstract: To compare 30 and 90 day real-world acute myocardial infarction (AMI) and bleeding related rehospitalization rates in acute coronary syndrome (ACS) patients receiving percutaneous coronary intervention (PCI ACS-PCI) treated with clopidogrel or prasugrel. Using the Premier hospital database, ACS-PCI patients receiving a drug-eluting (DES) or bare-metal (BMS) stent and clopidogrel or prasugrel from July 2009 to June 2011 were analyzed. Patients were included based on the prasugrel US prescribing information (USPI), excluding patients with a history of transient ischemic attack/stroke and patients ≥75 years without diabetes or prior MI. The primary endpoint was 30 day adjusted AMI rehospitalization rate. Secondary endpoints included 90 day AMI and 30 and 90 day bleeding-related rehospitalization rates. Treatment comparisons were adjusted using propensity score stratification. At the index event, prasugrel patients (N = 9404) differed from clopidogrel patients (N = 74,163) by having a lower risk of comorbid conditions associated with bleeding, being more likely younger and male, having ST-elevation MI and receiving a DES. For clopidogrel and prasugrel, respectively, the observed AMI-related rehospitalization rates were 4.7% and 3.9% at 30 days (p < 0.0001) and 6.3% and 5.1% at 90 days (p < 0.0001). After adjustment, prasugrel was associated with ∼10% lower odds of AMI-related rehospitalization (30 days: OR = 0.892 [95% CI: 0.798, 0.998] 90 days, OR = 0.901 [95% CI: 0.817, 0.994]). Adjusted bleeding-related rehospitalization rates were similar to each other (OR = 1.035 at 30 days [95% CI: 0.765, 1.399] OR = 0.922 at 90 days [95% CI: 0.725, 1.172]). Treatment adherence was not assessed. Bleeding events not resulting in a hospitalization (e.g. office, outpatient, or emergency room visits), deaths outside the hospital, or readmissions to a hospital outside of the Premier alliance were not captured in the database. The different patient characteristics between prasugrel- and clopidogrel-treated patients suggest physicians are more selective in choosing patients for prasugrel than recommended in the prasugrel USPI. However, after adjustment for these differences, 30 and 90 day AMI rehospitalization rates were lower for prasugrel-treated patients compared to clopidogrel-treated patients, with no difference in adjusted bleeding-related rehospitalization rates.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-07-2015
DOI: 10.1161/CIRCULATIONAHA.114.014992
Abstract: Aspirin is the most widely used antiplatelet drug postmyocardial infarction, yet its optimal maintenance dose after percutaneous coronary intervention with stenting remains uncertain. We compared outcomes of 10 213 patients with myocardial infarction who underwent percutaneous coronary intervention and were discharged on dual-antiplatelet therapy at 228 US hospitals in the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Major adverse cardiovascular events and bleeding within 6 months postdischarge were compared between high-dose (325 mg) and low-dose aspirin (81 mg) by using regression models with inverse probability-weighted propensity adjustment. Overall, 6387 patients (63%) received high-dose aspirin at discharge. Major adverse cardiovascular events risk was not significantly different between groups (high versus low: unadjusted 8.2% versus 9.2% adjusted hazard ratio, 0.99 95% confidence interval, 0.85–1.17). High-dose aspirin use was associated with greater risk of any Bleeding Academic Research Consortium–defined bleeding events (unadjusted 24.2% versus 22.7% adjusted odds ratio, 1.19 95% confidence interval, 1.06–1.33), driven mostly by minor Bleeding Academic Research Consortium type 1 or 2 bleeding events not requiring hospitalization (unadjusted 21.4% versus 19.5% adjusted odds ratio, 1.19 95% confidence interval, 1.05–1.34). Bleeding events requiring hospitalization were similar by aspirin dosing groups (unadjusted 2.8% versus 3.2%, adjusted odds ratio, 1.22 95% confidence interval, 0.87–1.70). Similar associations were observed in landmark analyses accounting for aspirin dosing change over time, and across subgroup analyses by age, sex, baseline aspirin use, and type of ADP receptor inhibitor (clopidogrel versus prasugrel/ticagrelor). Among percutaneous coronary intervention–treated patients with myocardial infarction, high-maintenance-dose aspirin was associated with similar rates of major adverse cardiovascular events, but a greater risk of minor bleeding than those discharged on low-dose aspirin.
Publisher: Wiley
Date: 18-11-2015
DOI: 10.1002/CCD.26279
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.AHJ.2011.08.021
Abstract: Platelet inhibition is critical in reducing both short- and long-term atherothrombotic risks after acute myocardial infarction (MI), especially among patients managed with percutaneous coronary intervention (PCI). Currently available antiplatelet medications, including adenosine diphosphate (ADP) receptor inhibitors, have demonstrated variability in efficacy and safety in clinical trials, yet few studies have examined contemporary "real-world" approaches to platelet inhibition and associated outcomes. TRANSLATE-ACS is a prospective observational study that will track up to 17,000 MI patients managed with PCI, from the inhospital to outpatient settings for up to 12 months postdischarge to provide a comprehensive picture of current treatment patterns and outcomes in routine clinical practice. TRANSLATE-ACS exemplifies a collaborative study design that efficiently builds upon a well-established PCI registry platform, and yet, through a systematic telephone interview follow-up process, provides important longitudinal clinical and economic follow-up capacity through 15 months after initial MI hospitalization. Furthermore, TRANSLATE-ACS incorporates a hospital-level, clustered, randomized substudy to investigate the impact of point-of-care platelet inhibition testing on subsequent patient management. Finally, TRANSLATE-ACS provides feedback through quarterly reports to participating sites on their care practices benchmarked to peer performance to support and promote longitudinal quality of cardiovascular care delivery. TRANSLATE-ACS not only addresses important clinical and scientific questions but also includes pioneering design features that will assist in the evolution of clinical registries.
Publisher: Elsevier BV
Date: 09-1999
DOI: 10.1016/S0002-9149(99)00421-X
Abstract: We investigated the effect of platelet fibrinogen receptor blockade on infarct size after primary angioplasty. Abciximab significantly reduced the time-to-peak creatine kinase without affecting enzymatic infarct size, suggesting a beneficial effect on the pattern and speed of reperfusion.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-02-2009
DOI: 10.1161/CIRCULATIONAHA.108.817577
Abstract: Background— The Raloxifene Use for The Heart (RUTH) trial showed that raloxifene, a selective estrogen receptor modulator, had no overall effect on the incidence of coronary events in women with established coronary heart disease or coronary heart disease risk factors. We provide detailed results of the effect of raloxifene on coronary outcomes over time and for 24 subgroups (17 predefined, 7 post hoc). Methods and Results— Postmenopausal women (n=10 101 mean age, 67 years) were randomized to raloxifene 60 mg/d or placebo for a median of 5.6 years. Coronary outcomes were assessed by treatment group in women with coronary heart disease risk factors and those with established coronary heart disease. Raloxifene had no effect on the incidence of coronary events in any subgroup except in the case of a post hoc age subgroup analysis using age categories defined in the Women’s Health Initiative randomized trials. The effect of raloxifene on the incidence of coronary events differed significantly by age (interaction P =0.0118). The incidence of coronary events in women years of age was significantly lower in those assigned raloxifene (50 events) compared with placebo (84 events hazard ratio, 0.59 95% confidence interval, 0.41 to 0.83 P =0.003 absolute risk reduction, 36 per 1000 women treated for 1 year). No difference was found between treatment groups in the incidence of coronary events in women ≥60 and or ≥70 years of age. Conclusions— In postmenopausal women at increased risk of coronary events, the overall lack of benefit of raloxifene was similar across the prespecified subgroups.
Publisher: Elsevier BV
Date: 02-1998
Publisher: Elsevier BV
Date: 04-2004
Publisher: Springer Science and Business Media LLC
Date: 10-09-2015
DOI: 10.1007/S40256-015-0147-Y
Abstract: Our objective was to compare 1-year real-world healthcare resource utilization (HRU), associated charges, and antiplatelet treatment patterns among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with ticagrelor or prasugrel. Using the ProMetis-Lx database, adult ACS-PCI patients treated with ticagrelor or prasugrel post-discharge were identified between 1 August 2011 and 31 May 2013 and propensity matched to adjust for baseline differences. Before matching, ticagrelor-treated patients (n = 2991) were older with increased baseline ischemic and bleeding risks compared with prasugrel-treated patients (n = 12,797). After matching, ticagrelor patients had higher all-cause HRU (2.5 vs. 2.4 per patient per month P = 0.012) and cardiovascular (CV) HRU (0.4 vs. 0.3 per patient per month P = 0.026), with the difference in CV rehospitalizations (17.7 vs. 15.7 % P = 0.011) primarily driven by congestive heart failure (CHF) (4.9 vs. 3.8 % P = 0.02). All-cause charges within 1 year did not significantly differ between groups ($US5456 vs. 4844 per patient per month P = 0.37), but dyspnea-related total charges were significantly higher with ticagrelor ($US139 vs. 95 per patient per month P = 0.005). Although infrequent, switching was slightly higher with ticagrelor (8.3 vs. 6.0 % P < 0.001) at 1 year, and mean persistence was slightly longer with prasugrel (150 vs. 159 days P = 0.002), with no significant difference in mean adherence (61 vs. 63 % P = 0.17). Overall monthly HRU was slightly lower with prasugrel than with ticagrelor, with no significant difference in bleeding HRU. Prasugrel was associated with slightly higher pharmacy charges, but lower dyspnea charges, resulting in no significant difference in total charges. Patients receiving prasugrel tended to use it for longer than those receiving ticagrelor as less switching occurred. These findings may aid decision making, but must be tempered due to inherent study limitations.
Publisher: Elsevier BV
Date: 10-2003
DOI: 10.1016/S0002-9149(03)00882-8
Abstract: Early complications may h er efforts to hasten discharge after primary percutaneous coronary intervention (PCI) for myocardial infarction (MI). Glycoprotein IIb/IIIa inhibitors, by reducing early recurrent ischemia, may aid in these efforts. We examined whether adjunctive abciximab could accelerate discharge and reduce costs within a trial of primary PCI after acute MI. The CADILLAC trial randomized 2,082 patients with MI to 1 of 4 reperfusion strategies in a 2 x 2 factorial design: angioplasty, angioplasty with abciximab, stent implantation, or stenting with abciximab. Patients randomized to abciximab had postprocedural heparin withheld, and discharge scheduled for days 1.5 to 2 (low-risk patients) or days 2 to 3 (high-risk patients) after MI if they were stable. Other patients were discharged at the physician's discretion. Abciximab treatment was associated with significant reductions in the primary end points of in-hospital death, reinfarction, ischemic target vessel revascularization (TVR), or disabling stroke (5.6% vs 2.7%, p = 0.003)--largely reflecting reduced ischemic TVR (3.8% vs 1.4%, p = 0.002)--and in early subacute thrombosis (1.3% vs 0.2%, p = 0.01). Hospitalization was significantly shorter in abciximab-treated patients (median 3.1 vs 3.5 days, p <0.001), but total in-hospital costs did not differ significantly (13,413 +/- 5,309 US dollars vs 13,000 +/- 6,006 US dollars, p = 0.13). Rates of the composite end point did not differ significantly during the week after discharge (0.8% vs 0.2%, p = 0.10), nor did component event rates. Abciximab during primary PCI is associated with fewer early adverse outcomes, likely contributing to offset its cost. Hospitalizations after primary PCI are so short, however, that efforts to accelerate discharge with abciximab appear unfeasible, and overall costs remain unchanged.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2023
DOI: 10.1161/ATVBAHA.122.318748
Abstract: Thrombo-inflammation is central to COVID-19-associated coagulopathy. TF (tissue factor), a driver of disordered coagulation and inflammation in viral infections, may be a therapeutic target in COVID-19. The safety and efficacy of the novel TF inhibitor rNAPc2 (recombinant nematode anticoagulation protein c2) in COVID-19 are unknown. ASPEN-COVID-19 was an international, randomized, open-label, active comparator clinical trial with blinded end point adjudication. Hospitalized patients with COVID-19 and elevated D-dimer levels were randomized 1:1:2 to lower or higher dose rNAPc2 on days 1, 3, and 5 followed by heparin on day 8 or to heparin per local standard of care. In comparisons of the pooled rNAPc2 versus heparin groups, the primary safety end point was major or nonmajor clinically relevant International Society of Thrombosis and Haemostasis bleeding through day 8. The primary efficacy end point was proportional change in D-dimer concentration from baseline to day 8, or discharge if before day 8. Patients were followed for 30 days. Among 160 randomized patients, median age was 54 years, 43.1% were female, and 38.8% had severe baseline COVID-19. There were no significant differences between rNAPc2 and heparin in bleeding or other safety events. Overall, median change in D-dimer was −16.8% (interquartile range, −45.7 to 36.8 P =0.41) with rNAPc2 treatment and −11.2% (−36.0 to 34.4 P =0.91) with heparin ( P intergroup =0.47). In prespecified analyses, in severely ill patients, D-dimer levels tended to increase more within the heparin (median, 29.0% [−14.9 to 145.2] P =0.02) than the rNAPc2 group (median, 25.9% [−49.1 to 136.4] P =0.14 P intergroup =0.96) in mildly ill patients, D-dimer levels were reduced within each group with a numerically greater reduction with rNAPc2 versus heparin (rNAPc2 median, −32.7% [−44.7 to 4.3] P =0.007 and heparin median, −16.8% [−36.0 to 0.5] P =0.008, P intergroup =0.34). rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8. URL: www.clinicaltrials.gov Unique identifier: NCT04655586.
Publisher: Elsevier BV
Date: 09-2000
Abstract: We examined the ex vivo platelet aggregation profiles of patients who underwent percutaneous coronary intervention and received either abciximab, ticlopidine, or both agents. The trial was a prospective, nonrandomized, single-center, open-label study of 42 patients undergoing percutaneous coronary intervention who received the following regimens: group 1, abciximab (0.25 mg/kg bolus and 12-hour, 0.125 microg/kg per minute infusion) group 2, ticlopidine (250 mg twice daily for 14 consecutive days, initiated 12 to 18 hours before intervention) group 3, abciximab plus ticlopidine initiated 12 to 18 hours before procedure and group 4, abciximab plus ticlopidine initiated 72 to 96 hours before procedure. Platelet aggregation measurements to adenosine diphosphate (ADP) and a thrombin receptor activating peptide (TRAP, 8 micromol/L) were obtained before ticlopidine treatment, after initiation of ticlopidine, and immediately before abciximab treatment and intervention, then at several time periods after onset of abciximab treatment. Platelet surface abciximab levels were monitored by flow cytometry. Neither ticlopidine regimen resulted in appreciable platelet inhibition before intervention and before administration of abciximab. In the ticlopidine-only arm, suppression of platelet aggregation to the weakest stimuli (5 micromol/L ADP 23% +/- 7.5%) was detected within 24 hours after intervention, with maximal inhibition to both 5 and 20 micromol/L ADP observed 7 days after intervention (48% +/- 7.9% and 18% +/- 8.7%, respectively). In contrast, ticlopidine marginally suppressed TRAP-mediated platelet activation at times when maximal effects on ADP-mediated platelet aggregation were evident. Neither ticlopidine regimen appreciably enhanced platelet inhibition during or shortly after cessation of abciximab treatment. For all 3 abciximab treatment arms, profound inhibition of ADP-induced (>80%) and TRAP-induced (>65%) platelet aggregation was observed 2 hours after treatment. In the abciximab-only arm, platelet aggregation responses gradually recovered, with the rate of response directly proportional to the strength of stimuli. However, in the ticlopidine plus abciximab arms, recovery of platelet aggregation at later times (7 and 14 days) reached a plateau and reflected the extent of inhibition observed in ticlopidine-treated patients. No difference in the clearance of surface-bound abciximab from circulating platelets was observed between the abciximab and abciximab plus ticlopidine arms. Concomitant abciximab plus ticlopidine treatment yields a platelet inhibition profile that is a composite of the effects of the 2 agents. In the early stages of treatment, inhibition of ex vivo platelet aggregation was mediated primarily by abciximab effects were more moderate and were predominately mediated by ticlopidine.
Publisher: Elsevier BV
Date: 02-1998
Publisher: Wiley
Date: 24-05-2016
DOI: 10.1002/CCD.26606
Abstract: Young women undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) experience greater adverse events than men, potentially due to under-treatment. We sought to compare the 1-year outcomes by sex in patients ≤55 years of age from a contemporary PCI cohort. PROMETHEUS was a retrospective multicenter observational US study comparing outcomes in clopidogrel and prasugrel treated patients following ACS PCI. MACE was defined as a composite of death, myocardial infarction, stroke or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Hazard ratios were generated using multivariable Cox proportional hazards regression. The study cohort included 4,851 patients of which 1,162 (24.0%) were women and 3,689 (76.0%) were men. In this cohort, the prevalence of diabetes (41.0 vs. 27.9%) and chronic kidney disease (12.7 vs. 7.2%) was higher among women compared with men. Irrespective of sex, prasugrel was used in less than one-third of patients (31.8% in men vs. 28.1% in women, P = 0.01). Unadjusted, 1-year MACE (21.1% vs. 16.2%, P < 0.001) and bleeding (3.6% vs. 2.2%, P = 0.01) was significantly higher in women compared with men, but these results were no longer significant after adjustment for risk (HR 1.13, 95% CI 0.94-1.36 for MACE and HR 1.31, 95% CI 0.85-2.04 for bleeding). Women ≤ 55 years of age undergoing ACS PCI have significantly greater comorbidities than young men. Despite a higher risk clinical phenotype in women, prasugrel use was significantly lower in women than men. Female sex was associated with a significantly higher risk of 1-year MACE and bleeding than male sex, findings that are attributable to baseline differences. © 2016 Wiley Periodicals, Inc.
Publisher: Wiley
Date: 23-09-2018
DOI: 10.1002/CCD.27816
Abstract: Concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and P2Y We studied 11,781 myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI) at 233 hospitals in the TRANSLATE ACS study (2010-2012). We used propensity matching to compare 6-week major adverse cardiac events (MACE: death, recurrent MI, stroke, or unplanned revascularization) and BARC 2+ bleeding events between patients who did and did not receive planned GPI. Planned and bailout GPI were used in 4,983 (42.2%) and 229 (4.4%) MI patients undergoing PCI, respectively. Patients receiving planned GPI were younger (58 vs. 61 years), more likely to present with STEMI (62.6% vs. 45.4%) or have stent thrombosis (4.2% vs. 2.1%, all P < 0.001) than those without planned GPI use. Planned GPI was used less often with prasugrel/ticagrelor versus clopidogrel (37.1% vs. 43.3%), or when any P2Y Planned GPI use as reported by practicing physicians was prevalent between 2010 and 2012 and was associated with increased risk of bleeding but not lower MACE.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.AHJ.2015.06.021
Abstract: Although platelet function and pharmacogenomic testing have been studied in clinical trials, their adoption into contemporary practice is unknown. We studied patterns of platelet function and pharmacogenomic testing among 10,048 patients with acute myocardial infarction treated with percutaneous coronary intervention at 226 US hospitals in the TRANSLATE-ACS observational study between April 2010 and October 2012, excluding those receiving research protocol-mandated testing. Inverse probability-weighted propensity adjustment was used to compare 1-year bleeding and major adverse cardiac event risks between patients with and without testing. Overall, 337 (3.4%) patients underwent predischarge platelet function testing, whereas 85 (0.9%) underwent pharmacogenomic testing 82% and 93% of hospitals never performed any platelet function or pharmacogenomic testing, respectively. Patients undergoing testing were more likely to be on an adenosine diphosphate receptor inhibitor preadmission or to have percutaneous coronary intervention of a previously treated lesion. Tested patients were more likely than nontested patients to be switched from clopidogrel to prasugrel/ticagrelor (25.7% vs 9.7%, P < .001) and were more likely to be on prasugrel/ticagrelor 6 months postdischarge (33.8% vs 25.1%, P < .001). No significant differences in 1-year bleeding and major adverse cardiac event risks were observed between tested and nontested patients (adjusted hazard ratios 1.06 [95% CI 0.68-1.65] and 1.21 [95% CI 0.94-1.54], respectively). Platelet function and pharmacogenomic testing are rarely performed in contemporary myocardial infarction patients in the United States. When tested, patients were more likely to be treated with higher-potency adenosine diphosphate receptor inhibitors, yet no significant differences in longitudinal outcomes were observed.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2013
DOI: 10.1161/CIRCINTERVENTIONS.112.000063
Abstract: Adding a prasugrel loading dose (LD) to a clopidogrel LD could be desirable because clopidogrel may fail to provide adequate levels of platelet inhibition in patients with acute coronary syndrome undergoing percutaneous coronary intervention. The pharmacodynamic response of prasugrel 60 mg LD alone was compared with prasugrel 60 mg or 30 mg added ≤24 hours to clopidogrel 600 mg in Transferring from Clopidogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome Patients study—a multicenter, randomized, double-blind, double-dummy, 3-arm, parallel, active-comparator controlled study. Two hundred eighty-two patients were randomized to 3 LD strategies: placebo plus prasugrel 60 mg, clopidogrel 600 mg plus prasugrel 60 mg, or clopidogrel 600 mg plus prasugrel 30 mg. Platelet function was assessed using VerifyNow P2Y12 Reaction Units (PRU) immediately before prasugrel LD, and 2, 6, 24, and 72 hours after prasugrel LD in 149 patients with evaluable platelet function studies. At 6 hours after the prasugrel 60 mg LD, the least squares mean (95% confidence interval) difference between placebo rasugrel 60 mg and clopidogrel 600 mg rasugrel 60 mg (primary outcome) was 22.2 (−11.0 to 55.5 P =0.19 least squares mean PRU 57.9 versus 35.6, respectively). For clopidogrel 600 mg rasugrel 30 mg (least squares mean PRU, 53.9), the difference was 3.9 (−28.2 to 36.1 P =0.81) versus placebo rasugrel 60 mg. No significant differences in PRU were observed at any time point across the 3 groups. There were few bleeding events observed regardless of treatment. Platelet reactivity with prasugrel 60 mg LD added to clopidogrel 600 mg LD was not significantly different compared with prasugrel 60 mg LD alone in acute coronary syndrome patients undergoing percutaneous coronary intervention. URL: www.clinicaltrials.gov . Unique identifier: NCT01115738.
Publisher: Elsevier BV
Date: 02-1998
Publisher: Elsevier BV
Date: 11-2008
Publisher: Wiley
Date: 12-1999
DOI: 10.1002/(SICI)1522-726X(199912)48:4<430::AID-CCD20>3.0.CO;2-G
Abstract: The efficacy of abciximab and moderate dose heparin in attaining reperfusion in acute MI was tested in a multicenter pilot study. Patients with acute MI of less than 6-hr onset triaged to primary PTCA received intravenous abciximab bolus and infusion and heparin (70 u/kg) in the emergency room. Mean time to angiography from administration of abciximab was 34 +/- 23 min. TIMI flow rates were: grade 0-62%, grade I-20%, grade II-9%, and grade III-9%. Primary PTCA was performed with 100% success rate. Access site bleeding occurred in 10% of patients with no incidence of intracranial bleeding. TIMI II/III flow rates were 50% in a patient subset where angiography was delayed by 45 min. While not an alternative to thrombolytics in AMI, abciximab administration in the emergency room in patients triaged to PTCA may be beneficial in situation where door to needle time is delayed as TIMI II/III flows may be attained in some patients. Cathet. Cardiovasc. Intervent. 48:430-434, 1999.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2015
DOI: 10.1161/CIRCINTERVENTIONS.114.001712
Abstract: Little is known about how clinicians use platelet function testing to guide choice and dosing of adenosine diphosphate receptor inhibitor (ADPri) therapy in routine community practice. The Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (ACS)—Prospective, Open Label, Antiplatelet Therapy Study (TRANSLATE-POPS) was a cluster-randomized trial in which 100 hospitals were assigned access to no-cost platelet function testing versus usual care for acute myocardial infarction patients treated with percutaneous coronary intervention. In both arms, ADPri treatment decisions were left up to the care team. The primary end point was the frequency of ADPri therapy adjustment before discharge. Secondary end points included 30-day rates of major adverse cardiovascular events and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries–defined bleeding events. Platelet function testing was performed in 66.9% of patients treated in intervention sites versus 1.4% of patients in usual care sites. Intervention arm patients were more likely to have ADPri therapy adjustment than usual care patients (14.8% versus 10.5%, P =0.004 odds ratio 1.68, 95% confidence interval 1.18–2.40) however, there were no significant differences in 30-day major adverse cardiovascular events (4.8% versus 5.4%, P =0.73 odds ratio 0.94, 95% confidence interval 0.66–1.34) or bleeding (4.3% versus 4.2%, P =0.33 odds ratio 0.86, 95% confidence interval 0.55–1.34). One-year outcomes were also not significantly different between groups. An as-treated analysis showed higher incidence of ADPri therapy adjustment among intervention arm patients who received platelet function testing than untested usual care arm (16.4% versus 10.2%, P .0001), but no significant differences in major adverse cardiovascular events or bleeding. TRANSLATE-POPS found that when clinicians routinely used platelet function testing, they were more likely to adjust their choice or dosing of ADPri therapy yet with few changes in therapy overall, significant differences in clinical outcomes were not seen. URL: www.clinicaltrials.gov . Unique identifier: NCT01088503.
No related grants have been discovered for Mark B Effron.