ORCID Profile
0000-0001-9651-7829
Current Organisation
University of Southampton
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2011
DOI: 10.1161/CIRCINTERVENTIONS.110.958512
Abstract: Controversy persists regarding the correct strategy for bifurcation lesions. Therefore, we combined the patient-level data from 2 large trials with similar methodology: the NORDIC Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study (BBC ONE). Both randomized trials compared simple (provisional T-stenting) versus complex techniques, using drug-eluting stents. In the simple group (n=457), 129 patients had final kissing balloon dilatation in addition to main vessel stenting, and 16 had T-stenting. In the complex group (n=456), 272 underwent crush, 118 culotte, and 59 T-stenting techniques. A composite end point at 9 months of all-cause death, myocardial infarction, and target vessel revascularization occurred in 10.1% of the simple versus 17.3% of the complex group (hazard ratio 1.84 [95% confidence interval 1.28 to 2.66], P =0.001). Procedure duration, contrast, and x-ray dose favored the simple approach. Subgroup analysis revealed similar composite end point results for true bifurcations (n=657, simple 9.2% versus complex 17.3% hazard ratio 1.90 [95% confidence interval 1.22 to 2.94], P =0.004), wide-angled bifurcations to 70° (n=217, simple 9.6% versus complex 15.7% hazard ratio 1.67 [ 95% confidence interval 0.78 to 3.62], P =0.186), large (≥2.75 mm) diameter side branches (n=281, simple 10.4% versus complex 20.7% hazard ratio 2.42 [ 95% confidence interval 1.22 to 4.80], P =0.011), longer length ( mm) ostial side branch lesions (n=464, simple 12.1% versus complex 19.1% hazard ratio 1.71 [95% confidence interval 1.05 to 2.77], P =0.029), or equivalent sized vessels (side branch .25 mm smaller than main vessel) (n=108, simple 12.0% versus complex 15.5% hazard ratio 1.35 [95% confidence interval 0.48 to 3.70], P =0.57). For bifurcation lesions, a provisional single-stent approach is superior to systematic dual stenting techniques in terms of safety and efficacy. A complex approach does not appear to be beneficial in more anatomically complicated lesions. URL: www.clinicaltrials.gov . Unique identifier: NCT 00376571 and NCT 00351260.
Publisher: American Medical Association (AMA)
Date: 2019
Publisher: Informa UK Limited
Date: 11-12-2017
DOI: 10.1080/09537104.2017.1392498
Abstract: The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB
Publisher: Wiley
Date: 04-05-2021
DOI: 10.1002/CCD.29702
Abstract: To describe outcomes following percutaneous coronary intervention (PCI) in patients who would usually have undergone coronary artery bypass grafting (CABG). In the United Kingdom, cardiac surgery for coronary artery disease (CAD) was dramatically reduced during the first wave of the COVID‐19 pandemic. Many patients with “surgical disease” instead underwent PCI. Between 1 March 2020 and 31 July 2020, 215 patients with recognized “surgical” CAD who underwent PCI were enrolled in the prospective UK‐ReVasc Registry (ReVR). 30‐day major cardiovascular event outcomes were collected. Findings in ReVR patients were directly compared to reference PCI and isolated CABG pre‐COVID‐19 data from British Cardiovascular Intervention Society (BCIS) and National Cardiac Audit Programme (NCAP) databases. ReVR patients had higher incidence of diabetes (34.4% vs 26.4%, P = .008), multi‐vessel disease with left main stem disease (51.4% vs 3.0%, P .001) and left anterior descending artery involvement (94.8% vs 67.2%, P .001) compared to BCIS data. SYNTAX Score in ReVR was high (mean 28.0). Increased use of transradial access (93.3% vs 88.6%, P = .03), intracoronary imaging (43.6% vs 14.4%, P .001) and calcium modification (23.6% vs 3.5%, P .001) was observed. No difference in in‐hospital mortality was demonstrated compared to PCI and CABG data (ReVR 1.4% vs BCIS 0.7%, P = .19 vs NCAP 1.0%, P = .48). Inpatient stay was half compared to CABG (3.0 vs 6.0 days). Low‐event rates in ReVR were maintained to 30‐day follow‐up. PCI undertaken using contemporary techniques produces excellent short‐term results in patients who would be otherwise CABG candidates. Longer‐term follow‐up is essential to determine whether these outcomes are maintained over time.
Publisher: Wiley
Date: 25-05-2018
Abstract: There is potential value in testing in idual response to P2Y12 inhibitors to predict ischemic and bleeding risk in patients undergoing percutaneous coronary intervention. The aims of this study were: (1) to validate the ability of a novel point of care (POC) assay, thrombelastography (TEG) 6s, to detect changes in adenosine diphosphate (ADP)-induced whole blood clotting in volunteers and patients given clopidogrel using TEG 5000 as a reference and (2) to compare a novel, rapid parameter, area under the curve at 15 minutes (AUC15), with the traditional maximum clot litude (MA) in TEG 6s. A total of 25 participants were included in whom ADP-induced clotting was measured at 4 time points: (1) 12 healthy volunteers given 600 mg of clopidogrel (2) 12 patients with ACS given 600 mg of clopidogrel (3) 1 healthy volunteer given 600 mg of clopidogrel on 5 separate occasions. All s les were tested using conventional TEG 5000 and the new POC TEG 6S, and a new parameter called AUC15 was compared with MA in TEG 6s. (1) TEG 5000 and TEG 6s both detected changes in ADP-induced platelet activation. Bland-Altman analysis demonstrated a good level of agreement between them. (2) For TEG 6S, correlation between MA and the novel AUC15 was strong for both thrombin and ADP channels (R Thrombelastography 6s is a rapid, easy to use and accurate test of ADP-induced clotting using TEG 5000 as a reference. A novel parameter, AUC15, is a viable, time-saving option for this test and has potential value in personalized P2Y12 inhibitor therapy.
Publisher: BMJ
Date: 18-10-2010
Abstract: Aspirin is now widely accepted as the first-line antithrombotic platelet therapy for at-risk in iduals. During the last decade or so it has also become established that co-administering antagonists of the ADP receptor P2Y(12) with aspirin further reduces the risk of acute thrombotic events. By the nature of its evolution, this therapeutic approach assumes that P2Y(12) receptor antagonists will be added to aspirin, and this therefore dominates the design of clinical trials. This strategy has resulted in the generation of a large body of clinical evidence showing the benefit of aspirin plus P2Y(12) receptor antagonists, largely from studies with clopidogrel and more recently from those with prasugrel and ticagrelor, but with obvious limitations in terms of residual ischaemic event rates and bleeding complications. It is our hypothesis, however, that when administered in the presence of potent P2Y(12) receptor antagonists, aspirin could actually increase total cardiovascular risk, although this has never been tested in large outcome studies. Clearly, this potentially negative interaction could be of relevance to millions of patients.
Publisher: National Institute for Health and Care Research
Date: 11-2020
DOI: 10.3310/EME07050
Abstract: Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction and is independently associated with adverse outcomes. To determine whether or not a strategy involving low-dose intracoronary fibrinolytic therapy infused early after coronary reperfusion will reduce microvascular obstruction. This was a multicentre, randomised, double-blind, parallel-group, placebo-controlled, dose-ranging trial. The trial took place at 11 hospitals in the UK between 17 March 2016 and 21 December 2017. Patients with acute ST-segment elevation myocardial infarction and a symptom onset to reperfusion time of ≤ 6 hours were eligible for randomisation. Radial artery access was a requirement, and further angiographic criteria included a proximal-to-middle coronary artery occlusion or impaired coronary flow in the presence of a definite thrombus in the culprit coronary artery. Exclusion criteria included a functional coronary collateral supply to the infarct-related artery, any contraindication to fibrinolysis and lack of informed consent. Additional exclusion criteria for safety were (1) requirement for immunosuppressive drug therapy for ≤ 3 months and (2) treatment with an antimicrobial agent. A total of 440 participants were randomly assigned 1 : 1 : 1 to treatment with placebo ( n = 151), 10 mg of alteplase ( n = 144) or 20 mg of alteplase ( n = 145) administered by manual infusion directly into the infarct-related coronary artery over 5–10 minutes. The intervention was scheduled to happen after reperfusion and before stent implantation. The primary outcome was the amount of microvascular obstruction (percentage of left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging at 2–7 days after enrolment. The primary analysis was the comparison between the 20 mg of alteplase group and the placebo group if this comparison was not significant, the comparison of the 10 mg of alteplase group with the placebo group was considered as a secondary analysis. A total of 618 patients (minimum of 558 patients). Recruitment was halted on 21 December 2017 given that conditional power for the primary outcome based on a prespecified analysis of the first 267 randomised participants was 30% in both treatment groups (futility criterion). The primary outcome was compared between groups using a stratified Wilcoxon rank-sum test (van Elteren test), stratified by the location of the myocardial infarction. Among the 440 patients (mean age of 60.5 years 15% women), the primary end point was measured in 396 (90%) patients, 17 (3.9%) withdrew, seven died and all other patients were followed up to 3 months. The amount (mean percentage of left ventricular mass) of microvascular obstruction was 2.3% versus 2.6% versus 3.5% in the placebo, 10 mg of alteplase and 20 mg of alteplase groups, respectively. In the primary analysis, microvascular obstruction did not differ between the 20 mg of alteplase group and the placebo group: 3.5% versus 2.3%, estimated difference 1.16% (95% confidence interval –0.08% to 2.41% p = 0.32). In the secondary analysis, microvascular obstruction did not differ between the 10 mg of alteplase group and the placebo group: 2.6% versus 2.3%, estimated difference 0.29% (95% confidence interval –0.76% to 1.35% p = 0.74). By 3 months, major adverse cardiac events (cardiac death, non-fatal myocardial infarction and unplanned hospitalisation for heart failure) had occurred in 15 (10.1%) patients in the placebo group, 18 (12.9%) in the 10 mg of alteplase group and 12 (8.2%) in the 20 mg of alteplase group. Adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction compared with placebo. Premature discontinuation of enrolment limited the power of the secondary and safety analyses. Low-dose intracoronary alteplase or tenecteplase could be compared with placebo at the end of primary percutaneous coronary intervention in patients with an ischaemic time of 4 hours. This trial is registered as ClinicalTrials.gov NCT02257294. This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation Vol. 7, No. 5. See the NIHR Journals Library website for further project information.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JACC.2019.10.033
Abstract: Randomized trials have shown that complete revascularization in patients with ST-segment elevation myocardial infarction (MI) with multivessel disease results in lower major adverse cardiovascular events (MACE) (all-cause death, MI, ischemia-driven revascularization, heart failure). The goal of this study was to determine whether the benefits of complete revascularization are sustained long-term and their impact on hard endpoints. CvLPRIT (Complete versus Lesion-only Primary PCI Trial) was a randomized trial of complete inpatient revascularization versus infarct-related artery revascularization only at the index admission. Randomized patients have been followed longer-term. The components of the original primary endpoint were collected from physical and electronic patient records, and from local databases for all readmissions. The median follow-up (achieved in >90% patients) from randomization to first event or last follow-up was 5.6 years (0.0 to 7.3 years). The primary MACE endpoint rate at this time point was 24.0% in the complete revascularization group but 37.7% of the infarct-related artery-only group (hazard ratio: 0.57 95% confidence interval: 0.37 to 0.87 p = 0.0079). The composite endpoint of all-cause death/MI was 10.0% in the complete revascularization group versus 18.5% in the infarct-related artery-only group (hazard ratio: 0.47 95% confidence interval: 0.25 to 0.89 p = 0.0175). In a landmark analysis (from 12 months to final follow-up), there was no significant difference between MACE, death/MI, and in idual components of the primary endpoint. Long-term follow-up of the CvLPRIT trial shows that the significantly lower rate of MACE in the complete revascularization group, previously seen at 12 months, is sustained to a median of 5.6 years. A significant difference in composite all-cause death/MI favoring the complete revascularization was also observed. (Complete versus Lesion-only Primary PCI Trial ISRCTN70913605).
Publisher: Informa UK Limited
Date: 10-12-2016
DOI: 10.1080/14779072.2017.1266255
Abstract: Platelets play a key role in pathogenesis of atherothrombosis. Activated platelets initiate thrombus formation. Antiplatelet therapy (APT) modifies these properties. APT involves aspirin. The existence of 'aspirin resistance' is reported in many populations with cardiovascular disease. The prevalence of this phenomenon is highly variable, affecting more than 50% of patient subgroups in some papers. Areas covered: This review describes the prevalence of 'aspirin resistance', analyses why there is so much apparent variation and addresses whether the commonly used tests of aspirin response are in fact accurately assessing its functional performance. The clinical consequences if arachidonic acid(AA)-mediated assays do not accurately assess the functional performance of aspirin could be important. Expert commentary: Two important issues arise, firstly, that it can no longer be considered robust to use AA-induced platelet activation as a true diagnostic test of functional response to aspirin. It is clear that the output from PFT using AA as an agonist are not even a surrogate for the pharmacological activity of aspirin. Secondly, current data raise important and clinically relevant questions about, how AA stimulation induces clotting in in iduals in whom aspirin is effective at its COX-1 target. The evidence indicates at least one recruitable, COX-1-independent pathway that is associated with vascular inflammation.
Publisher: BMJ
Date: 2022
DOI: 10.1136/OPENHRT-2021-001783
Abstract: To estimate the population prevalence and treatable burden of severe aortic stenosis (AS) in the UK. We adapted a contemporary model of the population profile of symptomatic and asymptomatic severe AS in Europe and North America to estimate the number of people aged ≥55 years in the UK who might benefit from surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). With a point prevalence of 1.48%, we estimate that 291 448 men and women aged ≥55 years in the UK had severe AS in 2019. Of these, 68.3% (199 059, 95% CI 1 77 201 to 221 355 people) would have been symptomatic and, therefore, more readily treated according to their surgical risk profile the remaining 31.7% of cases (92 389, 95% CI 70 093 to 144 247) being asymptomatic. Based on historical patterns of intervention, 58.4% (116 251, 95% CI 106 895 to 1 25 606) of the 199 059 symptomatic cases would qualify for SAVR, with 7208 (95% CI 7091 to 7234) being assessed as being in a high, preoperative surgical risk category. Among the remaining 41.6% (82 809, 95% CI 73 453 to 92 164) of cases potentially unsuitable for SAVR, an estimated 61.7% (51 093, 95% CI 34 780 to 67 655) might be suitable for TAVI. We estimate that 172 859 out of 291 448 prevalent cases of severe AS (59.3%) will subsequently die within 5 years without proactive management. These data suggest a high burden of severe AS in the UK requiring surgical or transcatheter intervention that challenges the ongoing capacity of the National Health Service to meet the needs of those affected.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2020
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Nick Curzen.