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Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis.

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TLDR
A significant association between residual platelet reactivity under clopidogrel treatment and recurrent cardiovascular events is documents, suggesting the relevance of ongoing interventional studies aimed at tailoring the antithrombotic therapy in CAD patients.
Abstract
We performed this meta-analysis to update the clinical evidences on the relation between clopidogrel non-responsiveness and clinical outcomes in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention. An electronic literature search through MEDLINE, EMBASE, Web of Science, and the Cochrane Library and bibliographies of retrieved articles up to January, 2009 was conducted. Studies were included if they had a cohort prospective design, if they analysed clopidogrel responsiveness in CAD patients in relation to death and/or occurrence of adverse coronary events during follow-up, and if they reported an adequate statistical analysis. Fourteen studies, totalling 4,564 CAD patients followed for a time ranging from 14 days to one year, were included. The cumulative analysis reported that residual platelet reactivity despite clopidogrel treatment was significantly associated with an increased risk of death and/or thrombotic recurrences (odds ratio [OR] 5.67, 95% confidence interval [CI] 2.97 to 10.84; p<0.00001). However, four studies contributed to a consistent heterogeneity of the model and evidenced a significant risk of publication bias, so were excluded from the analysis. This exclusion, however, did not influence the overall result, by confirming the increased risk of cardiovascular recurrences for patients with a poor response to clopidogrel treatment (OR 3.58, 95%CI 2.54 to 5.05; p<0.00001). The present updated meta-analysis documents a significant association between residual platelet reactivity under clopidogrel treatment and recurrent cardiovascular events, so suggesting the relevance of ongoing interventional studies aimed at tailoring the antithrombotic therapy in CAD patients.

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Journal ArticleDOI

Paraoxonase-1 is a major determinant of clopidogrel efficacy

TL;DR: Using in vitro metabolomic profiling techniques, paraoxonase-1 (PON1) is identified as the crucial enzyme for clopidogrel bioactivation, with its common Q192R polymorphism determining the rate of active metabolite formation.
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Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

TL;DR: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.
Journal ArticleDOI

ACCF/AHA Clopidogrel Clinical Alert: Approaches to the FDA “Boxed Warning” A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association

TL;DR: The recent US Food and Drug Administration “boxed warning” on clopidogrel raises important questions for practitioners and patients and addresses the need for pharmacogenomic testing to identify patients’ altered clopinogrel metabolism and thus their risk for a suboptimal clinical response to clopIDogrel.
References
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Journal ArticleDOI

Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.

TL;DR: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation, however, the risk of major bleeding is increased among patients treated with clopIDogrel.
Journal Article

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events(CAPRIE).

Denis Clement
- 01 Jan 1996 - 
TL;DR: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death.
Journal ArticleDOI

Cytochrome P-450 Polymorphisms and Response to Clopidogrel

TL;DR: Carriers of a reduced-function CYP2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis, than did noncarriers.
Journal ArticleDOI

Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial

TL;DR: In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events in hospital, and should be considered routinely.
Journal ArticleDOI

Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation

TL;DR: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death as discussed by the authors.
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