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Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis
Francesco Sofi1, Rossella Marcucci, Anna Maria Gori
1Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. francescosofi@gmail.com
Insights
Patients with coronary artery disease (CAD) unresponsive to clopidogrel have a significantly higher risk of death and cardiovascular events. This meta-analysis confirms that poor response to clopidogrel treatment increases adverse outcomes.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Clopidogrel is a key antiplatelet medication for patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).
- Non-responsiveness to clopidogrel, indicated by residual platelet reactivity, may increase the risk of adverse cardiovascular events.
- Previous studies have explored this association, necessitating an updated meta-analysis to consolidate current evidence.
Purpose of the Study:
- To update the clinical evidence on the relationship between clopidogrel non-responsiveness and clinical outcomes in CAD patients post-PCI.
- To assess the risk of death and adverse coronary events in patients exhibiting residual platelet reactivity despite clopidogrel treatment.
Main Methods:
- A comprehensive meta-analysis was conducted using data from MEDLINE, EMBASE, Web of Science, and the Cochrane Library up to January 2009.
- Included studies were prospective cohort studies analyzing clopidogrel responsiveness in CAD patients and their association with mortality and thrombotic events.
- Fourteen studies, encompassing 4,564 patients, were analyzed, with sensitivity analyses performed to address heterogeneity and publication bias.
Main Results:
- The cumulative analysis of 14 studies revealed that residual platelet reactivity under clopidogrel treatment was significantly associated with an increased risk of death and/or thrombotic recurrences (OR 5.67, 95% CI 2.97 to 10.84).
- Exclusion of four heterogeneous studies due to publication bias risk did not alter the overall finding, with the adjusted analysis showing a significant increased risk (OR 3.58, 95% CI 2.54 to 5.05).
Conclusions:
- This updated meta-analysis confirms a significant association between poor response to clopidogrel and recurrent cardiovascular events in CAD patients.
- The findings underscore the clinical relevance of monitoring platelet reactivity and tailoring antithrombotic therapy for optimal patient outcomes.
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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