Clopidogrel non-responsiveness and risk of cardiovascular morbidity

Francesco Sofi; Rossella Marcucci; Anna Maria Gori; Betti Giusti; Rosanna Abbate; Gian Franco Gensini

doi:10.1160/TH09-06-0418

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(04): 00
DOI: 10.1160/TH09-06-0418

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Clopidogrel non-responsiveness and risk of cardiovascular morbidity

An updated meta-analysis

Francesco Sofi

¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero–Universitaria Careggi, Florence, Italy

²Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Italy

³Don Carlo Gnocchi Foundation, IRCCS, Florence, Italy

,

Rossella Marcucci

¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero–Universitaria Careggi, Florence, Italy

,

Anna Maria Gori

¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero–Universitaria Careggi, Florence, Italy

²Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Italy

³Don Carlo Gnocchi Foundation, IRCCS, Florence, Italy

,

Betti Giusti

¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero–Universitaria Careggi, Florence, Italy

,

Rosanna Abbate

¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero–Universitaria Careggi, Florence, Italy

,

Gian Franco Gensini

¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero–Universitaria Careggi, Florence, Italy

²Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Italy

³Don Carlo Gnocchi Foundation, IRCCS, Florence, Italy

› Author Affiliations

Abstract

Summary

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.

Keywords

Clopidogrel - antiplatelet therapy - clinical recurrences - meta-analysis

Full Text

References

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