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Thromb Haemost 2016; 115(04): 823-825
DOI: 10.1160/TH15-09-0742
Atherosclerosis and Ischaemic Disease
Schattauer GmbH

Vascular risk levels affect the predictive value of platelet reactivity for the occurrence of MACE in patients on clopidogrel

Systematic review and meta-analysis of individual patient data
Jean-Luc Reny
1   Geneva Platelet Group, School of Medicine, University of Geneva, Geneva, Switzerland
2   Division of Internal Medicine and Rehabilitation, Trois-Chéne Hospital, Geneva University Hospitals, Geneva, Switzerland
,
Pierre Fontana
1   Geneva Platelet Group, School of Medicine, University of Geneva, Geneva, Switzerland
3   Division of Angiology and Haemostasis, Geneva University Hospitals, Geneva, Switzerland
,
Willibald Hochholzer
4   Universitaets Herzzentrum Freiburg-Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Franz Josef Neumann
4   Universitaets Herzzentrum Freiburg-Bad Krozingen, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany
,
Jurrién ten Berg
5   St Antonius Hospital, Nieuwegein, the Netherlands
,
Paul W. Janssen
5   St Antonius Hospital, Nieuwegein, the Netherlands
,
Tobias Geisler
6   Department of Cardiology, University Hospital Tübingen, Tübingen, Germany
,
Meinrad Gawaz
6   Department of Cardiology, University Hospital Tübingen, Tübingen, Germany
,
Rossella Marcucci
7   Center for Atherothrombotic diseases, Department of Experimental and Clinical Medicine, University of Florence, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
,
Anna-Maria Gori
7   Center for Atherothrombotic diseases, Department of Experimental and Clinical Medicine, University of Florence, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
,
Thomas Cuisset
8   Cardiologie Interventionnelle, CHU Timone Unité Inserm UMR 626, Faculté de Médecine Marseille, France
,
Marie-Christine Alessi
9   UMR Inserm 1062, inra 1260, université Aix-Marseille, France
,
Philippe Berdagué
10   Division of Cardiology, Beziers Hospital, Béziers, France
,
Paul A. Gurbel
11   Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland, USA
,
Gerald Yong
12   Royal Perth Hospital, Perth, Western Australia, Australia
,
Dominick J. Angiolillo
13   Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA
,
Daniel Aradi
14   Department of Cardiology, Heart Center Balatonfüred, Hungary
,
Roy Beigel
15   The Leviev Heart Center, Sheba Medical Center, Tel-Hashomer, and the Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
,
Gianluca Campo
16   Cardiovascular Institute, Azienda Ospedaliera Universitaria di Ferrara, Cona (FE), Italy
,
Christophe Combescure
17   Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland
18   Center of Clinical Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland
› Author Affiliations Financial support: This study was supported by grants French ministry of health PHRC 15–07 to JL Reny “Etudes prospectives sur la réponse biologique au clopidogrel et évènements ischémiques chez les patients athérothrombotiques : Métaanalyse sur données individuelles et résumées” (http://www.plan-alzheimer.gouv.fr/IMG/pdf/Liste_des_dossiers_retenus_-_2_mai_2008.pdf) and the Geneva University Hospitals. Conducted within the Geneva Platelet Group and the division of Clinical Epidemiology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Further Information

Publication History

Received: 20 September 2015

Accepted after minor revision: 22 October 2015

Publication Date:
29 November 2017 (online)

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Summary

Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral. The role and usefulness of PR with regard to levels of cardiovascular risk are unclear. We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischaemic strokes, and vascular deaths) in relation to PR and its interaction with cardiovascular risk levels. PR was determined using ADP-induced light transmission aggregometry with a primary concentration of 20 μM ADP. Thirteen prospective studies totaled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5 %) during a median follow-up of 12 months. The strength of the association between the risk of MACE and PR increased significantly (p=0.04) with the number of risk factors present (age> 75 years, ACS at inclusion, diabetes, and hypertension). No association was detected in patients with no risk factor (p=0.48). In patients presenting one risk factor, only high-PR was associated with an increased risk of MACE (HR 3.2, p=0.001). In patients presenting ≥ 2 risk factors, the increase of risk started from medium-PR (medium-PR: HR=2.9, p=0.0004; high-PR: HR=3.7, p=0.0003). PR allowed the reclassification of 44 % of the total population to a different risk level for the outcome of MACE, mostly in intermediate or high risk patients. In conclusion, the magnitude of the association between PR and MACE risk is strongly dependent on the level of cardiovascular risk faced by patients on clopidogrel.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Clopidogrel - drug response - platelets - cardiovascular diseases - ischaemic events

 

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