Abstract 19827

Vascular Risk Levels Affect the Predictive Value of Platelet Reactivity for the Occurrence of Major Adverse Cardiovascular Events in Patients on Clopidogrel Systematic Review and Collaborative Meta-analysis of Individual Patient Data

Reny, Jean-Luc
Fontana, Pierre
Hochholzer, Willibald
Neumann, Franz-Josef
ten Berg, Jurren
Janssen, Paul
Geisler, Tobias
Gawaz, Meinrad
Marcucci, Rossella
Gori, Ana-Maria
Cuisset, Thomas
Alessi, Marie-Christine
Gurbel, Paul
Berdagué, Philippe
Yong, Gerald
Angiolillo, Dominick
Aradi, Daniel
Beigel, Roy
Campo, Gianluca
Campo, Gianluca
Combescure, Christophe

¹Internal Medicine, Rehabilitation and Geriatrics, Geneva Universtiy Hosps, Thônex-Geneva, Switzerland
²Angiology and Hemostasis, Geneva Universtiy Hosps, Geneva, Switzerland
³Klinik für Kardiologie und Angiologie II, Herzzentrum Freiburg-Bad Krozingen, Bad Krozingen, Germany
⁴Cardiology, St Antonius Hosp, Nieuwegein, Netherlands
⁵Dept of cardiology, Univ Hosp Tübingen,, Tübingen, Germany
⁶Cntr for atherothrombotic diseases, Dept Experimental and Clinical Medicine,, Univ of Florence, Florence, Italy
⁷Cardiologie Interventionnelle, CHU Timone Unité Inserm UMR 626, Faculté de Médecine, Marseille, France
⁸Sinai Cntr for Thrombosis Rsch,, Sinai Hosp of Baltimore, Baltimore, MD
⁹Cardiology, Béziers Hosp, Béziers, France
¹⁰Cardiology, Maryland Royal Perth Hosp, Perth, Australia
¹¹Cardiology, Univ of Florida College of Medicine,, Jacksonville, FL
¹²Dept of cardiology, Heart Cntr Balatonfüred, Balatonfüred, Hungary
¹³The Leviev Heart Cntr,, Sheba Med Cntr, Tel-Hashomer, and the Sackler Faculty of Medicine, Tel Aviv Univ, Tel Aviv, Israel
¹⁴Cardiovascular Institute, Azienda Ospedaliera Universitaria di Ferrara, Cona, Italy
¹⁵Clinical Epidemiology, Geneva Universtiy Hosps, Geneva, Switzerland

Author Disclosures: J. Reny: Honoraria; Modest; MSD speaker’s fee. P. Fontana: Research Grant; Modest; Evolva, Astra Zeneca. W. Hochholzer: None. F. Neumann: None. J. ten Berg: Consultant/Advisory Board; Modest; Astra Zeneca,, Daiichi Sankyo, Merck, Eli Lilly,. P. Janssen: None. T. Geisler: Consultant/Advisory Board; Modest; Eli Lilly, Daiichi Sankyo, BMS, Pfizer,. M. Gawaz: Consultant/Advisory Board; Modest; Bayer,, Astra Zeneca,, MSD., Lilly. R. Marcucci: None. A. Gori: None. T. Cuisset: None. M. Alessi: Consultant/Advisory Board; Modest; Astra Zeneca,, Eli Lilly,. P. Gurbel: Consultant/Advisory Board; Modest; Daiichi Sankyo,, Sankyo,, Lilly,, Bayer,, AstraZeneca,, Accumetrics,, Merck,, Medtronic,. P. Berdagué: None. G. Yong: None. D. Angiolillo: Consultant/Advisory Board; Modest; Bristol-Myers Squibb,, Sanofi-Aventis,, Eli Lilly,, Daiichi Sankyo, Inc.,, The Medicines Company,, AstraZeneca,, Merck,, Evolva,, Abbott Vascular,, and PLx Pharma. D. Aradi: Consultant/Advisory Board; Modest; Verum Diagnostica,, Roche,, DSI/Lilly,, Bayer,, Astra-Zeneca,, Pfizer,, Biotronic,, Abbott. R. Beigel: None. G. Campo: None. G. Campo: None. C. Combescure: None.

Circulation 130(Suppl_2):p A19827, November 25, 2014.

Introduction: 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.

Hypothesis: The clinical relevance of PR in predicting MACE varies according to patients’ cardiovascular risk levels.

Methods: We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischemic 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 20μM ADP.

Results: Thirteen prospective cohort studies totalled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5%) during a median follow-up of 12 months. The risk of MACE associated with PR increased differentially according to the number of risk factors present (age>75 years, ACS at inclusion, diabetes, and hypertension; interaction p=0.04): no association to PR in low-risk patients (no risk factor) (p=0.48); 3.2 times greater risk of MACE in high PR (> 60%) intermediate-risk patients (one risk factor) (p=0.001); 2.9 and 3.7 times greater risk of MACE in medium PR (41%-60%) and high PR (>60%) high-risk patients (≥2 risk factors) (p=0.0004 and 0.0003, respectively). These interactions followed the same trends in studies using 5μM ADP.

Conclusions: The magnitude of the association between PR and MACE risk is strongly dependant on the level of cardiovascular risk faced by patients on clopidogrel suggesting that PR-tailored strategies may be most effective in higher-risk patients.