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

Abstract

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.