Clinical Research
Interventional Cardiology
Impact of Platelet Reactivity on Clinical Outcomes After Percutaneous Coronary Intervention: A Collaborative Meta-Analysis of Individual Participant Data

https://doi.org/10.1016/j.jacc.2011.06.059Get rights and content
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Objectives

The purpose of the study was to systematically evaluate the significance of platelet reactivity on clopidogrel treatment on adverse cardiovascular events using a collaborative meta-analysis using patient-level data for the VerifyNow P2Y12 assay (Accumetrics, San Diego, California).

Background

Clinical evidence has been controversial regarding the influence of clopidogrel on treatment platelet reactivity and ischemic outcomes.

Methods

MEDLINE, Scopus, and the Cochrane library databases were searched through January 2010. A database containing individual patient-level time-to-event data was generated from identified studies. The primary outcome of interest was a composite of death, myocardial infarction (MI), or stent thrombosis. Secondary outcomes included the incidence of: 1) death; 2) MI; and 3) stent thrombosis.

Results

A total of 6 studies with 3,059 patients was included. In each study, clopidogrel responsiveness was assessed using the same point-of-care assay after percutaneous coronary intervention. The primary endpoint occurred more frequently in higher quartiles of P2Y12 reaction unit (PRU) values: quartile I, 5.8%; quartile II, 6.9%; quartile III, 10.9%; quartile IV, 15.8% (p < 0.001). Taking quartile I as referent, the hazard ratios (HRs) for the primary endpoint were as follows: quartile II, HR: 1.13 (95% confidence interval [CI]: 0.72 to 1.78; p = 0.60); quartile III, HR: 1.82 (95% CI: 1.20 to 2.75; p = 0.005); quartile IV, HR: 2.62 (95% CI: 1.78 to 3.87; p < 0.001). On a continuous scale, every 10-U increase in PRU was associated with a significantly higher rate of the primary endpoint (HR: 1.04; 95% CI: 1.03 to 1.06; p < 0.0001). According to receiver-operating characteristic curve analysis, a PRU value of 230 appeared to best predict death, MI, or stent thrombosis (p < 0.001). A PRU value ≥230 was associated with a higher rate of the composite primary endpoint (HR: 2.10; 95% CI: 1.62 to 2.73; p < 0.0001), as well as the individual endpoints of death (HR: 1.66; 95% CI: 1.04 to 2.68; p = 0.04), MI (HR: 2.04; 95% CI: 1.51 to 2.76; p < 0.001), and stent thrombosis (HR: 3.11; 95% CI: 1.50 to 6.46; p = 0.002).

Conclusions

In this collaborative meta-analysis, the level of on-treatment platelet reactivity according to the P2Y12 assay is associated with long-term cardiovascular events after percutaneous coronary intervention, including death, MI, and stent thrombosis.

Key Words

clopidogrel
meta-analysis
percutaneous coronary intervention
platelet reactivity
stent thrombosis

Abbreviations and Acronyms

AUC
area under the curve
CI
confidence interval
HR
hazard ratio
IDI
integrated discrimination improvement
MI
myocardial infarction
NRI
net reclassification improvement
PCI
percutaneous coronary intervention
PRU
P2Y12 reaction unit(s)

Cited by (0)

Dr. Brar has received Speakers' Bureau fees from and consulted for Accumetrics (<$5,000). Dr. ten Berg has received Speakers' Bureau fees from Sanofi-Aventis, Eli Lilly and Co., Bristol-Myers Squibb, and Merck and Co.; and has provided consultancy services for Sanofi-Aventis, Eli Lilly and Co., Schering-Plough, and GlaxoSmithKline. Dr. Marcucci has received Speakers' Bureau fees from DSI/Lilly and Merck and Co. Dr. Price has received research grants from Bristol-Myers Squibb, Sanofi-Aventis, and Accumetrics; has received Speakers' Bureau fees from DSI/Lilly; and has provided consultancy services for DSI/Lilly, AstraZeneca, Accumetrics, Sanofi-Aventis, and The Medicines Co. Dr. Valgimigli has received research grants and honoraria for lectures and for advisory boards from Iroko, Eli Lilly, Terumo, The Medicines Co., Abbott, Eisai, AstraZeneca, Cordis, and Medtronic; and honoraria for lectures and/or advisory boards from Cordis, Medtronic, Abbott, EISAI, Merck, AstraZeneca, and The Medicines Co. Dr. Breet has received speaker fees from Siemens. Dr. Dangas has received lecture honoraria from Continuing Medical Education programs funded by grants from Sanofi-Aventis and Bristol-Myers Squibb (modest level); has provided consultancy services for AstraZeneca (modest level); has received a fellowship program grant from Accumetrics; and has received speaker honoraria from Cordis/J&J and AstraZeneca. All other authors have reported that they have no relationships relevant to this paper to disclose.