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

Study Questions:

What is the significance of platelet reactivity on clopidogrel treatment on adverse cardiovascular events?

Methods:

This is a collaborative meta-analysis using patient-level data for the VerifyNow P2Y12 assay. 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. Time-to-event data are reported and displayed using the Kaplan-Meier method, with comparisons between groups performed using the log-rank test.

Results:

A total of six studies with 3,059 patients were included. In each study, clopidogrel responsiveness was assessed using the same point-of-care assay after percutaneous coronary intervention (PCI). 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 ratio (HR) (95% confidence interval [CI]; p value) for the primary endpoint was as follows: quartile II (HR, 1.13; 95% CI, 0.72-1.78; p = 0.60), quartile III (HR, 1.82; 95% CI, 1.20-2.75; p < 0.005), and quartile IV (HR, 2.62; 95% CI, 1.78-3.87; 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, 1.03-1.06; 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, 2.13; 95% CI, 1.64-2.77; p < 0.0001), as well as the individual endpoints of death (HR, 1.68; 95% CI, 1.04-2.72; p = 0.03), MI (HR, 2.07; 95% CI, 1.53-2.80; p < 0.001), and stent thrombosis (HR, 2.65; 95% CI, 1.38-5.09; p < 0.003).

Conclusions:

The authors concluded that the level of on-treatment platelet reactivity according to the P2Y12 assay is associated with long-term cardiovascular events after PCI, including death, MI, and stent thrombosis.

Perspective:

The principal finding of this study is that higher on-treatment platelet reactivity measured using the VerifyNow P2Y12 assay was predictive of long-term ischemic events. Also, a PRU value of ≥230 was associated with higher rates of death, MI, or stent thrombosis. Additional intervention trials are required to better understand how platelet function testing can be integrated into the treatment of patients undergoing PCI, including in the acute coronary syndrome setting where prasugrel or ticagrelor is indicated. Pending such data, routine platelet function testing is not indicated.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Platelet Function Tests, Ticlopidine, Piperazines, Angioplasty, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Stents, Incidence, Thrombosis, Cardiovascular Diseases, Confidence Intervals


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