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J Am Coll Cardiol. 2011 Nov 1;58(19):1945-54. doi: 10.1016/j.jacc.2011.06.059.

Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data.

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1
Kaiser Permanente, Regional Cardiac Cath Lab, 4867 Sunset Boulevard, Los Angeles, CA 90027, USA. SBrar@cvri.org

Abstract

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 P2Y(12) 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 P2Y(12) assay is associated with long-term cardiovascular events after percutaneous coronary intervention, including death, MI, and stent thrombosis.

Comment in

PMID:
22032704
DOI:
10.1016/j.jacc.2011.06.059
[Indexed for MEDLINE]
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