Comparison of Platelet Function Tests in Predicting Clinical Outcome in Patients Undergoing Coronary Stent Implantation

Abstract

Context: High on-treatment platelet reactivity is associated with atherothrombotic events following coronary stent implantation. Objective: To evaluate the capability of multiple platelet function tests to predict clinical outcome. Design, Setting, and Patients: Prospective, observational, single-center cohort study of 1069 consecutive patients taking clopidogrel undergoing elective coronary stent implantation between December 2005 and December 2007. On-treatment platelet reactivity was measured in parallel by light transmittance aggregometry, VerifyNow P2Y12 and Plateletworks assays, and the IMPACT-R and the platelet function analysis system (PFA-100) (with the Dade PFA collagen/adenosine diphosphate (ADP) cartridge and Innovance PFA P2Y). Cutoff values for high on-treatment platelet reactivity were established by receiver operating characteristic curve (ROC) analysis. Main Outcome Measurement: The primary end point was defined as a composite of all-cause death, nonfatal acute myocardial infarction, stent thrombosis, and ischemic stroke. The primary safety end point included TIMI (Thrombolysis In Myocardial Infarction) criteria major and minor bleeding. Results: Kaplan-Meier analysis demonstrated that at 1-year follow-up, the primary end point occurred more frequently in patients with high on-treatment platelet reactivity when assessed by light transmittance aggregometry (52 [11.7%; 95% confidence interval {CI}, 8.9%-15.0%] vs 36 [6.0%; 95% CI, 4.2%-8.2%] P < .001; n = 1049), VerifyNow (54 [13.3%; 95% CI, 10.2%-17.0%] vs 37 [5.7%; 95% CI, 4.1%-7.8%] P < .001; n = 1052), Plateletworks (33 [12.6%; 95% CI, 8.8%-17.2%] vs 21 [6.1%; 95% CI, 3.8%-9.2%] P = .005; n = 606), and Innovance PFA P2Y (18 [12.2%; 95% CI; 7.4%-18.6%] vs 28 [6.3%; 95% CI, 4.3%-8.9%] P = .02; n = 588). ROC-curve analysis demonstrated that light transmittance aggregometry (area under the curve [AUC], 0.63; 95% CI, 0.58-0.68), VerifyNow (AUC, 0.62; 95% CI, 0.57-0.67), and Plateletworks (AUC, 0.61; 95% CI, 0.53-0.69) had modest ability to discriminate between patients with and without primary end point at 1-year follow-up. The IMPACT-R (n = 905) and the Siemens PFA Collagen/ADP (n = 812) were unable to discriminate between patients with and without the primary end point at 1-year follow-up (all AUCs included 0.50 in the CI). None of the tests identified patients at risk for bleeding. Conclusions: Of the platelet function tests assessed, light transmittance aggregometry, VerifyNow, Plateletworks, and Innovance PFA P2Y were significantly associated with the primary end point. However, the predictive accuracy of these 4 tests was only modest. None of the tests provided accurate prognostic information to identify patients at higher risk of bleeding following stent implantation. Trial Registration: clinicaltrials.gov Identifier: NCT00352014