Comparison of Platelet Function Tests in Predicting Clinical Outcome in Patients Undergoing Coronary Stent Implantation
- Nicoline J. Breet, MD;
- Jochem W. van Werkum, MD, PhD;
- Heleen J. Bouman, MSc;
- Johannes C. Kelder, MD;
- Henk J. T. Ruven, PhD;
- Egbert T. Bal, MD;
- Vera H. Deneer, PharmD, PhD;
- Ankie M. Harmsze, PharmD;
- Jan A. S. van der Heyden, MD;
- Benno J. W. M. Rensing, MD, PhD;
- Maarten J. Suttorp, MD, PhD;
- Christian M. Hackeng, PhD;
- Jurriën M. ten Berg, MD, PhD
- Author Affiliations: Departments of Cardiology (Drs Breet, van Werkum, Kelder, Bal, van der Heyden, Rensing, Suttorp, and ten Berg and Ms Bouman), Clinical Chemistry (Drs Ruven and Hackeng), and Clinical Pharmacy (Drs Deneer and Harmsze), St Antonius Hospital; and St Antonius Center for Platelet Function Research (Drs Breet, van Werkum, Kelder, Deneer, Harmsze, Hackeng, and ten Berg and Ms Bouman), Nieuwegein, the Netherlands.
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
