Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: impact of prasugrel and high-dose clopidogrel.

OBJECTIVES: This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI).

BACKGROUND: The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown.

METHODS: Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel.

RESULTS: A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5%) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p < 0.0001). Compared with patients without HPR, the risk of all-cause death, myocardial infarction, stent thrombosis, or stroke at 1 year was significantly higher in the high-dose clopidogrel group (hazard ratio [HR]: 2.27; 95% confidence interval [CI]: 1.45 to 3.55; p < 0.0001), and patients who were switched to prasugrel had similar outcomes (HR: 0.90; 95% CI: 0.44 to 1.81; p = 0.76). Bleeding Academic Research Consortium (BARC) type 3/5 bleeding was also more frequent in patients treated with high-dose clopidogrel (HR: 2.09; 95% CI: 1.05 to 4.17; p = 0.04) than in patients switched to prasugrel (HR: 0.45; 95% CI: 0.11 to 1.91; p = 0.28). In a multivariate model, HPR with high-dose clopidogrel, but not with prasugrel, was an independent predictor of the composite ischemic endpoint (HR: 1.90; 95% CI: 1.17 to 3.08; p = 0.01).

CONCLUSIONS: Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.