Comparison of methods to determine platelet reactivity under treatment with aspirin

Abstract

Insufficient response to aspirin is associated with increased cardiovascular risk, but its prognostic relevance in patients receiving potent P2Y12 inhibitors remains uncertain. We assessed methods to identify high on-treatment platelet reactivity (HTPR) under aspirin and evaluated the impact of potent versus less potent P2Y12 inhibition in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Platelet function was analyzed in 757 aspirin-pretreated CAD patients treated with clopidogrel ( n  = 406), ticagrelor ( n  = 152), or prasugrel ( n  = 165). Antiplatelet efficacy was assessed using multiple electrode aggregometry (MEA), platelet function analyzer-100 (PFA-100 ® ), cone and platelet analyzer (CPA), and serum thromboxane B2 (TXB2). All-cause mortality was assessed over five years, and major bleeding and major adverse cardiac events (MACE) over one year. AA-induced MEA > 6 U was associated with higher long-term mortality, however, discriminatory performance was modest (AUC = 0.575, p  = 0.051), while CPA-SC < 6% strongly predicted major bleeding (AUC = 0.759, p  = 0.001). None of the aspirin-related assays predicted MACE. Prasugrel or ticagrelor treatment was associated with lower long-term mortality than clopidogrel (HR = 0.411; 95% CI: 0.27–0.62; p  < 0.001). Concomitant use of potent P2Y12 inhibitors and aspirin resulted in fewer aspirin semi- or non-responders and lower rates of dual HTPR. Dual HTPR occurred in ~ 1% of ticagrelor-, 2% of prasugrel-, and 7% of clopidogrel-treated patients. Exploratory analyses suggested that AA-MEA and CPA-SC were associated with long-term mortality and major bleeding, respectively. Given the modest discriminatory performance of AA-MEA, these findings require external validation. Potent P2Y12 inhibitors reduced dual HTPR, while platelet function assays provided complementary prognostic information in CAD.