THERAPEUTIC WINDOW FOR P2Y12-RECEPTOR INHIBITION: A COLLABORATIVE ANALYSIS OF THE RELATION BETWEEN PLATELET REACTIVITY, STENT THROMBOSIS AND BLEEDING

Abstract

background: Although residual platelet reactivity during treatment with P2Y12-inhibitors is associated with stent thrombosis (ST) and bleeding, clinically validated, standardized cut-offs for platelet function testing are lacking. We sought to determine the prognostic impact of low (LPR), optimal (OPR), or high platelet reactivity (HPR) by applying standardized cut-off criteria in patients undergoing PCI treated with clopidogrel or prasugrel. methods: Authors of studies published before January 2014, reporting the association between platelet reactivity, ST and major bleeding were contacted for a collaborative analysis using a priori defined, uniform cut-off values for standardized platelet function assays. Based on the best available evidence (exploratory studies), LPR-OPR-HPR categories were defined as 208 PRU for VerifyNow, 46U for the Multiplate analyzer and 50% for VASP assay. Results: Fifteen studies including 18,169 patients were used for the analysis. Patients with HPR had a 2.6-fold higher risk of ST (p<0.00001) but a similar risk for bleeding (p=0.053) compared to those with OPR. In contrast, patients with LPR had a 1.8-fold higher risk for bleeding (p<0.0001), but identical risk for ST (p=0.81) as those with OPR. Mortality was 1.6-fold higher in patients with HPR compared to others (p<0.001). Validation cohorts confirmed the clinical relevance of cut-off values suggested by exploratory studies. conclusion: During thienopyridine treatment, mortality and ST is significantly higher in HPR, while LPR is a predictor of bleeding. Potential benefits of targeting OPR as a therapeutic window for P2Y12-inhibition need to be confirmed in randomized trials.