Prasugrel dose de-escalation in diabetic patients with acute coronary syndrome receiving percutaneous coronary intervention: Results from HOST-REDUCE-POLYTECH-ACS trial

Abstract Aims The aim of this study was to evaluate the efficacy and safety of prasugrel-dose de-escalation therapy in patients with diabetes mellitus (DM)-acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Methods and results This was a post-hoc analysis of the HOST-REDUCE-POLYTECH-ACS randomized trial. The efficacy and safety of prasugrel dose de-escalation therapy (prasugrel 5 mg daily) were compared with conventional therapy (prasugrel 10 mg daily) in patients with DM. The primary endpoint was net adverse clinical events (NACE), defined as a composite of all-cause death, nonfatal myocardial infarction (MI), stent thrombosis (ST), clinically driven revascularization, stroke, and BARC class ≥ 2 bleeding events. The secondary ischemic outcome was major adverse cardiovascular and cerebrovascular events (MACE), defined as the composite of cardiac death, nonfatal MI, ST, or ischemic stroke. Of 2 338 patients randomized, 990 had DM. The primary endpoint of NACE occurred in 38 patients (7.6%) receiving prasugrel dose de-escalation and in 53 patients (11.3%) receiving conventional therapy among patients with DM (HR 0.66; 95% CI 0.43—0.99; P = 0.049). Prasugrel dose de-escalation as compared with conventional therapy did not increase the risk of ischemic events (HR 1.03; 95% CI 0.56–1.88; P = 0.927) but decreased BARC class ≥ 2 bleeding in patients with DM (HR 0.44; 95% CI 0.23–0.84; P = 0.012). Conclusion Prasugrel dose de-escalation compared with conventional therapy may reduce the risk of net clinical outcomes, mostly driven by a reduction in bleeding without an increase in ischemic events in patients with DM.