Prasugrel dose de-escalation in diabetic patients with acute coronary syndrome receiving percutaneous coronary intervention: results from the 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 (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases—Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) 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, non-fatal myocardial infarction (MI), stent thrombosis (ST), clinically driven revascularization, stroke, and Bleeding Academic Research Consortium (BARC) class ≥2 bleeding events. The secondary ischaemic outcome was major adverse cardiovascular and cerebrovascular events, defined as the composite of cardiac death, non-fatal MI, ST, or ischaemic stroke. Of 2338 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 [hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.43–0.99; P = 0.049]. Prasugrel dose de-escalation as compared with conventional therapy did not increase the risk of ischaemic 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 ischaemic events in patients with DM.

Trial Registration: HOST-REDUCE-POLYTECH-ACS, NCT02193971, https://clinicaltrials.gov/ct2/show/NCT02193971