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

Eur Heart J Cardiovasc Pharmacother. 2023 Apr 10;9(3):262-270. doi: 10.1093/ehjcvp/pvad008.

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.

Keywords: Acute coronary syndrome; De-escalation; Diabetes mellitus; Percutaneous coronary intervention; Prasugrel.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome* / drug therapy
  • Acute Coronary Syndrome* / therapy
  • Brain Ischemia* / etiology
  • Clopidogrel
  • Diabetes Mellitus* / drug therapy
  • Hemorrhage / chemically induced
  • Humans
  • Ischemia / drug therapy
  • Myocardial Infarction* / drug therapy
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Aggregation Inhibitors
  • Prasugrel Hydrochloride
  • Stroke* / etiology

Substances

  • Prasugrel Hydrochloride
  • Platelet Aggregation Inhibitors
  • Clopidogrel

Associated data

  • ClinicalTrials.gov/NCT02193971