Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial

Circulation. 2019 Dec 3;140(23):1865-1877. doi: 10.1161/CIRCULATIONAHA.119.041766. Epub 2019 Sep 25.

Abstract

Background: Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain.

Methods: In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months.

Results: At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% [45/400] vs 5.3% [21/400]; hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.34 to 3.79; P=0.002). The incidences of major bleeding (7.5% [29/400] vs 4.1% [16/400], P=0.04) and fatal bleeding (1% [4/400] vs 0%, P=0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% [36/400] vs 5.8% [23/400]; HR, 1.62; 95% CI, 0.96 to 2.74; P=0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups.

Conclusions: In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02094963.

Keywords: acute coronary syndrome; clopidogrel; ticagrelor.

Publication types

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

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / ethnology
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / therapy
  • Aged
  • Aged, 80 and over
  • Asian People
  • Cause of Death
  • Clopidogrel / adverse effects*
  • Clopidogrel / therapeutic use
  • Combined Modality Therapy
  • Disease Susceptibility
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Hemorrhage / mortality
  • Hospital Mortality
  • Humans
  • Male
  • Middle Aged
  • Patient Dropouts
  • Percutaneous Coronary Intervention
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Premedication
  • Purinergic P2Y Receptor Antagonists / adverse effects*
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Republic of Korea / epidemiology
  • Sample Size
  • Ticagrelor / adverse effects*
  • Ticagrelor / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT02094963