Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54

Eur Heart J Cardiovasc Pharmacother. 2019 Oct 1;5(4):200-206. doi: 10.1093/ehjcvp/pvz020.

Abstract

Aims: In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.

Methods and results: Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58).

Conclusion: In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population.

Clinical trial registration: http://www.clinicaltrials.gov NCT01225562.

Keywords: Coronary artery disease; Dual antiplatelet treatment; Post-myocardial infarction.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / administration & dosage
  • Drug Approval
  • Drug Labeling
  • Drug Therapy, Combination
  • Europe
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / mortality
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Purinergic P2Y Receptor Antagonists / administration & dosage*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Ticagrelor / administration & dosage*
  • Ticagrelor / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01225562