Design and rationale for the Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial

Am Heart J. 2014 Apr;167(4):437-444.e5. doi: 10.1016/j.ahj.2013.12.020. Epub 2014 Jan 6.

Abstract

Background: P2Y12 receptor antagonist therapy is recommended in addition to ASA for up to 1 year after acute coronary syndrome to reduce ischemic events. In contrast, the benefit of long-term dual antiplatelet therapy beyond 1 year remains unclear. Ticagrelor is a potent, reversibly binding P2Y12 receptor-antagonist that has been shown to be superior to clopidogrel in patients with acute coronary syndromes for up to 1 year.

Study design: PEGASUS-TIMI 54 is a randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor in addition to aspirin (75-150 mg) for the prevention of major adverse cardiovascular events in patients with a history of myocardial infarction and risk factors. Patients with a history of spontaneous myocardial infarction within 1 to 3 years are randomized in a 1:1:1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or matching placebo, all with low dose ASA, until the end of the study. The primary endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. Recruitment began in October 2010 and completed in April 2013 with a sample size of over 21,000 patients. The trial is planned to continue until the latest of either 1,360 adjudicated primary end points are accrued or the last patient randomized has been followed for at least 12 months.

Conclusions: PEGASUS-TIMI 54 is investigating whether the addition of intensive antiplatelet therapy with ticagrelor to low-dose aspirin reduces major adverse cardiovascular events in high-risk patients with a history of myocardial infarction.

Trial registration: ClinicalTrials.gov NCT01225562.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Coronary Syndrome / prevention & control*
  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives*
  • Aspirin / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Fibrinolytic Agents / administration & dosage
  • Humans
  • Multicenter Studies as Topic / methods
  • Myocardial Infarction / drug therapy*
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Randomized Controlled Trials as Topic / methods*
  • Thrombolytic Therapy / methods*
  • Ticagrelor

Substances

  • Fibrinolytic Agents
  • Purinergic P2Y Receptor Antagonists
  • Ticagrelor
  • Adenosine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT01225562