Adding the antiplatelet drug ticagrelor to aspirin as long-term therapy following myocardial infarction (MI) may significantly reduce the rate of subsequent death from cardiovascular causes, MI or stroke, according to data presented at the American College of Cardiology (ACC) Scientific Sessions 2015.

Results also showed that the benefit of adding ticagrelor to aspirin appeared to accrue for nearly 3 years. 

The double-blind PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS] — Thrombolysis in Myocardial Infarction [TIMI]) included 21,162 patients with a history of MI randomly assigned to one of two ticagrelor doses or placebo.

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“Previous trials have just been 1 year in duration. We didn’t have data for extending the use of it beyond longer than that,” said study principal investigator Marc Sabatine, MD, MPH, who is the chair of the TIMI Study Group and a senior physician in the cardiovascular division at Brigham and Women’s Hospital and Harvard Medical School in Boston. “We looked at stable patients with a history of MI. Some individuals were followed up to 4 years.”      

He said the benefit with this agent was consistent across the individual components of the composite endpoint — CV death, MI or stroke — and in all the major subgroups of patients. He said the event curves continue to spread out over time, suggesting that the benefit continues to accrue over time in these patients who were followed for a median of 33 months.

Previous studies have shown a benefit by adding a second antiplatelet agent such as a P2Y12 inhibitor like ticagrelor. However, since all the studies included a follow-up of only 12 months, there were unanswered questions about the potential benefits and risks of dual antiplatelet therapy in stable patients with a history of MI.

This current study evaluated the efficacy and safety of ticagrelor plus aspirin (75 mg to 150 mg) for the prevention of major adverse CV events. Patients with a history of spontaneous MI within 1 to 3 years with at least one additional high-risk factor were randomly assigned to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily or matching placebo. All the patients received low-dose aspirin and were enrolled between October 2010 and April 2013. The mean age was 65 years and 76% were men. 

The findings from the study, which were simultaneously published online in the New England Journal of Medicine, indicated that ticagrelor reduced the chances of CV death, MI or stroke. Specifically, the researchers found a 15% reduction in the 90-mg group and a 16% reduction in the 60-mg group compared with the placebo group.

Dyspnea was more common with ticagrelor than placebo and led to discontinuation of the study drug in about 5% of patients on the drug. Bleeding led to discontinuation of ticagrelor in about 7% of patients on the study drug. 

Dr. Sabatine said efficacy was virtually identical with both ticagrelor doses, and the risks for bleeding and dyspnea tended to be as predicted, although the risks were “a bit more” with the 90-mg than the 60-mg dose. However, the trial wasn’t designed to compare the two dose levels.

AstraZeneca sponsored the trial.


  1. Sabatine M et al. Joint ACC/JACC Late-Breaking Clinical Trials. 400-18 – Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin (PEGASUS) – Thrombolysis in Myocardial Infarction (TIMI) 54. Presented at: American College of Cardiology (ACC) 64th Annual Scientific Session & Expo; March 14-16, 2015; San Diego.
  2. Bonaca MP et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1500857.