Evidence-Based Diabetes Management May 2015
PEGASUS Trial Shows Long-Term Benefits of Ticagrelor After Heart Attack
Patients who took ticagrelor with aspirin for an extended period after suffering a heart attack were less likely to die later from cardiovascular causes, heart attack, or stroke, according to results presented March 14, 2015, at the 64th Annual Scien-tific Session of the American College of Cardiology, held in San Diego, California.
The results, simultaneously published in the New England Journal of Medicine, were reported from the PEGASUS-TIMI 54 trial, which involved 21,162 patients at more than 1000 sites in 31 countries. All had experienced a heart attack in the previous 1 to 3 years and had at least 1 other factor, such as diabetes or advanced age, that put them at risk of a second heart attack.
The trial’s full name is 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. Patients in the trial were randomly assigned a twice-daily regimen of ticagrelor at 90 mg or 60 mg or placebo, in addition to low-dose aspirin. Efficacy was virtually the same with both doses, according to Marc S. Sabatine, MD, MPH, senior physician in the Cardiovascular Division at Brigham and Women’s Hospital and Harvard Medical School, Boston. Sabatine presented the results at the late-breaking session and afterward at a press conference.
Ticagrelor is a dual antiplatelet therapy currently prescribed for patients with acute coronary syndrome. Sabatine said that in tracking the number of cardiovascular events that patients experienced, the “event curves” between patients taking the drug with aspirin and those taking aspirin alone continued to widen each month up to the 1-year mark, suggesting that there might be a continued benefit after that point. The question, however, was whether the dose patients needed 2 hours after a heart attack would still be needed 2 years after a heart attack. “That was the basis for our trial,” he said.
The patients’ mean age was 65 years, and 76% were male. The average time since patients had suffered a qualifying heart attack was 1.7 years. Results showed that both doses of ticagrelor reduced the likelihood of cardiovascular death, heart attack, or stroke, which was the study’s primary end point. There was a 15% reduction among those who had the 90 mg dose and a 16% reduction for those receiving the 60 mg dose, compared with those receiving placebo. Patients were followed for an average of 33 months.
“The benefit we saw was remarkably consistent across the individual components of the end point and in all the major subgroups of patients,” Sabatine said.
Many questions arose about ticagrelor’s effect on bleeding. In the data and in re-marks at the press conference, Sabatine drew distinctions between fatal events or intracranial hemorrhage and less serious events, including those that might require hospitalization. Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%), with P <.0001 for each dose vs placebo. For rates of intracranial hemorrhage or fatal bleeding, however, rates for all 3 groups were about the same: 0.63% for the 90mg dose, 0.71% for 60 mg, and 0.60% for placebo.
While taking questions during the late-breaking session, Sabatine suggested that while a 90mg dose of ticagrelor is called for immediately after a heart attack, dropping down to a 60 mg dose at the 1 year mark may make sense, due to the findings about efficacy, bleeding, and side effects.
Patients taking the drug also experienced more shortness of breath. About 7% of patients discontinued the drug due to bleeding and about 5% stopped taking it due to shortness of breath.
Valentin Fuster, MD, PhD, of Mount Sinai Hospital and editor of the Journal of the American College of Cardiology, commented that the ticagrelor results are part of “an evolving trend of using long-term dual antiplatelet therapy.” The benefits seen must be weighed against the instances of bleeding and shortness of breath, Fuster said, adding that each physician must use his or her own judg-ment given the profile of the individual patient. “I think we should be a little bit cautious,” he said.
Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction [published online March 14, 2015]. N Engl J Med. doi:10.1056/MEJMoa500857.4.