ACC Report 2015: Long-term Ticagrelor protective against post-heart attack events for beyond one year

by Bruce Sylvester: The addition of antiplatelet drug ticagrelor to aspirin for long-term post-heart attack therapy has reduced  the rate of mortality from subsequent cardiovascular causes, heart attack or stroke. And this prophylactic  benefit was maintained for nearly three years, researchers reported on March 14, 2015 at the American College of Cardiology’s 64th Annual Scientific Session.

Investigators in the PEGASUS-TIMI 54 trial enrolled 21,162 subjects who had had a heart attack in the previous one to three years. Each subject had age or diabetes as a risk factor for a second heart attack. The subjects were from 31 countries, and they were randomized to a twice-daily regimen of ticagrelor at 90 mg, ticagrelor at 60 mg or placebo.

The researchers reported that both ticagrelor doses reduced the rate of cardiovascular death, heart attack or stroke, with a 15 percent reduction in the 90-mg group and a 16 percent reduction in the 60-mg group, compared to the placebo group.

“The benefit we saw was remarkably consistent across the individual components of the endpoint and in all the major subgroups of patients,” said Marc Sabatine, M.D., M.P.H., lead investigator and a senior physician in the Cardiovascular Division at Brigham and Women’s Hospital and Harvard Medical School in Boston. “Moreover, we followed patients for an average of just under three years, and our event curves continue to spread out over time, suggesting that the benefit continues to accrue over time.”

Current standard of care after a heart attack calls for patients to receive  lifetime daily aspirin to prevent clotting. Prior studies have suggested a benefit in adding a second antiplatelet drug like ticagrelor, from a class called P2Y12 inhibitors, but the additional therapy has only been studied for up to a year.

Twice-daily 90-mg  ticagrelor is already FDA-already approved for treating acute coronary syndrome. The PEGASUS team added a lower dose cohort in this study, to determine if  the platelet inhibition required two years after a heart attack might differ from inhibition required two hours after a heart attack.

“Efficacy was virtually identical with both ticagrelor doses,” Sabatine said. “Risk of bleeding and dyspnea tended to be, as predicted, a bit more with the 90-mg than the 60-mg dose, but the trial wasn’t designed to compare those two dose levels….Now that we have the evidence, when faced with a patient who has had a heart attack, based on these data, I would continue treatment with ticagrelor as long as the patient tolerated it,” Sabatine added.

AstraZeneca sponsored the trial and provided a grant to Brigham and Women’s Hospital.

This study was also published online in the New England Journal of Medicine at the time of the oral  presentation at the meeting.