Photo courtesy of AstraZeneca
SAN DIEGO—New research suggests that adding the antiplatelet drug ticagrelor to aspirin as long-term therapy after a heart attack can significantly reduce the risk of cardiovascular death, heart attack, or stroke, but it can also increase the risk of major bleeding.
Marc S. Sabatine, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, presented these results at the American College of Cardiology’s 64th Annual Scientific Session (abstract 400-18). The findings were published in NEJM as well.
The research was sponsored by AstraZeneca, the company developing ticagrelor.
The trial, known as PEGASUS-TIMI 54, included 21,162 patients who had experienced a heart attack in the previous 1 to 3 years. Each had another factor, such as age or diabetes, that put them at risk for a second heart attack.
The patients were randomized to receive aspirin plus twice-daily doses of ticagrelor at 90 mg, ticagrelor at 60 mg, or placebo.
The twice-daily 90 mg dose of ticagrelor is already approved for patients with acute coronary syndrome. The researchers included a lower dose in this study to investigate whether platelet inhibition needed 2 years after a heart attack might be different from what is needed 2 hours after a heart attack.
The team found that both ticagrelor doses reduced the rate of the primary endpoint, which was a composite of cardiovascular death, heart attack, and stroke. At 3 years, the rate was 7.85% in the 90 mg group, 7.77% in the 60 mg group, and 9.04% in the placebo group (P=0.008 for 90 mg vs placebo and P=0.004 for 60 mg vs placebo).
“The benefit we saw was remarkably consistent across the individual components of the endpoint and in all the major subgroups of patients,” Dr Sabatine said. “Moreover, we followed patients for an average of just under 3 years, and our event curves continue to spread out over time, suggesting that the benefit continues to accrue over time.”
“Efficacy was virtually identical with both ticagrelor doses,” he added. “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.”
The rates of TIMI major bleeding were 2.60% in the 90 mg group, 2.30% in the 60 mg group, and 1.06% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).
The rates of dyspnea were 18.93% in the 90 mg group, 15.84% in 60 mg group, and 6.38% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).
The rates of dyspnea leading to treatment discontinuation were 6.5% in the 90 mg group, 4.55% in the 60 mg group, and 0.79% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).
Although the differences in dyspnea and TIMI major bleeding between the 2 ticagrelor dose groups were not statistically significant, Dr Sabatine and his colleagues said the 60 mg dose may offer a more attractive benefit-risk profile.
“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,” Dr Sabatine concluded.
