PEGASUS-TIMI 54 Trial Shows Benefit of Long-Term Ticagrelor After MI

March 14, 2015—Findings from the PEGASUS-TIMI 54 trial demonstrated that adding the antiplatelet drug ticagrelor to aspirin as long-term therapy after a myocardial infarction (MI) significantly reduced the rate of subsequent death from cardiovascular causes, MI, or stroke, with the benefit appearing to accrue for approximately 3 years.

Principal investigator Marc S. Sabatine, MD, presented the PEGASUS-TIMI 54 study at the American College of Cardiology’s 64^th annual scientific session in San Diego, California. The study was simultaneously published online in The New England Journal of Medicine.

The 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) 54,” was sponsored by AstraZeneca, which manufactures ticagrelor and markets the drug as Brilinta in the United States. Brilinta 90 mg is indicated to reduce the rate of thrombotic CVS events in patients with acute coronary syndrome (ACS; unstable angina, or non–ST-elevation MI, ST-elevation MI).  In January 2015, AstraZeneca announced that PEGASUS-TIMI 54 had met its primary endpoint.

According to the ACC press release, the double-blind PEGASUS-TIMI 54 trial recruited 21,162 patients who had an MI in the previous 1 to 3 years. The patients were enrolled at 1,144 sites in 31 countries. Each patient had an additional factor, such as age or diabetes, that put the patient at risk for a second MI.

In the study, patients were randomly assigned to a twice-daily regimen of ticagrelor at 90 mg, ticagrelor at 60 mg, or placebo. The investigators found that both ticagrelor doses reduced the chances of cardiovascular death, MI, or stroke—the study’s primary endpoint—with a 15% reduction in the 90-mg group and a 16% reduction in the 60-mg group compared to the placebo group.

In the ACC announcement, Dr. Sabatine commented, “The benefit we saw was remarkably consistent across the individual components of the endpoint and in all the major subgroups of patients. 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.”

As noted by the ACC, previous studies have shown a benefit in adding a second antiplatelet drug like ticagrelor, from a class called P2Y12 inhibitors, but those studies investigated the additional therapy for only 1 year, leaving unanswered the question of whether patients would benefit from continuing this treatment longer.

In addition to the 90-mg dose of ticagrelor, which is approved twice-daily for patients with ACS, the study investigators included the 60-mg dose to evaluate whether platelet inhibition needed 2 years after an MI might be different from what is needed 2 hours after an MI. Findings from a pharmacokinetic and pharmacodynamic substudy comparing the two dose levels will be presented at a later date.

Dr. Sabatine noted that with blood thinners such as ticagrelor, bleeding is the major side effect, and excess bleeding was seen in both treatment arms, although bleeding into the brain and fatal bleeding were not more common with ticagrelor. Dyspnea was more common with ticagrelor than placebo. Bleeding led to discontinuation of ticagrelor in approximately 7% of patients on the study drug, and dyspnea led to discontinuation of the study drug in about 5% of patients on the drug.

He added, “Efficacy was virtually identical with both ticagrelor doses. 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,” concluded Dr. Sabatine in the ACC press release.