Photo courtesy of AstraZeneca
ORLANDO, FL—A subanalysis of the PEGASUS-TIMI 54 trial has provided a clearer picture of the risks and benefits associated with long-term use of the antiplatelet drug ticagrelor, according to investigators.
The goals of the analysis were to evaluate the long-term efficacy of ticagrelor in patients with a history of myocardial infarction and to determine the rates of, and reasons for, discontinuing ticagrelor in these patients.
The PEGASUS-TIMI 54 trial included 21,162 patients (age 50 and older) who had experienced a heart attack in the previous 1 to 3 years. The patients were randomized to receive aspirin plus twice-daily doses of ticagrelor at 90 mg, ticagrelor at 60 mg, or placebo.
Earlier results from this study showed that both ticagrelor doses reduced the rate of the primary endpoint, which was a composite of cardiovascular death, heart attack, and stroke.
However, the rates of TIMI major bleeding and dyspnea were higher in patients who received either dose of ticagrelor than in those who received placebo. And premature discontinuation was higher in the ticagrelor arms.
To investigate this further, Marc Bonaca, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues conducted their subanalysis. The results were presented in a late-breaking clinical trials session at the American Heart Association (AHA) Scientific Sessions 2015.
The trial lasted a median of 33 months. During this time, the rate of discontinuation (of ticagrelor or placebo) was 32% in the 90 mg ticagrelor arm, 29% in the 60 mg ticagrelor arm, and 21% in the placebo arm (P<0.001).
The rates of discontinuation due to patient decision or an administrative reason were similar between the arms.
However, patients were more likely to stop taking the study drug due to an adverse event (AE) if they were receiving ticagrelor rather than placebo. Discontinuation due to an AE was 19% in the 90 mg ticagrelor arm, 16.4% in the 60 mg ticagrelor arm, and 8.9% in the placebo arm (P<0.01).
The most frequent AEs leading to discontinuation were bleeding—6.5% in the 90 mg arm, 5.1% in the 60 mg arm, and 1.2% in the placebo arm (P<0.001)—and dyspnea—6.2%, 4.3%, and 0.7%, respectively (P<0.001).
Rates of AEs leading to discontinuation were highest in the first year—16% in the 90 mg arm, 13% in the 60 mg arm, and 6% in the placebo arm.
In those patients who stayed on therapy, discontinuation rates over the subsequent 2 years were 6.5% in the 90 mg arm, 6.0% in the 60 mg arm, 4.6% in the placebo arm.
In patients who stayed on therapy, ticagrelor reduced the rate of the composite efficacy endpoint of cardiovascular death, myocardial infarction, or stroke at 3 years (hazard ratio=0.79), which is consistent with the results of the overall population of the study.
“This analysis pointed to important patterns with regards to common AEs associated with ticagrelor in the context of clinical benefit,” Dr Bonaca said.
“Physicians must consider the overall risks, including higher rates of bleeding and dyspnea, particularly within the first year. For patients at increased risk for recurrent cardiovascular events in the long-term, ticagrelor can provide an important benefit.”
PEGASUS-TIMI 54 was sponsored by AstraZeneca, the company developing ticagrelor. Investigators involved in the subanalysis reported relationships with a range of other companies as well.
