PEGASUS-TIMI 54: What is the Long-Term Tolerability of Ticagrelor?

Discontinuation of ticagrelor among patients with a prior history of myocardial infarction (MI) was mostly caused by adverse events of bleeding and dyspnea, and for patients who remained on therapy, discontinuation after one year was low and ischemic risk was "robustly reduced," according to the results of a PEGASUS-TIMI 54 trial analysis presented Nov. 10 during AHA 2015 in Orlando.

The analysis of the PEGASUS-TIMI 54 trial looked at the 21,162 patients with a history of myocardial infarction (MI) who were randomly assigned to a twice-daily regimen of ticagrelor at 90 mg, ticagrelor at 60 mg or placebo. All patients had additional risk factors such as age or diabetes, and had experienced their myocardial infarction one to three years prior to participating in the study. The analysis further examined outcomes of the 15,214 patients who remained on the treatment.

Results showed that over the course of the trial period – a mean follow-up of 33 months – more patients stopped ticagrelor at 90 mg (3.3 percent) and ticagrelor at 60 mg (3.0 percent) than placebo (2.3 percent). Adverse events were reported as the reason for discontinuation in 19 percent of those taking 90 mg of ticagrelor and 16.4 percent of those take 60 mg.

The majority of discontinuation due to dyspnea was non-serious (>95 percent) and only mild to moderate in intensity (>80 percent), while the majority of discontinuation due to bleeding was minimal or required medical attention. Overall, for the ticagrelor groups, the risk of cardiovascular death, myocardial infarction or stroke was "significantly reduced" as compared to placebo (6.7 vs. 8.4, respectively).

The investigators conclude that "blood thinning medications may be difficult to tolerate in stable outpatients and that most people that stop the treatment do so for minor adverse events." Moving forward, they note that their results "underscore the need for patient counseling when initiating anti-thrombotic therapies in order to maximize adherence and improve outcomes."

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies

Keywords: Adenosine, Diabetes Mellitus, Lipoatrophic, Dyspnea, Hemorrhage, Myocardial Infarction, Outpatients, Stroke

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