The results of a subanalysis of the PEGASUS-TIMI 54 study have been presented at a late-breaking clinical trial session at the 2015 American Heart Association (AHA) Scientific Sessions. The study evaluated reasons and rates for discontinuation of AstraZeneca’s ticagrelor (Brilinta) in patients who had experienced a myocardial infarction one to three years prior to study randomisation, and the efficacy in those patients who stayed on therapy.
The pooled analysis of the results showed that in patients who stayed on therapy, ticagrelor reduced the rate of the composite efficacy endpoint of cardiovascular death, myocardial infarction, or stroke at three years, consistent with the results of the overall population of the PEGASUS study. Discontinuation resulting from an adverse event was 8.9% in the placebo arm, 19% and 16.4% in the ticagrelor 90mg and 60mg arms, respectively, and was most frequently due to bleeding and dyspnoea. Rates of adverse events leading to discontinuation were highest in the first year at 16% in the 90mg arm, 13% in the 60mg arm, and 6% in the placebo arm. In those patients who stayed on therapy, discontinuation rates over the subsequent two years were 6.5% in the 90mg arm, 6% in the 60mg arm, 4.6% in the placebo arm.
Marc Bonaca, Thrombolysis in Myocardial Infarction [TIMI] Study Group, Brigham and Women’s Hospital, Boston, USA, and lead investigator for the subanalysis study, says “This analysis pointed to important patterns with regards to common adverse events associated with ticagrelor in the context of clinical benefit. 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.”
On September 3, 2015, the FDA approved a new 60mg tablet dosage strength for ticagrelor to be used in patients with a history of myocardial infraction beyond the first year. With this expanded indication, it is now indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or a history of myocardial infarction. For at least the first 12 months following acute coronary syndrome, ticagrelor is superior to clopidogrel. The drug also reduces the rate of stent thrombosis in patients who have been stented for treatment of acute coronary syndrome.
The PEGASUS-TIMI 54 study investigated the efficacy and safety of ticagrelor at both 60mg and 90mg twice daily, plus low dose aspirin, compared to placebo plus low dose aspirin, for the long-term prevention of atherothrombotic events in patients ≥50 years of age who had suffered a myocardial infarction one to three years prior to study enrolment and had one additional risk factor for thrombotic cardiovascular events. Only the 60mg dosage strength is approved for use in patients with a history of myopcardial infarction.