Dyspnea, bleeding most common causes of ticagrelor discontinuation
ORLANDO, Fla. — The most frequent causes of ticagrelor discontinuation in the PEGASUS?TIMI 54 study were dyspnea and bleeding, and many of those events were minor, according to results of a substudy presented at the American Heart Association Scientific Sessions.
“Discontinuation of newly started ticagrelor (Brilinta, AstraZeneca) among stable outpatients with prior MI was driven by adverse events of bleeding and dyspnea,” Marc P. Bonaca, MD, MPH, investigator for the TIMI Study Group and associate physician at Brigham and Women’s Hospital and Harvard Medical School, said during a press conference. “Although significant enough to prompt discontinuation, the majority of dyspnea, more than 95%, was nonserious, and more than 80% was mild to moderate in intensity, and most bleeds were classified as minimal or needing medical attention.”
Bonaca and colleagues investigated rates, reasons and timing of ticagrelor discontinuation in patients randomized to receive this therapy in PEGASUS?TIMI 54. Overall results of the trial demonstrated that stable patients with MI 1 to 3 years prior assigned aspirin plus ticagrelor had lower rates of CV death, MI and stroke, but higher rates of bleeding compared with those assigned aspirin alone.
The discontinuation information is important because “translation of PEGASUS-TIMI 54 into clinical practice would be more likely in the form of continuing in patients already tolerating ticagrelor for 1 year after their MI,” Bonaca said here.
At 1 year, the rate of discontinuation was 6% for patients assigned placebo, 13% for those assigned ticagrelor 60 mg and 16% for those assigned ticagrelor 90 mg (P for each ticagrelor dose vs. placebo < .01). In the second and third years of the study, annualized discontinuation rates were 2.3% for placebo, 3% for ticagrelor 60 mg and 3.3% for ticagrelor 90 mg, and the composite discontinuation rates were 4.5% for placebo, 6% for ticagrelor 60 mg and 6.5% for ticagrelor 90 mg (P for each ticagrelor dose vs. placebo < .01), according to results reported by Bonaca.
The 3-year Kaplan-Meier rates for adverse events leading to discontinuation were 19% for ticagrelor 90 mg, 16.4% for ticagrelor 60 mg and 8.9% for placebo, Bonaca said. The most common reasons for discontinuation in the ticagrelor arms according to 3-year Kaplan-Meier rates were bleeding (90 mg, 7.8%; 60 mg, 6.2%; placebo, 1.5%) and dyspnea (90 mg, 6.5%; 60 mg, 4.6%; placebo, 0.8%), he said.
Median days to discontinuation for dyspnea were 8 for the 90-mg dose, 11 for the 60-mg dose and 53 for placebo (P for each ticagrelor dose vs. placebo < .01). Median days to discontinuation for bleeding were 86 for the 90-mg dose, 156 for the 60-mg dose and 344 for placebo (P for each ticagrelor dose vs. placebo < .01).
The percentages of discontinuations for dyspnea that were deemed to be nonserious cases of dyspnea were 82% in the placebo group, 85% in the 90-mg group and 88% in the 60-mg group, Bonaca said.
The vast majority of discontinuations for bleeding in the ticagrelor arms were deemed to be minimal or requiring medical attention, not rising to the level of TIMI minor or major bleeding, he said.
Eliminating patients who discontinued their study drug from analysis of CV death/MI/stroke did not change the results, as both ticagrelor doses remained statistically superior to placebo, according to Bonaca.
“Among patients who remained on therapy, discontinuation for an adverse event after 1 year was low, and ischemic risk was robustly reduced,” Bonaca said. “However, ‘non-serious’ bleeding and other adverse events still have important consequences, including discontinuation of therapy. These data underscore the need for patient counseling when initiating antithrombotic therapies in order to maximize adherence and improve outcomes.” – by Erik Swain
Reference:
Bonaca MP, et al. Late-Breaking Clinical Trials 3. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
Disclosure: PEGASUS?TIMI 54 was funded by a research grant to Brigham and Women’s Hospital from AstraZeneca. Bonaca reports consulting for AstraZeneca, Bayer, Merck and Roche Diagnostics.
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