Patients who have suffered a previous heart attack remain at increased risk for another myocardial infarction (MI), cardiovascular death or stroke, with no indication of the risk level waning over time. According to new research, the optimal dose of ticagrelor shows consistent benefits in reducing ischemic risk over five-plus years in heart attack patients, while its added risk for major bleeding events abates over time.

Marc P. Bonaca, MD, of the division of cardiovascular medicine at Harvard Medical School, and colleagues published these findings in the Journal of the American College of Cardiology.

“Ticagrelor reduced ischemic risk in patients with prior MI, with consistent efficacy both early and late and with a trend toward lesser excess in bleeding over time,” they wrote. “These data support consideration of prolonged therapy in patients who continue to tolerate the drug.”

A trial randomized 21,162 patients who were at least 50 years old with a spontaneous MI occurring one to three years before enrollment. Patients were placed into three treatment groups, all with a background of low-dose aspirin: ticagrelor (brand name: Brilinta) 60 mg twice daily, ticagrelor 90 mg twice daily or placebo.

The groups were then analyzed at yearly intervals for a composite of MI, cardiovascular death or stroke, and major bleeding as defined by Thrombolysis in Myocardial Infarction (TIMI) criteria. Patients were followed for a median of 33 months, and 28 percent of them were at least five years removed from their initial MI at the trial’s conclusion.

Compared to the placebo arm, patients in the 60 mg ticagrelor group demonstrated a relative risk decrease of 18 percent in the first year of the trial, 10 percent in the second year and 21 percent in the third year. TIMI major bleeding was increased by a factor of 3.2 in the first year for the ticagrelor patients, but dropped to 2.1-fold in year two and 1.7-fold in year three.

“For every 1,000 patients treated for three years, ticagrelor 60 mg twice daily would prevent 18 primary endpoint events, including six CV deaths, nine MIs and five strokes at the cost of nine TIMI major bleeds but no intracranial hemorrhages or fatal bleeding events,” the authors reported. “These data may support clinician decision making in evaluating the risk-benefit ratio of long-term ticagrelor in patients with prior MI.”

Bonaca et al. pointed out their finding regarding diminished bleeding risk over time could be biased. Because the yearly safety analyses included only patients still receiving study drugs, the patients on ticagrelor late in the trial had already demonstrated the ability to maintain the therapy without excessive bleeding.