Key result
In patients with prior myocardial infarction, ticagrelor 60 mg twice daily increased TIMI major or minor bleeding compared to placebo at 3 years (3.4% vs 1.4%).
Why the study?
Ticagrelor reduces ischemic risk but increases bleeding after prior myocardial infarction, making identification of patients at lower bleeding risk important to optimize the risk-benefit balance.
Does ticagrelor increase TIMI major or minor bleeding in patients with prior myocardial infarction?
RCT (n=21,162)
1:1:1
Does ticagrelor increase TIMI major or minor bleeding in patients with prior myocardial infarction?
In patients with prior MI, ticagrelor 60 mg twice daily increases spontaneous GI bleeding, but patients without a history of spontaneous bleeding or anemia derive a favorable net clinical benefit including lower mortality.
May aid bleeding risk stratification for ticagrelor post-MI; hypothesis-generating for net benefit, needs prospective validation.
Background Ticagrelor reduces ischemic risk but increases bleeding in patients with prior myocardial infarction. Identification of patients at lower bleeding risk is important in selecting patients who are likely to derive more favorable outcomes versus risk from this strategy. Methods and Results PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis in Myocardial Infarction 54) randomized 21 162 patients with prior myocardial infarction in a 1:1:1 fashion to ticagrelor 60 mg or 90 mg twice daily or placebo, with ticagrelor 60 mg approved for long‐term use. TIMI major or minor bleeding was the primary end point for this analysis. Causes of bleeding were categorized by site and etiology, and independent predictors were identified. At 3 years, ticagrelor 60 mg increased the rate of TIMI major or minor bleeding by 2.0% versus placebo (1.4% placebo versus 3.4% ticagrelor). The bleeding excess was driven primarily by spontaneous gastrointestinal bleeds. A history of spontaneous bleeding requiring hospitalization and the presence of anemia were independent predictors of bleeding but not of ischemic risk. Patients with at least 1 risk predictor had 3‐fold higher rates of bleeding with ticagrelor 60 mg versus those who had neither (absolute risk increase, 4.4% versus 1.5%; P =0.01). Patients with neither predictor had a more favorable benefit profile with ticagrelor 60 mg versus placebo including lower mortality (hazard ratio, 0.79; 95% CI, 0.65–0.96; P interaction = 0.03). Conclusions In patients with prior myocardial infarction, bleeding with ticagrelor 60 mg twice daily is predominantly spontaneous gastrointestinal. A history of spontaneous bleeding requiring hospitalization or the presence of anemia identifies patients at higher risk of bleeding, and the absence of either identifies patients likely to have a more favorable net benefit with ticagrelor. Registration URL https://www.clinicaltrials.gov/ . Unique identifier: NCT01225562.
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Magnani et al. (2021) conducted an RCT in prior myocardial infarction (n=21,162). Ticagrelor vs. Placebo was evaluated on TIMI major or minor bleeding. In patients with prior myocardial infarction, ticagrelor 60 mg twice daily increased TIMI major or minor bleeding compared to placebo at 3 years (3.4% vs 1.4%).
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