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Predictors, Type, and Impact of Bleeding on the Net Clinical Benefit of Long-Term Ticagrelor in Stable Patients With
Giulia Magnani1, Diego Ardissino1, KyungAh Im2
1Parma University Hospital Parma Italy.
Insights
Ticagrelor 60 mg increases bleeding risk in prior heart attack patients, mainly from spontaneous gastrointestinal bleeds. Patients without a history of bleeding or anemia benefit most, showing reduced mortality with ticagrelor.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Ticagrelor is effective in reducing ischemic events post-myocardial infarction (MI).
- However, ticagrelor use is associated with an increased risk of bleeding.
- Identifying patients at lower bleeding risk is crucial for optimizing ticagrelor therapy in post-MI individuals.
Purpose of the Study:
- To identify predictors of bleeding risk in patients with prior MI treated with ticagrelor.
- To evaluate the net clinical benefit of ticagrelor 60 mg in patients stratified by bleeding risk.
- To analyze the characteristics and causes of bleeding events associated with ticagrelor.
Main Methods:
- The PEGASUS-TIMI 54 trial randomized 21,162 patients with prior MI to ticagrelor (60 mg or 90 mg twice daily) or placebo.
- This analysis focused on TIMI major or minor bleeding as the primary endpoint.
- Independent predictors of bleeding were identified, and patients were stratified based on the presence of a history of spontaneous bleeding or anemia.
Main Results:
- Ticagrelor 60 mg increased major or minor bleeding by 2.0% over placebo (3.4% vs. 1.4%) at 3 years, primarily due to spontaneous gastrointestinal bleeds.
- A history of spontaneous bleeding requiring hospitalization and anemia were independent predictors of bleeding.
- Patients with neither risk predictor had significantly lower bleeding rates and a more favorable benefit profile, including reduced mortality, with ticagrelor 60 mg compared to placebo.
Conclusions:
- Bleeding associated with ticagrelor 60 mg in post-MI patients is largely spontaneous gastrointestinal bleeding.
- A history of hospitalization for spontaneous bleeding or anemia identifies patients at higher bleeding risk.
- Patients without these risk factors are likely to experience a more favorable net benefit from ticagrelor 60 mg therapy.
Abstract:
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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