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Efficacy and Safety of Ticagrelor Over Time in Patients With Prior MI in PEGASUS-TIMI 54
Marc P Bonaca1, Robert F Storey2, Pierre Theroux3
1TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Insights
Patients with a history of myocardial infarction (MI) face persistent high risks for cardiovascular events. Low-dose ticagrelor demonstrated consistent efficacy over time, with a trend toward reduced bleeding risks in the PEGASUS trial.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Ticagrelor is established for reducing ischemic risk post-myocardial infarction (MI).
- Long-term consistency of ischemic risk and P2Y12 inhibition benefits after MI requires further investigation.
Purpose of the Study:
- To analyze the temporal pattern of ischemic risk in patients with prior MI.
- To evaluate the consistency of ticagrelor's efficacy and safety at different time points post-randomization.
Main Methods:
- The PEGASUS-TIMI 54 trial randomized 21,162 patients with prior MI to ticagrelor (90 mg or 60 mg) or placebo, all on aspirin.
- Cardiovascular death, MI, stroke, and major bleeding rates were assessed at annual intervals (years 1, 2, 3).
Main Results:
- Ischemic risk (CV death, MI, stroke) remained constant at ~3% annually in the placebo group.
- Ticagrelor 60 mg showed consistent efficacy across all landmarks (Year 1 HR: 0.82; Year 2 HR: 0.90; Year 3 HR: 0.79).
- Major bleeding increased with ticagrelor 60 mg, with the highest hazard observed in the first year (Year 1 HR: 3.22).
Conclusions:
- Patients with prior MI exhibit sustained high risk for cardiovascular events up to 5 years post-MI.
- Low-dose ticagrelor maintains consistent efficacy over time.
- A trend towards decreased excess bleeding was observed with prolonged ticagrelor use.
Background:
Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time.
Objectives:
The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization.
Methods:
The PEGASUS-TIMI (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 trial randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3).
Results:
A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65).
Conclusions:
Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).
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