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Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease
Marc P Bonaca1, Deepak L Bhatt1, Robert F Storey2
1TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, Massachusetts.
Insights
Ticagrelor significantly reduced major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD) and prior myocardial infarction (MI). This treatment offers a substantial absolute risk reduction for MACE in this high-risk population.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Clinical Trials
Background:
- Peripheral artery disease (PAD) significantly increases ischemic and bleeding risks in patients with a history of myocardial infarction (MI).
- Understanding the impact of antiplatelet therapy in this dual-risk population is crucial for optimizing patient outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of ticagrelor in patients with PAD and prior MI.
- To assess ticagrelor's effect on major cardiovascular events (MACE) and major adverse limb events (MALE).
Main Methods:
- The PEGASUS-TIMI 54 trial randomized 21,162 patients with prior MI to ticagrelor (90 mg or 60 mg twice daily) or placebo, all on aspirin.
- Patients with known PAD at baseline were analyzed for MACE and MALE outcomes.
- Follow-up data were collected to assess the incidence of cardiovascular events, limb ischemia, and bleeding.
Main Results:
- Patients with PAD (5% of cohort) exhibited substantially higher MACE rates compared to those without PAD (19.3% vs. 8.4%).
- Ticagrelor demonstrated a consistent relative risk reduction for MACE across PAD subgroups, but a greater absolute risk reduction (4.1%) in PAD patients.
- Ticagrelor significantly reduced the risk of MALE (HR: 0.65; 95% CI: 0.44-0.95; P=0.026), with a low excess bleeding risk (0.12%).
Conclusions:
- Stable patients with prior MI and concomitant PAD face elevated ischemic risk.
- Ticagrelor effectively reduces both MACE and MALE in this high-risk PAD population, offering significant absolute risk reduction.
- The 60-mg dose of ticagrelor showed particularly favorable outcomes regarding cardiovascular and all-cause mortality.
Background:
Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI).
Objectives:
This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI.
Methods:
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 MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up.
Results:
A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026).
Conclusions:
Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562).
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