Ticagrelor for Secondary Prevention of Peripheral Artery Disease and Myocardial Infarction

Study Questions:

What is the efficacy and safety of ticagrelor on major cardiovascular and adverse limb event rates in patients with prior myocardial infarction (MI) and peripheral artery disease (PAD)?


The PEGASUS-TIMI 54 trial randomized 21,162 patients with prior MI (1-3 years) to ticagrelor 90 mg BID, 60 mg BID, or placebo in addition to low-dose aspirin. Patients with a history of PAD at trial enrollment were included in this secondary analysis. The occurrence of major adverse cardiovascular events (MACE; defined as cardiovascular death, MI, or stroke) or major adverse limb events (MALE; defined as acute limb ischemia or peripheral revascularization for ischemia) were identified during the 3-year follow-up period.


Of the total PEGASUS-TIMI 54 study population, 1,143 (5%) patients had known PAD at baseline. In the placebo group, PAD patients (n = 404) had higher rates of MACE (19.3% vs. 8.4%, adjusted hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.20-2.13; p = 0.0013) than non-PAD patients. The relative risk reduction in MACE with ticagrelor versus placebo was consistent regardless of PAD status, but PAD patients experienced the greatest absolute risk reduction (4.1%, number needed to treat = 25) with an absolute increase in TIMI major bleeding of 0.12% (number needed to harm = 834). MALE risk was reduced with ticagrelor (HR, 0.65; 95% CI, 0.44-0.95; p = 0.026) as compared to placebo among PAD patients.


The authors concluded that stable patients with prior MI and concomitant PAD are at increased ischemic risk, and that ticagrelor appears to reduce both MACE and MALE risk.


This secondary analysis of the large PEGASUS-TIMI 54 trial highlights the substantial ischemic risk that patients with PAD experience. Although underpowered to detect acute limb ischemia prevention, the use of ticagrelor (in addition to low-dose aspirin) appears to offer MACE and MALE risk reduction over placebo with a minimal increased risk of major bleeding. Similar findings have been reported for the addition of vorapaxar (a PAR-1 antagonist) to low-dose aspirin in patients with prior MI or PAD. Clinicians should maintain a high index of suspicion for a PAD diagnosis in patients with concomitant coronary artery disease, as these patients are at highest ischemic risk for which additional antiplatelet therapy may offer benefit.

Clinical Topics: Acute Coronary Syndromes, Prevention, Vascular Medicine

Keywords: Acute Coronary Syndrome, Adenosine, Aspirin, Myocardial Infarction, Myocardial Ischemia, Peripheral Arterial Disease, Purinergic P2Y Receptor Antagonists, Risk Reduction Behavior, Secondary Prevention, Stroke, Vascular Diseases

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