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)?

Methods:

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.

Results:

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.

Conclusions:

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.

Perspective:

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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