Ticagrelor Compared With Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease
Background—In patients with symptomatic peripheral artery disease (PAD) with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown.
Methods—The Examining Use of tiCagreLor In paD (EUCLID) trial randomized 13,885 patients with PAD to treatment with ticagrelor 90mg twice daily or clopidogrel 75mg daily. Patients were enrolled based on an abnormal ankle-brachial index (ABI) ≤0.80 or a prior lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the prior lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety endpoint was major bleeding.
Results—Patients with a prior revascularization had a mean age of 66 years, 73% were male, and the median baseline ABI was 0.78. After adjustment for baseline characteristics, patients enrolled based on prior revascularization had similar rates of the primary composite endpoint (hazard ratio (HR) 1.10, 95% CI 0.98-1.23, p=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, p=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, p<0.001) when compared with patients enrolled based on ABI criteria. There were no differences in ticagrelor- versus clopidogrel-treated patients for the primary efficacy endpoint (11.4% vs. 11.3%; HR 1.01, 95% CI 0.88-1.15; p=0.90), all-cause mortality (9.2% vs. 9.2%; HR 0.99, 95% CI 0.86-1.15; p=0.93), acute limb ischemia (2.5% vs. 2.5%; HR 1.03, 95% CI 0.78-1.36; p=0.84), or major bleeding (1.9% vs. 1.8%; HR 1.15, 95% CI 0.83-1.59; p=0.41). The median duration of follow up was approximately 30 months.
Conclusions—After adjustment for baseline characteristics, patients enrolled based on prior revascularization for PAD had higher rates of myocardial infarction and acute limb ischemia with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ABI criterion. There were no significant differences between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events.
Clinical Trial Registration—ClinicalTrials.gov (NCT01732822)
- Received October 10, 2016.
- Revision received November 9, 2016.
- Accepted November 9, 2016.