article154

EUCLID (Ticagrelor)

"Ticagrelor versus Clopidogrel in Patients with Symptomatic Peripheral Artery Disease"

Clinical Question

Is monotherapy with ticagrelor superior to clopidogrel for preventing cardiovascular death, myocardial infarction, or ischemic stroke in patients with symptomatic peripheral artery disease?

Bottom Line

In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel in reducing cardiovascular events, and both drugs were associated with similar rates of major bleeding.

Major Points

Peripheral artery disease (PAD) is associated with an increased risk of cardiovascular events despite standard medical therapy, including antiplatelet therapy with aspirin or clopidogrel. The EUCLID trial aimed to assess whether ticagrelor, a potent antiplatelet agent, could provide better cardiovascular outcomes compared to clopidogrel in patients with PAD.

The EUCLID trial, a double-blind, event-driven trial, included 13,885 patients with symptomatic PAD who were randomized to receive either ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). After a median follow-up of 30 months, the primary efficacy endpoint—a composite of cardiovascular death, myocardial infarction, or ischemic stroke—occurred at similar rates in both groups. Major bleeding also occurred at comparable rates between the groups.

Guidelines

No guidelines have been updated to reflect the results from this trial at the time of the summary.

Design

Double-blind, event-driven, randomized, controlled trial
N=13,885 patients with symptomatic PAD
Ticagrelor (n=6,930; 90 mg twice daily)
Clopidogrel (n=6,955; 75 mg once daily)
Median follow-up: 30 months
Primary efficacy endpoint: Composite of cardiovascular death, myocardial infarction, or ischemic stroke
Primary safety endpoint: Major bleeding according to TIMI criteria

Population

Inclusion Criteria: Age ≥50 years, symptomatic PAD with ABI ≤0.80 or previous revascularization for PAD
Exclusion Criteria: Current/planned dual antiplatelet therapy or aspirin, increased bleeding risk, long-term anticoagulation, poor clopidogrel metabolizer status
Baseline Characteristics: Median age 66 years, 72% men; 43% enrolled based on ABI, 57% based on previous revascularization

Interventions

Randomized to either ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily)

Outcomes

Primary Outcomes
- Cardiovascular death, myocardial infarction, or ischemic stroke: 10.8% in ticagrelor group vs. 10.6% in clopidogrel group (HR 1.02; 95% CI, 0.92 to 1.13; P=0.65)

Secondary Outcomes
- Acute limb ischemia: Similar in both groups (1.7%; HR 1.03; 95% CI, 0.79 to 1.33; P=0.85)
- Major bleeding: Similar in both groups (1.6%; HR 1.10; 95% CI, 0.84 to 1.43; P=0.49)

Criticisms

Aspirin was not included in the trial, limiting the ability to compare the studied agents with aspirin among patients with PAD. The trial may not directly apply to all patient populations with PAD, given the unique characteristics of the cohort.

Funding

Supported by AstraZeneca.