Examining Use of Ticagrelor in Peripheral Arterial Disease - EUCLID

Contribution To Literature:

The EUCLID trial failed to show that ticagrelor was superior to clopidogrel among patients with PAD.

Description:

The goal of the trial was to evaluate treatment with ticagrelor compared with clopidogrel among patients with peripheral arterial disease (PAD).

Study Design

  • Randomized
  • Parallel
  • Blinded

Patients with PAD were randomized to ticagrelor 90 mg twice daily (n = 6,930) versus clopidogrel 75 mg daily (n = 6,955).

  • Total number of enrollees: 13,885
  • Duration of follow-up: 30 months
  • Mean patient age: 66 years
  • Percentage female: 28%
  • Percentage with diabetes: 38%

Inclusion criteria:

  • Patients ≥50 years of age
  • Ankle-brachial index (ABI) ≤0.80 or prior (>30 days) revascularization of the lower extremities

Exclusion criteria:

  • Current or planned use of dual antiplatelet therapy
  • Patients determined as poor metabolizers of clopidogrel

Other salient features/characteristics:

  • Mean baseline ABI = 0.71
  • 76.6% had claudication
  • 4.6% had critical limb ischemia

Principal Findings:

The primary outcome, incidence of cardiovascular death, myocardial infarction, or ischemic stroke, occurred in 10.8% of the ticagrelor group versus 10.6% of the clopidogrel group (p = 0.65). Lack of efficacy was also observed in the cohort with a history of lower extremity revascularization: 11.4% with ticagrelor versus 11.3% with clopidogrel (p = 0.90).

Secondary outcomes:

  • Acute limb ischemia: 1.7% with ticagrelor versus 1.7% with clopidogrel
  • Major bleeding: 1.6% with ticagrelor versus 1.6% with clopidogrel
  • Dyspnea resulting in drug discontinuation: 4.8% with ticagrelor versus 0.8% with clopidogrel (p < 0.001)

Interpretation:

Among patients with symptomatic PAD, ticagrelor was not superior to clopidogrel in preventing major adverse cardiac events. Acute limb ischemia and major bleeding were also similar between treatment groups. Study drug discontinuation occurred at a higher frequency in the ticagrelor group due to dyspnea. Among patients with PAD, acceptable antiplatelet regimens include clopidogrel or aspirin monotherapy.

References:

Hiatt WR, Fowkes FG, Heizer G, et al., on behalf of the EUCLID Trial Steering Committee and Investigators. Ticagrelor versus clopidogrel in symptomatic peripheral arterial disease. N Engl J Med 2016;Nov 13:[Epub ahead of print].

Substudy: Jones WS, Baumgartner I, Hiatt WR, et al., on behalf of the International Steering Committee and Investigators of the EUCLID Trial. Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease. Circulation 2016;Nov 13:[Epub ahead of print].

Presented by Dr. Manesh R. Patel at the American Heart Association Annual Scientific Sessions (AHA 2016), New Orleans, LA, November 13, 2016.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Interventions and Vascular Medicine

Keywords: AHA Annual Scientific Sessions, Aneurysm, Ankle Brachial Index, Aspirin, Dyspnea, Hemorrhage, Intermittent Claudication, Ischemia, Lower Extremity, Myocardial Infarction, Myocardial Revascularization, Peripheral Arterial Disease, Platelet Aggregation Inhibitors, Primary Prevention, Purinergic P2Y Receptor Antagonists, Stroke, Ticlopidine, Vascular Diseases


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