Ticagrelor versus clopidogrel in patients with symptomatic peripheral artery disease and prior coronary artery disease: Insights from the EUCLID trial

Vasc Med. 2018 Dec;23(6):523-530. doi: 10.1177/1358863X18775594. Epub 2018 Jul 11.

Abstract

Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular morbidity and mortality. We sought to evaluate the risk of concomitant coronary artery disease (CAD) in patients with symptomatic PAD versus PAD without diagnosed CAD, and whether ticagrelor was superior to clopidogrel in reducing that risk. The EUCLID trial randomized 13,885 patients with PAD to antithrombotic monotherapy with ticagrelor or clopidogrel. CAD was defined as prior myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery. Median follow-up was 30 months. Among 4032 (29%) patients with PAD and CAD, 63% had prior MI, 54% prior PCI, and 38% prior CABG. After adjustment for baseline characteristics, patients with PAD and CAD had significantly higher rates of the primary endpoint (cardiovascular death/MI/stroke, 15.3% vs 8.9%, hazard ratio (HR) 1.50, 95% CI: 1.13-1.99; p=0.005), but no statistically significant increase in acute limb ischemia (HR 1.28, 95% CI: 0.57-2.85; p=0.55) or major bleeding (HR 1.10, 95% CI: 0.49-2.48; p=0.81) versus PAD without CAD. Among patients with PAD and CAD, there was no differential treatment effect between ticagrelor versus clopidogrel for the primary efficacy endpoint (HR 1.02, 95% CI: 0.87-1.19; p=0.84), acute limb ischemia (HR 1.03, 95% CI: 0.63-1.69; p=0.89), or major bleeding (HR 1.06, 95% CI: 0.66-1.69; p=0.81). There was a statistically significant interaction between prior coronary stent placement and study treatment ( p=0.03) with a numerical reduction in the primary efficacy endpoint with ticagrelor versus clopidogrel (13.8% vs 16.8%, HR 0.82, 95% CI: 0.65-1.03; p=0.09). Patients with PAD and prior CAD had higher composite rates of cardiovascular death, MI, and ischemic stroke versus PAD without diagnosed CAD. There were no significant differences between ticagrelor and clopidogrel in cardiovascular events or major bleeding. ClinicalTrials.gov Identifier: NCT01732822.

Keywords: acute limb ischemia; antiplatelet therapy; cardiovascular events; coronary artery disease; major bleeding; peripheral artery disease (PAD); ticagrelor.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Clopidogrel / adverse effects
  • Clopidogrel / therapeutic use*
  • Coronary Artery Bypass* / adverse effects
  • Coronary Artery Bypass* / mortality
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Double-Blind Method
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / instrumentation
  • Percutaneous Coronary Intervention* / mortality
  • Peripheral Arterial Disease / complications
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / drug therapy*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prospective Studies
  • Risk Factors
  • Stents
  • Stroke / etiology
  • Ticagrelor / adverse effects
  • Ticagrelor / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT01732822