Chronic kidney disease and risk for cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: The EUCLID trial

Vasc Med. 2019 Oct;24(5):422-430. doi: 10.1177/1358863X19864172. Epub 2019 Jul 24.

Abstract

In patients with symptomatic peripheral artery disease (PAD), the impact of chronic kidney disease (CKD) on major adverse cardiovascular events has not been fully evaluated. The Examining Use of Ticagrelor In PAD (EUCLID) trial randomized 13,885 patients with PAD to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. This post hoc analysis compared the incidence of the primary composite endpoint (cardiovascular death, myocardial infarction (MI), or ischemic stroke) in patients with CKD (eGFR < 60 mL/min/1.73 m2) with those without CKD (eGFR ⩾ 60 mL/min/1.73 m2). The primary safety endpoint was thrombolysis in MI (TIMI) major bleeding. A total of 13,483 patients were included; 3332 (25%) had CKD, of whom 237 had stage 4/5 disease. Median follow-up was approximately 30 months. After statistical adjustment, patients with CKD had a higher rate of the primary endpoint compared with those without CKD (6.75 vs 3.72 events/100 patient-years; adjusted hazard ratio (HR) 1.45, 95% CI 1.30-1.63). CKD was not associated with increased risk of hospitalization for acute limb ischemia (ALI) (adjusted HR 0.96, 95% CI 0.69-1.34) or major amputation (adjusted HR 0.92, 95% CI 0.66-1.28). CKD was not associated with a significantly increased risk of major bleeding (adjusted HR 1.21, 95% CI 0.89-1.64), but minor bleeding was significantly increased (adjusted HR 1.51, 95% CI 1.07-2.15). In conclusion, patients with PAD and CKD had higher rates of cardiovascular death, MI, and ischemic stroke, but similar rates of ALI, major amputation, and TIMI major bleeding when compared with patients without CKD. ClinicalTrials.gov Identifier: NCT01732822.

Keywords: acute limb ischemia (ALI); amputation; chronic kidney disease; major adverse cardiovascular events; major adverse limb events (MALE); major bleeding; peripheral artery disease (PAD).

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amputation
  • Brain Ischemia / mortality
  • Brain Ischemia / prevention & control
  • Clopidogrel / administration & dosage*
  • Clopidogrel / adverse effects
  • Female
  • Glomerular Filtration Rate*
  • Hemorrhage / chemically induced
  • Hemorrhage / mortality
  • Humans
  • Incidence
  • Ischemia / diagnosis
  • Ischemia / drug therapy*
  • Ischemia / mortality
  • Ischemia / physiopathology
  • Kidney / physiopathology*
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / drug therapy*
  • Peripheral Arterial Disease / mortality
  • Peripheral Arterial Disease / physiopathology
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / mortality
  • Renal Insufficiency, Chronic / physiopathology*
  • Risk Assessment
  • Risk Factors
  • Stroke / mortality
  • Stroke / prevention & control
  • Ticagrelor / administration & dosage*
  • Ticagrelor / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT01732822