Sex-Specific Risks of Major Cardiovascular and Limb Events in Patients With Symptomatic Peripheral Artery Disease

Abstract

Background: Patients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD.

Objectives: The aim of this post hoc analysis was to evaluate sex-specific differences in MACE and limb events in the EUCLID (Examining Use of Ticagrelor in PAD) trial.

Methods: Cox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection.

Results: EUCLID enrolled 13,885 patients with PAD (28% women [n = 3,888]). PAD severity and medical treatment were comparable between sexes, whereas prior lower extremity revascularization was reported less frequently in women (54.8% vs. 57.3%; p = 0.006). Women were older (mean ± SD age: 67.8 ± 8.9 vs. 66.1 ± 8.2 years; p < 0.001) and more likely to have diabetes mellitus (p = 0.004), hypertension, hyperlipidemia, and chronic kidney disease (all p < 0.001). Over a mean follow-up of 30 months, women had a lower risk of MACE (9.5% vs. 11.2%; adjusted hazard ratio: 0.77; 95% confidence interval: 0.68 to 0.88; p < 0.001) and all-cause-mortality (7.6% vs. 9.7%; adjusted hazard ratio: 0.61; 95% confidence interval: 0.53 to 0.71; p < 0.001). In contrast, risk for major adverse limb events (2.6% vs. 3.0%) and hospitalization for acute limb ischemia (1.6% vs. 1.7%) were not different by sex.

Conclusions: Although women with PAD are at lower risk for MACE and all-cause mortality, risk for limb events was similar between sexes over a mean follow-up of 30 months. Understanding sex-specific differences and dissociation between baseline cardiovascular risk and subsequent cardiovascular events requires further investigation. (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).

Keywords: cardiovascular event; lower extremity; peripheral artery disease; revascularization; risk factor; sex.