Risk for MACE, Mortality, but Not MALE, Found to Be Lower in Women vs Men With PAD

peripheral artery disease, feet, PAD
The risk for major adverse cardiovascular events and all-cause mortality was found to be lower in women vs men with symptomatic stable lower extremity peripheral artery disease.

The risk for major adverse cardiovascular events (MACE) and all-cause mortality was found to be lower in women vs men with symptomatic stable lower extremity peripheral artery disease (PAD), according to a study published in the Journal of the American College of Cardiology.

Patients with vs without PAD are known to be at a greater risk for MACE, but sex differences for cardiovascular (CV) and limb outcomes in this population are less well defined.

This was a post hoc analysis of the Examining Use of Ticagrelor in PAD trial (ClinicalTrials.gov ID NCT01732822), a multicenter,  international, double-blind prospective study in which 13,885 patients with PAD (mean age, 66.6±8.4 years; age ≥50 years) with lower extremity symptoms were treated with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily In this cohort, 3888 were women (28.0%; mean age, 67.8±8.9 years) and 9997 were men (72.0%; mean age, 66.1±8.2 years). CV outcomes examined were MACE (ie, myocardial infarction, ischemic stroke, or CV death), major adverse limb events (MALE) (ie, acute limb ischemia or major amputation), and all-cause mortality. All endpoints were adjudicated by assessors blinded to treatment group.

The severity of and medical treatment for PAD were comparable between sexes, but women underwent lower extremity revascularization (LER) procedures less often than men (54.8% vs 57.3%, respectively; P =.006). At baseline, women participants were older compared with men (mean age: 67.8±8.9 years vs 66.1±8.2 years, respectively; P <.001) and more likely to have comorbid hyperlipidemia, hypertension, and chronic kidney disease (P <.001 for all), as well as diabetes mellitus (P =.004).

During the follow-up period (mean, 30 months), women had lower risks for MACE (9.5% vs 11.2%, respectively; adjusted hazard ratio [aHR], 0.77; 95% CI, 0.68-0.88; P <.001) all-cause mortality (7.6% vs 9.7%, respectively; aHR, 0.61; 95% CI, 0.53-0.71; P <.001), MI (4.5% vs 5.1%, respectively; aHR, 0.79; 95% CI, 0.66-0.95; P <.014), and CV death (4.3% vs 5.4%, respectively; aHR, 0.65; 95% CI, 0.54-0.78; P <.001) compared with men. The risks were comparable in women and men for: MALE (2.6% vs 3.0%, respectively; aHR, 0.90; 95% CI, 0.71-1.14; P =.369), acute limb ischemia requiring hospitalization (1.6% vs 1.7%, respectively; aHR, 0.90; 95% CI, 0.66-1.24; P =.536), ischemic stroke (2.0% vs 2.2%, respectively; aHR, 0.88; 95% CI, 0.67-1.16; P =.351), and post-randomization LER (12.6% vs 12.5%, respectively; aHR, 1.02; 95% CI, 0.90-1.14; P =.797).

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Study strengths include comparable PAD severity and therapy between sexes and an excellent retention rate.

Study limitations include possible residual confounders and selection bias, non-matching of groups for all modifiable risk factors, lack of information on cumulative smoking impact, and the fact that EUCLID was not originally designed to assess sex differences.

“Sex is a key variable influencing translation of basic research to clinical trials to inform clinical practice in cardiovascular medicine, and equal inclusion of both sexes is needed to improve understanding of sex-specific differences in clinical outcomes,” noted the authors.

Disclosures:The EUCLID trial was funded by AstraZeneca.

Please see original article for conflict of interest information.


Haine A, Kavanagh S, Berger JS, et al. Sex-specific risks of major cardiovascular and limb events in patients with symptomatic peripheral artery disease. J Am Coll Cardiol. 2020;75(6):608-617. doi:10.1016/j.jacc.2019.11.057