Atrial Fibrillation Doubles Risk of Major Cardiac Events in Peripheral Arterial Disease

Patients with peripheral arterial disease (PAD) who also have atrial fibrillation (AFib) face significantly elevated risk for major adverse cardiovascular events, according to research presented at the American Heart Association Scientific Sessions 2025. The Intermountain Health study analyzed 7613 adult patients with first-time PAD diagnoses and found that AFib was present in approximately 1 in 4 patients with PAD, making this combination far more common than previously recognized.¹

Study Findings

Among patients with PAD who have AFib, 25% experienced a major adverse cardiovascular event (MACE) within 1 year and 46% within 3 years, compared with 12% and 25%, respectively, for those without AFib. Death and heart failure hospitalization were the greatest contributors to MACE.¹

After adjustment for baseline differences and guideline-directed medical therapy, patients with AFib were 21% more likely to have MACE and 1.4 to 1.5 times more likely to be hospitalized for heart failure compared with those without AFib. MACE included all-cause death, myocardial infarction, hospitalization for heart failure, stroke, and hospitalization for unstable angina.¹

Approximately 99% of the study population had symptomatic PAD. Peripheral arterial disease affects an estimated 8 million to 12 million US adults and develops from plaque buildup in the arteries of the extremities, usually the legs. Patients with PAD experience a higher risk of heart attacks, strokes, and amputations compared with those with coronary artery disease alone.^1,2

Clinical Implications

The findings underscore the need for screening AFib in patients with PAD and implementing aggressive preventive treatment.^1,2

“This is a stark reminder that PAD is not just a limb-threatening disease—it’s a marker of widespread atherosclerosis,” Viet Le, DMSc, MPAS, PA-C, principal investigator of the study and cardiovascular researcher at Intermountain Health, said in a news release. “When AFib is added to the mix, the risk of heart attack, stroke, and death escalates significantly.”²

Despite existing guidelines, only 35% of patients with PAD receive optimal medical therapy, including blood pressure control, statins, aspirin, and smoking cessation support. The presence of both PAD and AFib derives from plaque buildup in femoral and arterial arteries, emphasizing the systemic nature of atherosclerotic disease.¹

Pharmacist Implications

Pharmacists caring for patients with PAD should routinely screen for symptoms suggesting AFib during medication therapy management encounters. Patients reporting palpitations, irregular heartbeat, fatigue, or unexplained shortness of breath warrant referral for electrocardiographic evaluation. Many individuals with AFib remain asymptomatic, making pulse checks during blood pressure monitoring valuable for detecting irregular rhythms.

Antithrombotic management becomes particularly complex when PAD coexists with AFib. For patients with PAD and AFib, full-dose oral anticoagulation takes priority over dual pathway inhibition strategies used in PAD alone. The phase 3 COMPASS trial (NCT01776424) established that low-dose rivaroxaban (Xarelto; Johnson & Johnson) 2.5 mg twice daily plus aspirin 100 mg daily reduces major adverse cardiovascular and limb events in stable patients with PAD without AFib. However, patients requiring therapeutic anticoagulation for AFib should receive full-dose anticoagulant monotherapy without the routine addition of antiplatelet therapy.^3-6

This distinction matters because adding aspirin to full-dose direct oral anticoagulants in atrial fibrillation significantly increases bleeding risk without clear benefit in stable disease. Pharmacists should verify that patients with PAD newly diagnosed with AFib have their antithrombotic regimen appropriately adjusted from dual pathway inhibition to therapeutic anticoagulation alone, unless recent revascularization or acute coronary syndrome warrants short-term dual or triple therapy under careful monitoring.^3,4

Comprehensive cardiovascular risk reduction remains essential for this high-risk population. Pharmacists should ensure patients receive statin therapy at appropriate intensity, blood pressure medications achieving target goals, and smoking cessation support, if applicable. Given the lack of patients with PAD who receive optimal medical therapy, this represents a significant opportunity for pharmacist intervention through medication optimization and patient education.¹

REFERENCES

1. Le V, et al. Atrial fibrillation prevalence in peripheral arterial disease: a long-term analysis of major adverse cardiovascular events. Presented at: American Heart Association Scientific Sessions 2025; November 10, 2025; New Orleans, LA.

2. Patients with peripheral arterial disease who also have atrial fibrillation face significantly higher risk for cardiac events including death. News release. Intermountain Health. November 10, 2025. https://news.intermountainhealth.org/patients-with-peripheral-arterial-disease-who-also-have-atrial-fibrillation-face-significantly-higher-risk-for-cardiac-events-including-death-intermountain-study-finds/

3. McClure GR, Kaplovitch E, Narula S, Bhagirath VC, Anand SS. Rivaroxaban and aspirin in peripheral vascular disease: a review of implementation strategies and management of common clinical scenarios. Curr Cardiol Rep. 2019;21(10):115. doi:10.1007/s11886-019-1198-5

4. Bonaca MP, Barnes GD, Bauersachs R, et al. Antithrombotic strategies for patients with peripheral artery disease: JACC scientific statement. J Am Coll Cardiol. 2024;84(10):936-952. doi:10.1016/j.jacc.2024.06.027

5. Anand SS, Bosch J, Eikelboom JW, et al; COMPASS Investigators. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391(10117):219-229. doi:10.1016/S0140-6736(17)32409-1

6. Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med. 2020;382(21):1994-2004. doi:10.1056/NEJMoa2000052