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Increased cardiovascular death with single antiplatelet therapy in oral anticoagulation-treated chronic coronary artery disease: meta-analysis of randomized trials

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: INTRODUCTION: The optimal antithrombotic regimen for chronic coronary artery disease (CAD) requiring long‑term anticoagulation remains uncertain. OBJECTIVES: We aimed to determine the effects of oral anticoagulation (OAC) monotherapy in comparison with OAC plus single antiplatelet therapy (OAC+SAPT) on cardiovascular mortality in chronic CAD. The secondary objective was to assess the effects of both antithrombotic approaches on major bleeding, nonfatal ischemic events, and all‑cause death. PATIENTS AND METHODS: We searched PubMed, Embase, and Cochrane CENTRAL (up to August 2025) for randomized trials comparing OAC alone vs OAC+SAPT in chronic CAD. Fixed‑effects models were used when heterogeneity was low (I² <50%); otherwise, random‑effects models were applied. Prespecified sensitivity analyses included a Bayesian meta‑analysis and trial sequential analysis (TSA). The primary outcome was cardiovascular death; secondary outcomes were all‑cause death, major bleeding, nonfatal myocardial infarction, and ischemic stroke. RESULTS: Five trials (AFIRE, AQUATIC, EPIC‑CAD, OAC‑ALONE, and PRAEDO AF; n = 4964; follow‑up range, 12-30 mo) met the eligibility criteria. Cardiovascular death occurred in 2.7% of the patients on OAC alone vs 3.8% on OAC+SAPT (hazard ratio [HR], 0.69; 95% CI, 0.5-0.96; P = 0.02). The Bayesian analysis confirmed the result (HR, 0.75; 95% credible interval, 0.61-0.93). TSA crossed the efficacy boundary, supporting firm evidence for cardiovascular mortality reduction with OAC alone. All‑cause mortality was numerically, but not significantly, lower on OAC alone (4.9% vs 6.7%; HR, 0.79; 95% CI, 0.5-1.24; P = 0.3). Major bleeding was reduced on OAC alone (3.3% vs 6.4%; HR, 0.51; 95% CI, 0.39-0.66; P <0.001). Myocardial infarction and ischemic stroke incidence did not differ significantly in the treatment arms. CONCLUSIONS: In chronic CAD requiring anticoagulation, OAC monotherapy vs OAC+SAPT reduced cardiovascular mortality and major bleeding without an excess in nonfatal thrombotic events, generally supporting OAC alone as the preferred long‑term strategy in this patient population.

Source: Polskie Archiwum Medycyny Wewnętrznej

DOI: 10.20452/pamw.17201

Authors: Eliano P. Navarese, Dean J. Kereiakes, Timothy D. Henry, Mehriban Isgender, Giuseppe Talanas, Jacek Kubica, Michael E. Farkouh, Felicita Andreotti

Institutions: Nicolaus Copernicus University, Link Campus University, Christ Hospital, Christ Hospital, Azerbaijan Medical University, University of Sassari, Sinai Health System, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic

Language: English

Topic: Antiplatelet Therapy and Cardiovascular Diseases

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W7124276127

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