Antiplatelet Therapy in Stable Coronary Artery Disease: A Systematic Review and Meta-Analysis.

BACKGROUND

Stable coronary artery disease (CAD) affects around 200 million people worldwide. Recent evidence with P2Y12 inhibitors, direct oral anticoagulants, and combination strategies has challenged aspirin monotherapy as the standard antithrombotic approach.

OBJECTIVES

The purpose of this study was to evaluate antiplatelet strategy efficacy and safety in stable CAD, focusing on monotherapy comparisons, oral anticoagulant strategies in atrial fibrillation with CAD, intensified therapy in high-risk patients, and diabetes-specific strategies.

METHODS

We searched databases through May 13, 2025, including randomized controlled trials (RCTs) and observational studies. Primary outcomes were major adverse cardiovascular events (MACEs) and major bleeding. We performed random-effects meta-analyses, network meta-analysis, and meta-regression.

RESULTS

Twenty-three studies (437,662 patients; 13 RCTs, 6 observational, 4 post-hoc) were included. Two RCTs (HOST-EXAM, CAPRIE; n = 24,623) demonstrated clopidogrel superiority over aspirin for MACE (hazard ratio [HR] 0.73 [0.59-0.90]) and bleeding (HR 0.63 [0.41-0.97]). In atrial fibrillation with stable CAD, 2 RCTs (AFIRE, EPIC-CAD; n = 3,276) showed anticoagulant monotherapy had superior efficacy (HR 0.61 [0.49-0.76]) and safety (HR 0.52 [0.36-0.76]) vs combination therapy; observational data (Lamberts; n = 8,700) showed discordant results. Four RCTs showed intensified therapy reduced MACE (HR 0.85 [0.80-0.91]) but increased bleeding (HR 1.85 [1.65-2.07]).

CONCLUSIONS

Based on 2 RCTs, clopidogrel monotherapy may offer advantages over aspirin in stable CAD. RCT evidence supports anticoagulant monotherapy in atrial fibrillation with stable CAD beyond 12 months post-revascularization. Intensified strategies may benefit selected high-risk patients though narrow therapeutic margins (number needed to treat 91 vs number needed to harm 85) necessitate careful patient selection.