The Twilight of Aspirin: A Meta-Analysis of P2Y12 Inhibitor Monotherapy vs. Dual Antiplatelet Therapy (DAPT) Following Third-Generation Drug-Eluting Stent Implantation.

Original Research | 2026 | Volume 2 | Issue 1 | Page 01-14

Dr. Ibrahim Kureshy, Lecturer, Cardiology, DMCH-UAE

Abstract

The Twilight of Aspirin_ A Meta-Analysis of P2Y12 Inhibitor Monotherapy vs (1).pdf

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For decades, dual antiplatelet therapy (DAPT)—combining aspirin with a P2Y_{12} inhibitor—has been the gold standard for preventing thrombotic complications following percutaneous coronary intervention (PCI). However, the advent of third-generation drug-eluting stents (DES) with thinner struts and biocompatible polymers has significantly reduced stent thrombosis rates, shifting the clinical focus toward mitigating DAPT-associated bleeding. This meta-analysis evaluates whether P2Y_{12} inhibitor monotherapy is superior or non-inferior to conventional DAPT in the modern DES era.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing P2Y_{12} inhibitor monotherapy (after a short course of 1–3 months of DAPT) against standard DAPT durations (6–12 months) in patients undergoing PCI with third-generation DES. The primary safety endpoint was Major Bleeding (defined by BARC 3 or 5), and the primary ischemic endpoint was Major Adverse Cardiovascular and Cerebrovascular Events (MACCE), including myocardial infarction, stroke, and stent thrombosis.

Results

Data from 57 clinical trials involving 56 patients were synthesized. P2Y_12 inhibitor monotherapy was associated with a significant reduction in major bleeding complications compared to standard DAPT (Hazard Ratio: 0.52; 95% CI: 0.45–0.61; p < 0.001). Regarding ischemic protection, monotherapy demonstrated non-inferiority to DAPT for MACCE (HR: 1.02; 95% CI: 0.91–1.14; p = 0.68). Subgroup analyses indicated that the benefits of bleeding reduction remained consistent across high-bleeding-risk (HBR) populations and various P2Y_{12} inhibitor types (ticagrelor, clopidogrel, or prasugrel).

Conclusion

The "Twilight of Aspirin" appears supported by contemporary evidence. Following third-generation DES implantation, transitioning to P2Y_{12} inhibitor monotherapy after a brief period of DAPT significantly reduces bleeding risk without a compensatory increase in ischemic events. These findings suggest that a monotherapy strategy may be the preferred post-PCI regimen for optimizing the net clinical benefit in a broad range of patients. Keywords: P2Y_{12} inhibitor, Monotherapy, Aspirin, Dual Antiplatelet Therapy, Drug-Eluting Stents, PCI, Bleeding Risk.