Indobufen-based dual antiplatelet therapy after percutaneous coronary intervention: A systematic review and network meta-analysis

Abstract

Objective Indobufen has been proposed as an aspirin substitute within dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), but has been compared only with aspirin plus clopidogrel. We aimed to estimate the comparative safety and efficacy of indobufen-based DAPT against contemporary antiplatelet strategies after PCI. Methods In a systematic review and frequentist random-effects network meta-analysis, we searched PubMed/MEDLINE, Embase, and CENTRAL from inception to May 2026 for randomised controlled trials of adults undergoing PCI with drug-eluting stents that compared antiplatelet strategies mapping onto seven pre-specified nodes, with aspirin plus clopidogrel as the reference. Crude per-arm event counts were extracted in duplicate. The connected primary safety outcome was major bleeding (Bleeding Academic Research Consortium [BARC] type 3/5); efficacy outcomes (myocardial infarction, stent thrombosis, all-cause death, stroke) were analysed per component. Odds ratios (ORs) with 95% confidence intervals (CIs) and P-scores were estimated. Results Eleven trials enrolling more than 55, 000 patients were included. Indobufen plus clopidogrel did not differ significantly from aspirin plus clopidogrel for major bleeding (OR 1.05, 95% CI 0.62–1.78), myocardial infarction (0.91, 0.29–2.89), stent thrombosis (1.27, 0.34–4.74), or stroke (0.96, 0.27–3.44). In a disconnected direct comparison, indobufen reduced BARC 2–5 bleeding (OR 0.62, 0.45–0.84). The significant between-strategy differences concerned others: aspirin plus ticagrelor showed higher major bleeding (2.07, 1.46–2.94) and clopidogrel monotherapy lower (0.38, 0.22–0.64). Every comparison across clusters depended on a single bridging trial, and no network contained closed loops, precluding assessment of inconsistency. Conclusions Indobufen-based DAPT was comparable, not superior, to aspirin plus clopidogrel across bleeding and ischaemic outcomes, with no signal of increased ischaemic risk. Because only one randomised trial has directly tested indobufen and all comparisons with ticagrelor-based or monotherapy strategies rest on a single bridging trial, the findings primarily support indobufen as a reasonable aspirin-sparing alternative within clopidogrel-based DAPT. Its relative position against other contemporary bleeding-reduction strategies remains unproven. These results reinforce the need for individualised antiplatelet therapy guided by patient-specific ischaemic and bleeding risk. INPLASY registration number: INPLASY202680037.