Biolimus A9-eluting stents versus other limus-eluting stents in percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials

Abstract Background Drug-eluting stents (DES) using Biolimus A9 (BES) have been widely adopted, but their performance relative to other modern limus-eluting stents remains incompletely characterized in contemporary practice. Purpose To evaluate efficacy and safety of BES compared to other limus-eluting DES by conducting a comprehensive systematic review and meta-analysis across randomized controlled trials, including sensitivity, subgroup, and robustness (leave-one-out) analyses. Methods We identified 24 RCTs enrolling 28,913 patients comparing BES (BioMatrix, Nobori, BioFreedom) vs sirolimus/everolimus/zotarolimus-eluting stents. Outcomes at 12, 24, 36, 60 months were extracted. Primary analyses used Mantel–Haenszel random-effects (DerSimonian–Laird) model. Sensitivity analyses excluded polymer-free devices and short DAPT, exclusion of 3rd-generation comparators, and STEMI-only trials. Subgroup analyses contrasted polymer-free vs biodegradable BES and 3rd vs older generation DES. Leave-one-out analysis was performed on cardiac mortality at 24 months to assess influence of individual trials. Results At 12 months, BES were associated with increased MI (RR 1.16 95% CI 1.01–1.33, I² = 10%), TLR (RR 1.26 95% CI 1.04–1.53, I² = 37%), and TVR (RR 1.14 95% CI 1.01–1.28, I² = 0%), with no significant difference in cardiac mortality or stent thrombosis. At 24 months, BES conferred reduced cardiac mortality (RR 0.81 95% CI 0.66–0.98), but this significance attenuated at longer follow-up. Sensitivity analyses upheld primary findings, though exclusion of comparators of 3rd generation attenuated significance. RIsk of bias was evaluated with Cochrane RoB-2 tool. Publication bias was investigated through visual inspection of funnel plots and the Egger's regression test. Subgroup analysis showed polymer-free BES had highest relative risk (e.g. TLR: RR 1.88 95% CI 1.09–3.26). Leave-one-out revealed that removal of LEADERS, ONYX ONE or SORT-OUT IX weakened mortality benefit, while exclusion of smaller trials did not materially alter the effect. Conclusions In this comprehensive meta-analysis, BES demonstrated a consistent safety profile but lower efficacy compared to contemporary DES, particularly at 1 year. The intermediate-term cardiac mortality benefit is driven by few influential trials and not sustained long-term. Differences are most marked versus polymer-free BES and when compared with 3rd-generation DES. These findings suggest that Biolimus-eluting platforms may no longer be optimal first-choice in the current era of ultrathin, bioabsorbable polymer DES.12 months TLR and TVRFor image description, please refer to the figure legend and surrounding text. 12 months MI and 24 months cardiac deathFor image description, please refer to the figure legend and surrounding text.