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

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.

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.

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.

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.

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 TVR