Drug-eluting stents (DES) with controlled release of anti-proliferative drugs from durable polymer surface coatings reduce the risk of repeat revascularisation compared with use of bare-metal stents (BMS). However, early generation, durable polymer DES are associated with an increased risk of very late (>1 year) stent thrombosis (ST) compared with BMS. This has raised concerns about the long-term safety of DES. It has been postulated that the persistence of durable polymer material on the stent surface after completion of drug release is a potential trigger for chronic inflammatory responses that lead to very late ST. Biodegradable polymer drug-eluting stents aim to overcome this limitation by providing controlled drug release with subsequent degradation of the polymer material, thus removing the inflammatory stimulus. Biolimus-eluting stents (BES) were designed with a biodegradable polymer applied to the stent’s abluminal surface, which is metabolised to water and carbon dioxide within 6 to 9 months. Biolimus is a highly lipophilic sirolimus analogue and inhibits proliferation of smooth muscle cells with similar potency to sirolimus.

The LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial was a multicentre, assessor-masked, non-inferiority trial, conducted in 1707 patients with coronary artery disease (2472 lesions). They were randomised to receive either BES (n= 857, 1257 lesions) or durable polymer sirolimus-eluting stents (SES) [n= 850, 1215 lesions). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR). Both stents showed similar safety and effectiveness of BES vs. SES at 9 months. As the potential for improved safety of biodegradable polymer DES is expected to emerge only during the late phase after stent implantation, the clinical outcomes during long-term (4 years) follow-up were evaluated, focussing on the differential effects between the first year and subsequent years and the effect of ST on clinical outcomes.

The following findings were reported at 4 years (intention to treat analysis):

• Biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18.7%) patients vs. 192 (22.6%) patients (rate ratios [RR] 0.81, 95% CI 0.66 to 1.00, p <0.0001 for non-inferiority, p=0.050 for superiority).

• The RR of definite ST was 0.62 (0.35 to 1.08, p=0.09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0.20, 95% CI 0.06 to 0.67, p=0.004).

• Conversely, the RR of definite ST during the first year was 0.99 (0.51 to 1.95; p=0.98) and the test for interaction between RR of definite ST and time was positive (p =0.017 for interaction).

• An interaction with time for events associated with ST was recorded but not for other events.

• For primary endpoint events associated with ST, the RR was 0.86 (0.41 to 1.80) during the first year and 0•.7 (0.04 to 0.78) during subsequent years (p for interaction = 0.049).

The researchers conclude from these findings that “biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES.”

According to an accompanying Comment article, the existing data are not sufficient to claim superiority of biodegradable polymer DES over even first-generation DES; and LEADERS was not designed as a superiority trial, whilst the differences in major adverse clinical events recorded in the long-term follow-up, although statistically significant, should be carefully interpreted when translating to clinical practice Furthermore, the results of LEADERS are only applicable to the comparison between BES and SES, and any extrapolation of these data to a second-generation DES would be speculative and need a stand-alone randomised trial. The authors of the Comment article conclude “although biodegradable polymer technology is scientifically appealing and the long-term results of LEADERS are encouraging, we are not yet in a position to confirm whether biodegradable polymers will replace durable polymer for DES technology.”