According to the five-year results of the BIOSCIENCE trial, sirolimus-eluting stents with a biodegradable polymer (Orsiro, Biotronik) have a similar overall safety and efficacy profile as everolimus-eluting stents (Xience, Abbott). However, the study also found that all-cause mortality was significantly higher in patients receiving Orsiro and this higher rate was driven by a higher rate of non-cardiovascular deaths (mainly cancer).
Writing in the Lancet, Thomas Pilgrim (Department of Cardiology, University of Bern, Switzerland) and others say that, although the higher mortality rates among those receiving biodegradable stents “might be a chance finding”, they add that it warrants further observation during long-term follow-up of ongoing studies.
The single-blind, multicentre, non-inferiority, all-comers randomised trial from Switzerland compared the two stents in patients with chronic stable coronary artery disease or acute coronary syndromes, with a primary endpoint of target lesion failure (a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation). Pilgrim et al found that, of the 2,008 patients who completed five years of follow-up, target lesion failure occurred in 198 (20.2%) of those treated with Orsiro and in 189 (18.8%) of those treated with Xience (rate ratio [RR] 1.07; p=0.487); there was no significant interaction between treatment effect and time. However, all-cause mortality was significantly higher in patients treated with biodegradable-polymer stents (14.1% vs. 10.3%; RR 1.36; p=0.017)—influenced by non-cardiovascular deaths. There was no difference in definite stent thrombosis was observed between groups at five years.
Biodegradable polymers are thought to reduce the potential for a polymer-induced chronic inflammatory response, with benefits that may extend beyond the degradation of the polymer. This study is the first to assess long-term efficacy and safety outcomes after the time of complete disintegration of the polymer in a comparison with the best-in-class durable-polymer device.
The investigators comment: “There were no differences in the occurrence of target lesion failure and its individual components of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revacularisation between the stent types in our study. This study extends the clinical evidence on the newest generation of drug-eluting stents combining biodegradable polymers with ultrathin-stent platforms. Although, to our knowledge, our analysis provides the longest available experience of ultrathin strut biodegradable polymer sirolimus-eluting stents, a difference in very late stent thrombosis might become apparent only during extended follow-up beyond five years.”
All-cause death was the only one of 20 outcome parameters to differ significantly between stents, a consequence of the difference in the incidence of death secondary to different types of cancer. Pilgrim et al did not prospectively record a history of cancer at baseline; hence they say “we cannot differentiate between death secondary to pre-existing, recurring, and newly developed cancer in our study population”.
Commenting in the Lancet, Clemems von Birgelen and Paulo Zocca (University of Twente, Enschende, Netherlands) say that, based on existing knowledge and other trial results, “play of chance might be the most plausible explanation for this difference”. They also note that the average age of study participants at around 66 years may have relevance; it was higher than in previous trials with five-year outcomes for all-comers, and age is directly related to an increased risk both of developing cancer and of death.
Also, Birgelen et al add that the results show that “it is desirable to obtain outcome data for novel coronary stents from more than one randomised clinical trial. Ideally, these trials should originate from different countries so as to increase diversity in study populations.”
Pilgrim presented the results of the BIOSCIENCE at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germnay). He told Cardiovascular News: “The Orsiro stent shows comparable clinical outcomes compared with the Xience stent throughout long-term clinical follow-up. A differential in timing of definite stent thrombosis as observed in earlier generation biodegradable polymer drug-eluting stent as compared to early generation durable polymer drug-eluting stent (LEADERS trial) did not translate to newer generation stent platforms. Numbers of definite stent thrombosis were low in both treatment arms, and a trend towards a differential in timing of definite stent thrombosis (with higher rates of definite stent thrombosis within the first year after stent implantation and lower rates between year one and year five in patients treated with Orsiro) needs to be interpreted with caution”