SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.
A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.
In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).
After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.
The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.
Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.
In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).
The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.
The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.
The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.
The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.
Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).
They called the differences in rates of late stent thrombosis "intriguing."
Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."
Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.
The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.