MedWire - ESC (Munich, Germany), September 1, 2008: A novel, biodegradable, biolimus-eluting stent (BES) is “ non-inferior” to the older sirolimus-eluting stent (SES), according to the 9-month follow-up results of the LEADERS (Limus Eluted from A Durable vs ERodable Stent coating) trial, presented during the Hot Line II session here at the European Society of Cardiology (ESC) congress.
The results of the trial were published online in
The Lancet to coincide with their presentation at the ESC congress. [1] A review of the key findings and their significance is given in this report.
LEADERS: Novel, biodegradable, biolimus stent as good as sirolimus stent?
Dr. Stephan Windecker, Bern University Hospital, Switzerland
Biolimus is a semi-synthetic analog of sirolimus and is highly lipophilic, explained Professor Windecker, who presented the findings of the LEADERS trial. The drug is incorporated into a stent that uses a biodegradable polymer and which allows its release over a period of 6-9 months following placement. The rationale for the novel stent is that late-stent thrombosis - a significant clinical problem with drug-eluting stents in the long term -will be reduced because the stent will biodegrade with time.
The objective of the LEADERS study was to compare the use of the novel BES with the more conventional SES in the management of patients who had stable and unstable acute coronary syndromes (ACSs) and who were undergoing percutaneous coronary intervention (PCI).
“The inclusion criteria were broad, and exclusion criteria few, to reflect routine clinical practice,” Professor Windecker said. As such, patients could be included if they had coronary artery disease, including stable angina, silent ischemia, and an ACS such as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) or unstable angina. Patients needed to have at least one lesion with a stenotic diameter of 50% or more and a reference vessel diameter of between 2.25 mm and 3.5 mm; however, there were no limitations on the number of lesions or vessels that should be involved, or indeed on the length of the target lesions.
Patients with known allergies to stainless steel, sirolimus, biolimus, contrast media, or the three standard antithrombotic agents (i.e. aspirin, clopidogrel and heparin) used before, during or after PCI were excluded. Pregnancy and any planned, elective, surgical procedure in the 6 months following PCI were also exclusion criteria, as was participation in another clinical trial.
The mulitcenter, non-inferiority study was performed in 10 European countries and involved 1707 patients. 857 of these patients were given the BES, and the remainder were given a SES. Clinical and angiographic follow-up data at 9 months were available for 98.8% and 78.5% of the patient cohort, respectively. One-year follow-up data are expected to be presented at the Transcatheter Cardiovascular Therapeutics 2008 congress in October.
Professor Windecker noted that patient characteristics at baseline were similar between the two groups. The mean age of the patients was 65 years, 75% were male, approximately 73% had hypertension, one quarter had diabetes, and two thirds had hypercholesterolemia. Approximately 33% of patients in each arm had a previous myocardial infarction (MI), 11% had previous coronary artery bypass grafting, and 45% had chronic stable angina. ACSs were present in the remainder of patients, approximately one fifth had unstable angina, 17-18% had NSTEMI, and 16-17% had STEMI. The majority (63-69%) of patients had one lesion, with 22-29% having two.
The primary clinical endpoint of the trial - a composite measure of cardiac death, MI or the need for target vessel revascularization (TVR) at 9 months - was reached by 9.2% of the patients given a BES, and by 10.5% of those given an SES (
p=0.003). The rate ratio for the primary endpoint was 0.88, with a 95% confidence interval (CI) of 0.64-1.19.
All other efficacy and safety endpoints at 9 months were comparable between the two groups, showing that the BES was non-inferior to the SES. Of note, the development of definite stent thrombosis did not differ between those given the BES and those given a SES (1.9% vs. 2.0%; rate ratio: 093; 95% CI: 0.47-1.85). There was also no statistically significant difference in the development of “ probable” or “ possible” stent thrombosis at 0-30 days, >30 days to 9 months, and over the entire 9-month follow-up period. Angiographic follow-up also showed no difference between the groups.
Dr. Windecker concluded, “Since non-inferiority was achieved for the clinical and outcome measures in a non-restricted patient population with predominant off-label characteristics, the findings of the present study provide a high level of generalizability to routine clinical practice.”
Commenting on the study, Dr. Laura Mauri, of Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, noted that it was the first DES comparative trial to include a wide range of patients. “This is the first truly ‘all comers’ randomized controlled trial of DES and deserves congratulations,” she said. The trial was “ well-executed” and had a “solid trial design” , and the rapid enrollment to the study (all 1707 patients were recruited within 6 months) is to be commended.
Dr. Mauri pointed out that there were two major limitations of the study, however, including its “generalizability” and the “durability of relative safety and efficacy” compared with the more established SES. The latter stent, she noted had over 4 years’ of follow-up data, and “ the hypothesis” that the BES offered better safety in the long term was “intriguing, but not proven by this study.”
She commented that the optimal duration of dual anti-platelet therapy remained an open question and that it was “prudent to continue to follow current guidelines for DES, particularly in the ACS setting.”
Reference
- Windecker S, Serruys PW, Wandel S, et al. Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial. Lancet 2008. Early Online Publication, 1 September 2008.
