Background Information on the LEADERS Study
What does LEADERS stand for?
Limus Eluted from A Durable versus ERodable Stent coating
What makes the study different?
LEADERS is the first head-to-head randomized study between two limus-eluting stents (DESs) in an “allcomers” population using clinical results as its primary endpoint.
What was the design of the study?
The multicenter European study randomized 1,707 patients eligible for percutaneous coronary intervention
(PCI) for symptomatic coronary disease to receive either a biolimus-eluting stent with abluminal
biodegradable polymer (BioMatrix Flex™) or a sirolimus-eluting stent with durable polymer (Cypher®
Select™).
What is an “all-comers” population?
The type of patient an interventional cardiologist is likely to see on a daily basis, as opposed to patients
carefully screened to take part in clinical trials. Inclusion criteria were broad, reflecting routine clinical
practice, without limitations regarding type of coronary vessel, lesion length or number of treated lesions.
Patients with acute coronary syndromes, saphenous vein grafts, bypass grafts and previously treated
lesions were also included.
What was the primary endpoint?
Non-inferiority on a clinical composite of cardiac death, myocardial infarction, or clinically-indicated target
vessel revascularization (TVR) at 9 months follow-up. This composite endpoint is commonly referred to as
“MACE” (Major Adverse Cardiac Events).
What other assessments were made?
25% of all patients (427) were randomly assigned to undergo angiographic follow-up to assess in-stent
percent diameter stenosis at 9 months.
What were the study results?
Four-year results from the LEADERS trial, published in The Lancet in December 20111, showed improved
long-term clinical outcomes for BioMatrix Flex compared to Cypher Select. This improvement was mainly
achieved by reducing the risk of cardiac events associated with very late stent thrombosis (VLST) occurring
beyond the first year of follow-up.
There was an excellent clinical follow-up rate of over 96% at four years, at which time the risk of MACE was
lower in patients treated with BioMatrix Flex than in those treated with Cypher Select (18.7% vs. 22.6%: p =
0.050). The benefit of BioMatrix Flex appeared more pronounced between years one and four. During this
one to four year period, BioMatrix Flex was associated with a significant 80% relative risk reduction in
definite VLST compared with Cypher Select (p=0.004).1
An analysis of the correlation between MACE and definite stent thrombosis events showed that the benefit
in favor of BioMatrix Flex in terms of MACE was largely driven by a lower risk of MACE associated with
definite VLST beyond the first year of follow-up.1
Primary endpoint data from LEADERS, published in The Lancet in 20082, demonstrated BioMatrix Flex to be
non-inferior to Cypher Select with respect to the incidence of MACE at nine months. This non-inferiority
has been confirmed in the one3, two4, three5 and four-year results1, during which time a diverging trend
towards a safety benefit for BioMatrix Flex was observed.
References:
1. Stefanini GG et al. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents
versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS):
4 year follow-up of a randomised non-inferiority trial. The Lancet 2011; 378: 1940-1948.
2. Windecker 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.
The Lancet 2008; 372 No. 9644:1163-1173.
3. Garg S. et al.The Twelve-Month Outcomes of a Biolimus Eluting Stent with a Biodegradable Polymer
compared with a Sirolimus Eluting Stent with a Durable Polymer. EuroIntervention 2010; 6: 233239.
4. Volker Klauss et al. 2-Year Clinical Follow-Up From the Randomized Comparison of Biolimus-Eluting
Stents With Biodegradable Polymer and Sirolimus-Eluting Stents With Durable Polymer in Routine
Clinical Practice. J Am Coll Cardiol Intv 2011; 4: 887-895
5. Wykrzykowska et al. The three year follow-up of the randomized “all-comers” trial of a
biodegradable polymer biolimus-eluting stent versus permanent polymer Sirolimus-eluting stent
(LEADERS). EuroIntervention 2011, Published ahead of print on October 27, 2011.
For further information about LEADERS, please visit www.biosensors.com