STOCKHOLM – Everolimus-eluting stents were associated with significantly lower risks of myocardial infarction, target vessel revascularization, and stent thrombosis than were sirolimus-eluting stents, during 3 years of follow-up in the LESSON-1 study.
Dr. Stephan Windecker
A particularly striking finding in LESSON-1 (Long-Term Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents for Coronary Revascularization) was the 70% lower rate of Q-wave MI in the everolimus-eluting stent (EES) group, Dr. Stephan Windecker noted, in presenting the study results at the annual congress of the European Society of Cardiology.
Some observers called the LESSON-1 findings interesting but nondefinitive, since the study was nonrandomized, single-center, observational, and reliant upon propensity score matching.
Dr. Windecker concurred. He noted there are four ongoing randomized trials comparing outcomes in everolimus- versus sirolimus-eluting stent (SES) recipients.
The LESSON-1 study involved 1,601 consecutive patients undergoing percutaneous coronary intervention with the Xience EES and 1,532 consecutive patients who received a Cypher SES. After propensity score matching, the final study population consisted of 1,342 matched subjects in each of the two treatment arms, explained Dr. Windecker of Bern (Switzerland) University Hospital.
The primary study end point was the 3-year rate of death, MI, or target vessel revascularization. It occurred in 14.9% of the everolimus group and 18.0% of the sirolimus cohort. The resultant 17% relative risk reduction fell just shy of statistical significance, owing to closely similar overall mortality rates in the two groups, he reported.
However, the EES group fared significantly better than SES recipients in terms of key prespecified secondary end points. For example, MI occurred in 3.3% of the everolimus recipients compared with 5.0% of the sirolimus group, for a significant 38% risk reduction. The MI rates diverged early and the gap increased steadily during follow-up.
Target vessel revascularization occurred in 7.0% of EES and 9.6% of SES recipients, for a significant 25% risk reduction.
Similarly, the everolimus group had a significantly lower rate of definite stent thrombosis during 3 years of follow-up: 0.5% vs. 1.6%. The rate of definite or probable stent thrombosis was 2.5% in the everolimus group and 4.0% with sirolimus. These differences were driven largely by the EES group’s zero incidence of very late stent thrombosis occurring after 1 year, compared with a 0.7% rate of definite very late stent thrombosis in the SES arm.
The lower incidence of MI in the EES group was partially explained by their significantly lower rate of stent thrombosis. Indeed, MIs occurring in association with definite stent thrombosis were 75% less frequent in the EES group, the cardiologist continued.
If this absence of stent thrombosis occurring beyond 1 year in EES recipients in LESSON-1 holds up in the ongoing large randomized trials, it will have important implications for the appropriate duration of dual antiplatelet therapy in patients with EES, Dr. Windecker said.
The divergent outcomes in patients with EES and SES may be due to the fact that “the two drugs are similar but nevertheless different,” he noted. “Everolimus is a semisynthetic analogue of sirolimus with a lower pharmacologic potency, and it is applied at lower doses than the sirolimus-eluting stent. So we have this counterintuitive finding that a drug that is somewhat less potent applied at a lower concentration nevertheless achieves higher efficacy.”
But there are other differences between EES and SES. The EES, which are of a newer generation than SES, utilize a substantially thinner polymer coating and have markedly less strut thickness.
“Which one of these components drives the difference is unknown at this point in time, but it may very well turn out to be a combination of all three,” according to Dr. Windecker.
He noted that EES have already been convincingly shown to provide clinical outcomes that are superior to paclitaxel-eluting stents in four randomized trials. He provided an updated meta-analysis with 3 years of follow-up in 6,789 patients in the COMPARE and SPIRIT II, III, and IV randomized trials, which showed that the rate of cardiac death or MI was 37% lower in the EES group. In addition, target lesion revascularization was 49% less likely with EES.
Discussant Dr. Petr Widimsky said the biggest of LESSON-1’s several limitations is the use of historical controls. While most EES recipients in the study received stents in 2007-2009, most SES recipients got their stents in 2004-2005.
“The knowledge about stent thrombosis and the skills in preventing it by appropriate implantation techniques improved during this period,” noted Dr. Widimsky of Charles University, Prague.
Disclosures: Dr. Windecker said that in the past he has been a consultant to numerous medical device companies that market stents.