Conference Coverage

Equally Low Thrombosis Seen With Zotarolimus-, Sirolimus-Eluting Stents

Publish date: August 27, 2012
By
Michele G. Sullivan

View on the News

Zotarolimus or Sirolimus? That Is the (Now Moot) Question

Results of the PROTECT study are academic now, but perhaps still interesting to physicians caring for the millions of patients who still carry the zotarolimus- and sirolimus-eluting stents, Dr. Robert A. Byrne and his colleagues wrote in an accompanying editorial.

"Since the study began in 2007, a significant shift has occurred in interventional cardiology practice, such that both study devices have largely fallen out of use worldwide, being superseded by new devices with increased efficacy and decreased rates of stent thrombosis," wrote Dr. Byrne. "This shift undoubtedly limits the immediate clinical relevance of these findings."

Dr. Byrne and his coauthors also said that PROTECT investigators problematically searched too hard for any interesting tidbits in their secondary analyses.

"The authors report a negative clinical trial with no differences in the primary endpoint. This finding is supported by an absence of difference in the main secondary endpoints. For this reason, the value of all additional analyses presented in the article is restricted, and to highlight differences in the temporal distribution of stent thrombosis between the two devices is inadvisable. This analysis was not prespecified and the probability of a chance finding is high."

The time-driven conclusions can be seeing as a never-ending division problem, they suggested.

"If one notes that stent thrombosis beyond 1 year is higher with [the sirolimus-eluting stent] ... then one must also observe that the number of patients with stent thrombosis up to 1 year is higher with [the zotarolimus-eluting stent]. To take the argument further, one must then question whether it is preferable for a patient to suffer stent thrombosis during the first year or after it: reductio ad absurdum" – arguing on and on that the finding is true because a false result follows from its denial, they wrote.

Dr. Byrne is an interventional cardiologist at Deutsches Herzzentrum, Munich. He had no financial disclosures, but a coauthor disclosed that he has received lecture fees from Medtronic, as well as other device and pharmaceutical companies.


 

FROM THE LANCET

Rates of stent thrombosis were low and similar between patients implanted with zotarolimus-eluting stents and those with sirolimus-eluting stents in a large, randomized controlled trial.

Over a 3-year period, thrombosis occurred in less than 2% of each group. Furthermore, there were no significant between-group differences in overall mortality, myocardial infarction, or cardiac death, Dr. Edoardo Camenzind and colleagues reported in the August 27 online issue of the Lancet. The study results were simultaneously presented at the annual congress of the European Society of Cardiology.

The 1.4% rate of stent thrombosis noted with the zotarolimus stent matched the expected rate of 1.5%, but the rate with the sirolimus stent was lower than anticipated, with an expected rate of 2.5% and an observed rate of 1.8%, wrote Dr. Camenzind of the University of Geneva and his coauthors (Lancet Aug. 27, 2012 [doi: 10.1016/S0140-6736(12)61336-1]).

But the Patient Related Outcomes With Endeavor Versus Cypher Stenting Trial (PROTECT) did show some time-related differences between the two devices, finding more thromboses in the first year with the zotarolimus stent (Z-ES, Endeavor), but more in years 2 and 3 with the sirolimus stent (S-ES, Cypher).

"Interestingly, the pattern of events over time was distributed differentially, with both devices having the same incidence of stent thrombosis, but C-ES having fewer late, but more very late, stent thrombosis than Z-ES," the authors noted. "The higher incidence of late stent thrombosis in the Z-ES group was driven by an increased incidence of definite stent thrombosis."

The study enrolled 8,709 patients who underwent an elective, unplanned, or emergency stenting of coronary arteries. They were a mean of 63 years old. The most common reason for stent placement was acute myocardial infarction (26%). Other reasons for stenting included unstable or stable angina or silent ischemia.

At discharge, 96% were on dual antiplatelet therapy. This number had dropped to 88% at 1 year, 37% at 2 years, and 30% by 3 years.

At the end of follow-up, definite or probable stent thrombosis had occurred in 61 (1.4%) of the Z-ES group and in 75 (1.8%) of the S-ES group – not a significant difference. Nor were there significant differences in any of the main secondary end points of total death and nonfatal MI, or cardiac death and nonfatal MI.

The study revealed a distinct time-associated pattern of thrombosis. In the first month after the procedure, definite or probable thrombosis occurred in 31 of the Z-ES group and 26 of the S-ES group. From days 31 to 360, the numbers were 17 and 5, respectively. During the last 2 years of follow-up, there were 13 definite or probable thromboses in the Z-ES group and 44 in the S-ES group.

Over the entire study period, the Z-ES was associated with a lower incidence of definite stent thrombosis than the S-ES (0.7% vs. 1.2%), but the S-ES had a lower incidence of target vessel revascularization (7.1% vs. 8.2%). None of these differences were significant, however.

Those findings also showed time-related differences. During the first year of the study, significantly more target vessel revascularizations occurred in the Z-ES group (5.8% vs. 3.4%), but that difference was reversed in years 2-3 (4.0% S-ES vs. 2.9% Z-ES).

Although slight, the differences observed in PROTECT are still important, the investigators said: "Given the seriousness of clinical manifestation of stent thrombosis, typically death or myocardial infarction, any reduction has clinical relevance. Furthermore, hundreds of thousands of patients worldwide have been implanted with these devices."

Follow-up on these patients will continue for another 2 years. This "will show whether curves of definite and definite or probable stent thrombosis further diverge and will translate into differences in clinical safety outcomes," Dr. Camenzind and his associates said.

The study was funded by Medtronic, maker of the Endeavor stent. Dr. Camenzind had no financial disclosures but several of his coauthors noted receiving financial remuneration from Medtronic and from other pharmaceutical companies and device manufacturers.

Next Article:

U.S. Medicare Leg Amputations Down From 2000 to 2008