WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.
“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team’s SORT OUT IV trial.
Dr. David Cohen
Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.
The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.
Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.
The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.
At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Bryne of Deutsches Herzzentrum in Munich.
The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).
There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne, who reported no disclosures. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)
The ISAR-TEST 4 study is powered for noninferiority and included patients with de novo coronary artery stenosis of at least 50% and symptoms or objective evidence of ischemia. Patients with left main stem disease and patients with cardiogenic shock were excluded.
In a press conference announcing the findings, Dr. David Cohen of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., who was not involved in either study, said the studies were the first “reasonably sized comparisons” between a first-generation sirolimus-eluting stent and a second-generation everolimus-eluting stent.
Asked whether physicians should be using the so-called first-generation stents at this point in time, Dr. Cohen said he believes that the question about how the everolimus-eluting stent compares with the paclitaxel-eluting stent “has been pretty well answered through several large studies,” including SPIRIT IV and COMPARE, but that larger studies are still needed to compare the everolimus-eluting stent with the older sirolimus-eluting stent. In the meantime, he added, “more and more data [are] showing that the everolimus-eluting stent is a very safe stent.”
Dr. Jensen disclosed that she has a financial interest/arrangement or affiliation with Cordis, Johnson and Johnson, and Abbott.
The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.