There is no evidence of superiority of Endeavor zotarolimus-eluting stent (E-ZES, Medtronic) compared with Cypher sirolimus-eluting stent (C-SES; Cordis, a Johnson & Johnson company) in definite or probable stent thrombosis rates at three years, according to the PROTECT trial presented Aug. 27 at the 2012 European Society of Cardiology (ESC) Congress in Munich.
Currently available drug-eluting stents vary according to drug, polymer and stent characteristics. “It is plausible, given the effect of drug and polymer on vascular healing, that these variations might be associated with differences in the risks of stent thrombosis and adverse clinical consequences over time,” wrote the study authors in the Lancet, which published the results simultaneously with the trial’s presentation.
The open-label, randomized, superiority PROTECT (The Patient Related OuTcomes with Endeavor versus Cypher stenting Trial) was designed to compare the long-term safety of two devices with different anti-proliferative properties—the Endeavor and Cypher stents—in a broad group of patients and lesions.
Between May 21, 2007 and Dec. 22, 2008, Edoardo Camenzind, MD, of the University of Geneva in Switzerland, and colleagues randomized 8,791 patients from 36 recruiting countries, of whom 8,709 provided consent to participate and were eligible: 4,357 were allocated to the E-ZES group and 4,352 patients to the C-SES group. Eligible patients were those age 18 years or older undergoing elective, unplanned or emergency procedures in native coronary arteries.
The researchers randomly assigned patients to either receive E-ZES and C-SES (ratio 1:1). Randomization was stratified per center with varying block sizes of four, six or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at three years, which was analyzed by intention to treat. Patients and investigators were aware of treatment assignment.
At three years, rates of definite or probable stent thrombosis did not differ between groups (1.4 percent for Endeavor vs. 1.8 percent for C-SES). Dual-antiplatelet therapy (DAPT) was used in 96 percent of the patients at discharge, 88 percent at one year, 37 percent at two years and 30 percent at three years.
“PROTECT was designed to compare the incidence of stent thrombosis between two devices with different healing characteristics, and did not find evidence of superiority in definite and probable stent thrombosis rates between E-ZES and C-SES at three years and the rates of stent thrombosis were lower than anticipated,” wrote the study authors. “However, prespecified time analysis suggests a difference is emerging over time. Differences between devices emerged during the period of one to three years, when use of DAPT was lowest, suggesting a possible important role for the use of DAPT. Thus information about stent thrombosis rate with a given drug-eluting device has to be assessed with caution and always in perspective of the concomitant DAPT treatment and duration of follow-up.”
In the accompanying commentary, Jörg Hausleiter, MD, and colleagues at the Deutsches Herzzentrum in Munich, noted that "[s]ince the study began in 2007, there has been a significant shift in interventional cardiology practice such that both study devices have largely fallen out of use worldwide, being superseded by newer devices with higher efficacy and lower rates of stent thrombosis. Nevertheless, the data remains of interest to physicians caring for the millions of patients already treated with these stents. In addition, the authors have dispelled the misconception that the in-stent tissue growth associated with less effective drug-eluting stents confers lower risk for stent thrombosis.”
Minneapolis-based Medtronic provided funding for the study.