Secondary Analysis of 5-Year TWENTE Data Compares Real-World Use of DES
January 31, 2017—Online ahead of print in Journal of the American Medical Association (JAMA): Cardiology, Clemens von Birgelen, MD, et al published findings from a secondary analysis of the TWENTE randomized clinical trial of drug-eluting stents (DES) that evaluated real-world use of the Endeavor Resolute zotarolimus-eluting stent (Medtronic) versus the Xience V everolimus-eluting stent in Twente, the Netherlands.
As summarized in JAMA: Cardiology, the analysis demonstrated that the rate of the main composite clinical endpoint of target vessel failure (TVF) was similar for zotarolimus- and everolimus-eluting stents. TVF is defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. In all eligible patients, the event rate was only slightly higher than in trial participants only. At long-term follow-up of this randomized clinical DES trial, newer-generation stents were found to be safe and efficacious, and the outcomes of nonenrolled eligible patients support the trial’s validity.
The TWENTE trial is an investigator-initiated, patient-blinded, randomized, comparative trial that enrolled patients from June 18, 2008 to August 26, 2010. Most patients had non–ST-elevation acute coronary syndromes and complex lesions.
According to the investigators, of all 1,709 eligible patients, 1,391 (81.4%) were treated in the TWENTE trial with ZES (n = 697) or EES (n = 694) cobalt-chromium stents. The remaining 318 eligible patients (18.6%) were not enrolled but underwent nonrandomized treatment with the same DESs. Data were analyzed from August 26, 2015 to October 11, 2016. Event rates were derived from log-rank analysis and may differ from straightforward calculation. The 5-year follow-up of the TWENTE participants was prespecified in the trial protocol; that of the nonenrolled participants was ad hoc.
In JACC: Cardiology, the investigators reported that of the 1,709 eligible participants, 1,233 (72.1%) were men, 476 (27.9%) were women, and the mean age (standard deviation) was 64.6 (10.6) years.
Among the 1,370 of 1,391 TWENTE trial participants (98.5% follow-up), TVF was similar between those in the ZES (16.1%) and EES (18.1%) groups (P = .36). Stent thrombosis rates were low: they were definite (1% vs 0.6%; P = .37) and occurred after more than 1 year in three patients (0.4%) with ZES versus four patients (0.6%) with EES (P = .69).
The 318 nonenrolled eligible patients (308 patients [96.9%] of whom were followed-up) were older and had a more advanced disease than trial participants. Their TVF rate was higher than that of trial participants (23.3% vs 17.1%; P = .02), which partly reflects a difference in cardiac mortality (7.7% vs 4.5%; P = .03).
Similar 5-year rates were found for myocardial infarction (6.7% vs 7.2%; P = .8) and target vessel revascularization (9.7% vs 11.4%; P = .36) between trial participants and nonenrolled eligible patients. In all eligible patients (ie, trial participants plus nonenrolled eligible patients), the TVF rate was only slightly higher than in trial participants only (18.3% vs 17.1%).
"Long-term outcome data from nonenrolled eligible patients support the validity of the TWENTE trial findings and present a strong case for the long-term safety and efficacy of the newer-generation DESs used," concluded the investigators in JAMA: Cardiology.