New data released at the 2009 American College of Cardiology meeting demonstrated exceptional long-term safety and effectiveness results for the Endeavor drug-eluting coronary stent from Medtronic, Inc., in a large multicenter, real-world study, in which no defined patient selection criteria were specified, and angioplasty was used at medical discretion. Two-year results for more than 2,000 patients in the international, E-Five study show that the Endeavor stent was associated with a low rate of both overall (0.7 percent) and very late stent thrombosis (VLAST) at 0.1 percent.
Long-term controlled clinical studies of other approved drug eluting stents (DES) reveal a small but consistent (0.3 percent/year) increase in the frequently-fatal VLAST complication. The E-Five findings run counter to expectations based upon these prior studies of other DES which have also reported an approximate doubling (0.6 percent/year) in the rate of VLAST when these devices are used in real-world patient populations.
The long-term safety results for the Endeavor stent are distinct in that the overall rate of stent thrombosis and the rate of VLAST was found to be low and similar to those rates observed in pooled data from controlled, clinical trials in the ENDEAVOR program.
On other safety endpoints, the two-year results for this prespecified subset of E-Five patients were similarly favorable, with low and stable rates of cardiac death (1.2 percent vs. 1.5 percent) and myocardial infarction (1.2 percent vs. 1.5 percent) at one and two years, respectively.
Duration of dual-antiplatelet therapy (DAPT) for these E-Five patients underscores the safety benefits of the Endeavor stent: 52.6 percent of the patients were on DAPT at one year and 22.1 percent at two years.
These safety and efficacy results from E-Five – presented in “Two-Year Extended Follow-up in Patients Receiving a Zotarolimus-eluting Stent in the E-Five Registry” (i.2 poster 2510-644) – closely resemble those from a pooled analysis of the ENDEAVOR clinical program. They also compare favorably to the results of similarly designed registries for other drug-eluting stents.
“Registries generally enroll more challenging ‘real-world’ patients than randomized trials,” explained Prof. Rothman of the UK’s London Chest Hospital and one of E-Five’s principal investigators. “For the prespecified subset of patients in E-Five who were followed to two years, the clinical outcomes are consistent with two-year results from the broader ENDEAVOR clinical program, which consists largely of randomized trials.”
E-Five enrolled more than 8,000 patients at more than 200 sites in Europe, Asia Pacific, the Middle East and South America. Extended two-year follow-up was planned for a prespecified subset of approximately 2,000 patients at 26 centers in 14 countries to determine the durability of the Endeavor stent’s safety and efficacy in a “real-world” population, which reflects the variability of patient types and lesion characteristics in standard clinical practice.
The E-Five (n=8,314) primary endpoint of major adverse cardiac events (MACE) was 7.5 percent at one year (n=7,832). For the prespecified subset (n=2,116), the MACE rate was 6.7 percent at one year and 8.5 percent at two years. Patient demographics were similar for the entire cohort and the prespecified subset, with slightly more complexity in the demographics of the entire cohort.