ACC: New data may RESET thinking on DAPT duration
To bolster the methodology of the study, the study’s lead investigator Myeong-Ki Hong, MD, PhD, from the division of cardiology at Severance Cardiovascular Hospital in Seoul, South Korea, cited several trials that used Endeavor and have shown beneficial efficacy and safety, “despite a relatively short duration of DAPT” (Circulation 2006;114:798-806/Am J Cardiol 2007;100:S56-S61/J Am Coll Cardiol 2010;55:543-554). He also cited the recent DATE registry, which assessed 661 low-risk patients with Endeavor and three months of DAPT, and showed favorable long-term clinical outcomes after cessation of clopidogrel at three months post-intervention.
Thus, the RESET investigators hypothesized that three months of DAPT after an Endeavor implantation may be non-inferior to 12 months of DAPT after implantation with another type of DES (standard therapy).
This prospective, open label, randomized trial included 26 participating centers in South Korea. Using an interactive web-based response system, study participants were randomly assigned in a 1:1 ratio to receive either the Endeavor or another currently available DES. The primary end points were a composite of death from cardiovascular causes, MI, stent thrombosis (defined as definite or probable stent thrombosis by ARC definition), ischemia-driven target-vessel revascularization or bleeding (defined as TIMI-defined major or minor bleeding) at one year post-procedure.
The researchers randomized patients with 1,058 in the standard therapy and 1,059 patients in the arm using Endeavor plus three months of DAPT. The clinical follow-up at one year was completed in 98.5 percent of patients with 98.5 percent remaining the standard therapy arm and 98.6 percent remaining in the other arm.
For the primary endpoint, the difference was zero—with both arms having incidence rates of 4.7 percent at one year. Examining the cumulative event rate of any death, MI or stent thrombosis at 12 months, the standard therapy arm was 1.3 percent and the arm using Endeavor plus three months of DAPT was 0.8 percent.
In the study, the mean duration of DAPT in the Endeavor group was 93 days and 364 days in the standard therapy group. Interruption of the DAPT regimen in the Endeavor group occurred in 62 of the 1,059 patients, and the reasons for interruption were: physicians’ mistake or failure of monitoring (26 patients); physicians’ discretion (22 patients); patients’ disagreement (13 patients); and repeat revascularization (one patient).
Of note, when the researchers broke out stent thrombosis independently, there were two events within 30 days of stent implantation for the Endeavor arm and no other incidence out to one year. For the standard therapy arm, there was stent thrombosis in the first three months and three events occurring in the third through 12th month.
About these results, study discussant Antonio Colombo, MD, director of investigational angioplasty at Lenox Hill Hospital in New York City, said that the stent thrombosis rates being reported from Japan, Korea and other Asian countries, are on average half of that being reported in Western countries. “Thus, it is not easy to translate the results to Western patients, and may indicate a genetic difference.”
Overall, the Endeavor arm was non-inferior to standard therapy for the primary end point (defined as a composite of death from CV cause, MI, stent thrombosis, TVR or bleeding at one year). Hong added that the occurrence of stent thrombosis was similar between the two groups, and there were no significant differences of the other composite events or individual component of primary endpoint.
Hong acknowledged some limitations of the study. First, one year of clinical follow-up may not be sufficient to assess fatal late outcomes, such as very late stent thrombosis. Because the patients with very high risks were not included, the generalized application of these results to the entire population “demands careful attention,” he said. Also, the comparator group was not treated with a single DES type and there was no three-month vs. 12-month DAPT either within Endeavor within other DES.
Discussing the clinical implications, Hong said that utilizing the Endeavor stent with three months DAPT could be useful for selected patients, as an alternative PCI strategy for: those at risk for bleeding complications; those at risk of poor compliance with medication, especially in the elderly population; those with a high probability of unexpected non-cardiac surgery or invasive procedures; and those with a low risk of stent thrombosis.
Study discussant Matthew J. Price, MD, an interventional cardiologist at Scripps Health in San Diego, said he had two takeaways from the RESET trial. “One, it once again shows that in this population with fairly low angiographic risk, the event rates are quite low. We’re reproducing much better outcomes in patients with low anatomical risk. Second, it is tremendously difficult to provide definitively proof that shortened duration of DAPT is safe.”
The study was in part funded by Medtronic.