Zotarolimus Stent: Short-Term Dual Antiplatelet Therapy Is Safe

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Low Event Rates Blur Statistical Margins

One of take-away lesson from this study is that in an anatomically low-risk population such as this, with a reference vessel diameter of 3.0 mm and an average of 1.3 treated lesions per patient, we’re getting very good with our drug-eluting stents. The expected 1-year event rate of about 10% was more than double what was actually observed.

Dr. Matthew J. Price

These low event rates in both study arms underscore how difficult it’s going to be to ever definitively prove that short-duration DAPT is safe. RESET was a noninferiority study, and even with more than 2,100 randomized patients, the statistical noninferiority margins were broad enough that it’s theoretically possible for a safety signal to have gone undetected.

Matthew J. Price, M.D., is director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif. He was the study discussant at the meeting. Dr. Price reported serving as a consultant to Bristol-Myers Squibb, Sanofi, and more than a half-dozen other companies.



CHICAGO – A 3-month regimen of dual antiplatelet therapy may be a safe and effective alternative to the standard 12 months in selected recipients of the zotarolimus-eluting Endeavor stent.

This was the main finding of the 2,117-patient randomized, prospective RESET (Real Safety and Efficacy of 3-Month Dual Antiplatelet Therapy Following Zotarolimus-Eluting Stent Implantation) trial.

Dr. Myeong-Ki Hong

RESET was an open-label, randomized trial conducted at 26 South Korean centers. It was designed as a noninferiority study, meaning it was set up to evaluate the hypothesis that 3 months of dual antiplatelet therapy (DAPT) with clopidogrel and aspirin following implantation of the Endeavor drug-eluting stent doesn’t yield worse clinical outcomes than does the standard 12 months of DAPT.

Dr. Myeong-Ki Hong volunteered that an important study limitation in RESET was the exclusion of high-risk patients from participation. Among those ineligible were patients with a history of peripheral artery disease or cerebrovascular accident, those in cardiogenic shock or with a left ventricular ejection fraction less than 40%, and patients with severe renal or hepatic renal dysfunction. The lessons of RESET may not be applicable to such individuals.

Participants in RESET underwent percutaneous coronary intervention and implantation of a drug-eluting stent for unstable angina, acute MI, or stable angina. Half of RESET participants were randomized to receive the Endeavor stent with 3 months of DAPT before discontinuing clopidogrel and carrying on with aspirin monotherapy; the other half received various other drug-eluting stents accompanied by the standard, guideline-recommended 12 months of DAPT.

The primary study end point was the 12-month composite of cardiovascular death, acute MI, stent thrombosis, ischemia-driven target vessel revascularization, and TIMI (thrombolysis in myocardial infarction) major or minor bleeding. The combined end point occurred in exactly 4.7% of subjects in each study arm, Dr. Hong reported at the annual meeting of the American College of Cardiology.

The secondary end point (comprising all-cause mortality, stent thrombosis, or MI at 12 months of follow-up) occurred in 0.8% of patients assigned to 3 months of DAPT and 1.3% of controls, a nonsignificant difference, noted Dr. Hong, professor of medicine at Yonsei University, Seoul.

A key aim of DAPT, he pointed out, is the prevention of stent thrombosis. Two cases occurred in Endeavor stent recipients, both during their 3 months on DAPT; notably, no cases occurred in this group after discontinuation of clopidogrel. In contrast, three cases of stent thrombosis occurred in the control group on 12 months of DAPT, all during months 3-12.

Downsides of prolonged DAPT include increased risk of bleeding, financial cost, and poor patient adherence. Dr. Hong cited the following situations in which (based upon RESET) the placement of a zotarolimus-eluting stent and 3 months of DAPT might be useful:

• Patients at increased risk for bleeding complications.

• Patients with a high likelihood of noncardiac surgery or other invasive procedures in the coming year.

• Patients at low anatomical risk of stent thrombosis.

• Patients who are likely to be nonadherent to the prolonged DAPT regimen.

An impetus for the RESET trial was an earlier Korean registry that reported favorable long-term outcomes in 661 patients whose clopidogrel was discontinued 3 months after implantation of a zotarolimus-eluting stent (Circ. J. 2010;74:2314-21).

Audience member Dr. Antonio Colombo of Milan, who was honored as a "Legend of Cardiology" at the conference, rose to note that most studies from Korea and Japan report stent thrombosis rates that are half those seen in Europe and North America.

"I believe it’s not easy to translate these RESET conclusions to other populations. I think some genetic or other factors may play a role in these low thrombosis rates," he observed.

The study was sponsored by the South Korean Ministry of Health and Welfare, the Cardiovascular Research Center of Seoul, and Medtronic. Dr. Hong reported having no financial conflicts. Dr. Price reported serving as a consultant to Bristol-Myers Squibb, Sanofi, and more than a half-dozen other companies.

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