EXCELLENT Outcomes Regardless of Antiplatelet Therapy Duration After DES

NEW ORLEANS, LA—Patients implanted with either everolimus- or sirolimus-eluting stents experience similar clinical outcomes whether they receive 6 or 12 months of dual antiplatelet therapy, according to late-breaking findings presented April 5, 2011, at the American College of Cardiology Scientific Session/i2 Summit.

For the EXCELLENT trial, researchers led by Hyeon-Cheol Gwon, MD, PhD, of the Sungkyunkwan University School of Medicine (Seoul, South Korea), randomized 1,443 patients treated at 19 Korean centers in a 2 by 2 factorial design to receive dual antiplatelet therapy for 6 months (n = 722) or 12 months (n = 721) and, within each medication group, to receive either everolimus- or sirolimus-eluting stents in a 3 to 1 ratio. All patients had at least 50% stenosis by visual estimation, evidence of ischemia, target lesions located in a native coronary artery, and reference vessel diameters ranging from 2.25 to 4.25 mm.

Baseline characteristics were similar regardless of whether patients were assigned to receive either 6 or 12 months of dual antiplatelet therapy, with the exception of previous MI, which was higher in the 6-month group (P = 0.017). Over 99% of patients were still on aspirin therapy at 1 year. In the 6-month group, 26.6% of patients continued to take clopidogrel beyond their allotted time frame, while 6.2% of patients in the 12-month group stopped clopidogrel ahead of schedule.

Equivalent Across the Board

In data previously presented at the 2010 Transcatheter Cardiovascular Therapeutics symposium in Washington, DC, the study's co-primary endpoint of in-segment late luminal loss at 9 months was similar for everolimus- and sirolimus-eluting stents at 0.10 ± 0.36 mm and 0.05 ± 0.34 mm, respectively (P = 0.023 for noninferiority).

Dr. Gwon presented the study's other co-primary endpoint, target vessel failure (TVF; composite of cardiac death, MI, or TVR) at 12-month follow-up. On Kaplan-Meier analysis, 6 months of dual antiplatelet therapy was noninferior to a 12-month regimen (P = 0.0031). Overall rates of TVF and several secondary endpoints were similar between the 2 groups (table 1).

Table 1. Outcomes at 12 Months

^a Primary endpoint.

^b Academic Research Consortium-defined definite or probable stent thrombosis.

Subgroup analysis, however, showed that patients with diabetes were more likely to experience TVF by 12 months with the 6-month regimen (8.9%) than with the 12-month regimen (2.9%; P = 0.001 for interaction). The difference was evident, although not significant, at 6-month follow-up.

Dr. Gwon acknowledged several limitations to the study. The incidence of the primary endpoint was lower than expected, and the study was underpowered to evaluate hard endpoints such as death, MI, and stent thrombosis. Crossover to longer clopidogrel duration is also a concern, he said, adding longer follow-up would also be more informative.

“A larger-scale randomized controlled trial is required to test the impact of shorter duration of clopidogrel therapy on hard endpoints,” he concluded.

Some Caveats

Panelist Sanjay Kaul, MD, of Cedars-Sinai Medical Center (Los Angeles, CA), questioned the trial's choice of endpoints. “Dual antiplatelet therapy is intended to target thrombotic endpoints, and you've included target vessel revascularization [in the primary composite], which is not the intended target,” he said.

In addition, the study design based the margins of noninferiority on absolute rather than relative risk difference. Because of the lower than expected adverse event rate, Dr. Kaul explained, the possibility of noninferiority was comparatively higher with this methodology. “If you fixed your margin as a relative  risk margin, you would have failed to meet the primary endpoint,” he said, noting that the issue of absolute vs. relative risk in noninferiority trials is controversial.

“Given these issues, I think it is not possible to draw any definitive conclusions from this study, and I agree with you that the results should be considered primarily as hypothesis generating,” Dr. Kaul concluded, adding that even if it were acceptable to have a slightly elevated risk of ischemic events with 6 months of dual antiplatelet therapy, that risk must be offset by a decrease in bleeding. Such a trade-off was not observed in the current study, he pointed out, admiting that reduced cost and added convenience might support the shorter regimen.

Source:

Gwon H-C. The randomized comparison of six-month versus 12-month duration of dual antiplatelet therapy after implantation of drug-eluting stents: From comparison of everolimus- versus sirolimus-eluting stents for coronary revascularization (EXCELLENT) trial. Presented at: American College of Cardiology Annual Scientific Session/i2 Summit; April 5, 2011; New Orleans, LA.

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