ACC: Will six-month DAPT ever be EXCELLENT?

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NEW ORLEANS--Administering a six-month dose of dual-antiplatelet therapy (DAPT) showed similar outcomes as a 12-month dose after drug-eluting stent implantation and while the results were underpowered, in a few years, safely discontinuing DAPT could be feasible, according to the results of the EXCELLENT trial presented this morning at the annual American College of Cardiology scientific sessions.

While the current guideline recommends at least 12 months of DAPT after DES implantation, however, there is no prospective clinical trial to evaluate this recommendation.

Researchers from the Samsung Medical Center, Sungkyunkwan University School of Medicine in Seoul, South Korea, during the EXCELLENT trial tested the safety and efficacy of six-month dual-antiplatelet dose duration compared with a 12-month duration in 1,443 patients at 19 centers who had more than 50 percent stenosis, evidence of MI and who had target lesions located in their native coronary arteries.

When patients were randomized, 722 patients received DAPT for six months and 721 patients received DAPT for 12 months. The primary endpoint used was 12-month target vessel failure (TVF)—a composite of cardiac death, MI or target vessel revascularization (TVR).

The rates of target vessel failure were reported to be 4.7 percent in the six-month arm and 4.4 percent in the 12-month group, reported Hyeon-Cheol Gwon, MD, principal investigator of the study. Additionally, major adverse cerebrovascular cardiovascular events (MACCE) rates were 7.5 percent at six months and 8.4 percent at 12 months.

During a subgroup analysis, the researchers evaluated the primary endpoint in patients who received an everolimus-eluting stent (EES) or a sirolimus-eluting stent (SES). The rates of TVF were 2.9 percent vs. 2.1 percent for six-month DAPT and 12-month DAT in patients receiving EES, these same rates for those receiving a SES were 4.2 percent vs. 1.9 percent at six and 12 months.

Gwon, also reported that the rates of stent thrombosis and TIMI rates were similar between both groups.

He said that limitations of the study included the fact that the incidence of primary endpoint was lower than expected and the trial may be underpowered to test hard endpoints of death, MI or stent thrombosis.

When asked why target vessel revascularization was chosen as the primary endpoint, Gwon said, “Practically, we don’t have enough data to enroll with sufficient power to study hard endpoints, so we selected a softer endpoint to gain some ideas about the duration of clopidogrel.”

While the author noted that the discontinuation of clopidogrel could be attempted when risk profiles of patients are considered, he said this small, underpowered study provides only a hypothesis about clopidogrel therapy. “We have many more questions than answers for the issue of clopidogrel,” Gwon concluded.

Panelist Sanjay Kaul, MD, of Cedars-Sinai in Los Angeles said, “Dual-antiplatelet therapy's intended target is thrombotic endpoint and you used target vessel revascularization [as the primary endpoint] and that is not the intended target of dual-antiplatelet therapy.” Kaul asked Gwon why TVR was chosen as the primary composite endpoint.

“You are quite right that this study is underpowered to test hard endpoints that we are really interested in—MI, cardiac death, among others,” said Gwon. However, he noted the several different trials comparing the shorter and longer duration of DAPT. “We know we need a larger number of patients to test this … so we can label this as hypothesis generating rather than answering a question.”

"In a noninferior trial, the challenge is always how to define margins and we fix the margins to have an absolute risk margin or a relative risk margin,” said Kaul. He noted that there has been controversy as to whether you fix the margin as a relative or absolute risk because if you fixed the margin as a relative margin you may fail to meet the primary endpoint.

Because the EXCELLENT trial was fixed to an absolute risk margin, the primary endpoint was met, said Kaul. “Given these issues, I think it’s not possible to draw any definitive conclusions from this study.”

Gwon concluded that the take home message of the study is at least in low-risk patients, maybe in a few years, "clopidogrel can be safely discontinued at about six months, especially for patients at a high risk of bleeding.”