Extending DAPT for an additional year reduced major adverse cardiovascular events (MACE) without increasing bleeding risk compared with aspirin alone among patients with multivessel coronary artery disease (MVCAD) who had no ischemic or bleeding events one year after PCI with a drug-eluting stent, according to results of the DAPT-MVD trial published July 15 in NEJM.

Across 97 centers in China, the open-label trial randomized 8,250 patients with MVCAD who were event-free at 12 months to continue clopidogrel plus aspirin (n=4,125) or to receive aspirin monotherapy (n=4,125) for an additional 12 months. The mean age of patients was 61 years and a third were women.

At a median follow-up of 34.3 months, the composite primary efficacy outcome of death from cardiovascular causes, nonfatal myocardial infarction (MI) or nonfatal stroke occurred in 5.8% of patients in the DAPT group and 6.8% of those in the aspirin monotherapy group (hazard ratio [HR], 0.82; p=0.03). The difference was driven largely by a 32% lower risk of MI with extended DAPT.

For the primary safety endpoint, clinically relevant or major bleeding occurred in 51 patients in the DAPT group and 57 patients in the aspirin monotherapy group (36-month Kaplan-Meier cumulative incidence, 1.4% vs. 1.5%; HR, 0.89; p=0.54).

Regarding the reduction in MI risk, trial investigators Jinwei Tian, MD, FACC, et al., write that it was “driven mainly by fewer events arising from nontarget coronary segments rather than from stented target sites.” They note that “beyond its direct antithrombotic effects, inhibition of the adenosine diphosphate receptor during the second year after an acute coronary syndrome – a high-risk period for plaque progression – may stabilize untreated vulnerable plaques, a beneficial effect that may persist after its discontinuation."

In an accompanying editorial comment, Kyung Woo Park, MD, PhD, FACC, and Jeehoon Kang, MD, question “whether the current findings can be generalized to other populations.” They note that treatment was evaluated exclusively in Chinese patients, "a population with a known high prevalence of CYP2C19 loss-of-function alleles, which reduce clopidogrel bioactivation, and a low prevalence of obesity."

“Nevertheless,” they add, “the identification of a specific population with high ischemic risk but low bleeding risk that can benefit from extended DAPT is a step forward in our field.”