For the millions of adults living with coronary artery disease and a drug-eluting stent, the question of how long to stay on two blood-thinning medications carries real consequences — more drugs mean more bleeding risk, more side effects, and higher costs. A rigorous randomized trial now offers the clearest evidence yet that dropping aspirin after the first year may be safe even for the highest-risk patients.
The HOST-EXAM Extended trial enrolled 3,203 South Korean patients who had already completed 12 months of dual antiplatelet therapy (DAPT) following drug-eluting stent implantation and were classified as high ischemic risk due to clinical or lesion-level characteristics. Participants were randomized equally to continue clopidogrel monotherapy or to extend DAPT with clopidogrel plus aspirin for an additional 24 months. The composite primary endpoint — encompassing all-cause mortality, myocardial infarction, stent thrombosis, stroke, and clinically meaningful bleeding — occurred in 5.0% of the monotherapy group versus 5.1% in the DAPT group, a risk difference of just -0.1 percentage points that comfortably met the prespecified noninferiority margin of 2.3 percentage points.
This finding extends the earlier HOST-EXAM trial — which established clopidogrel monotherapy's non-inferiority in a broader stent population — into the more contested territory of high-risk patients where cardiologists have historically been most reluctant to de-escalate. The results align with the broader TWILIGHT and GLOBAL LEADERS trials suggesting that aspirin's marginal ischemic benefit after the initial year is often outweighed by its bleeding liability. An important caveat: this was an open-label Korean single-nation trial, and the results may not fully translate to populations with different metabolizer phenotypes for clopidogrel or distinct comorbidity profiles. Additionally, high-risk was defined by somewhat heterogeneous criteria, and event rates were relatively low overall, which limits power to detect rare but catastrophic outcomes like stent thrombosis independently. Nonetheless, published in the New England Journal of Medicine, this is a well-powered, prospectively designed trial that will meaningfully inform international guidelines and strengthen the case for aspirin discontinuation beyond 12 months in stable high-risk stent patients.