Clopidogrel monotherapy after PCI was associated with a significantly lower composite risk of all-cause death, nonfatal MI, stroke, readmission for acute coronary syndrome (ACS) and major bleeding compared with aspirin monotherapy, according to 10-year follow-up results of the HOST-EXAM trial presented as featured clinical research at ACC.26 and published simultaneously in The Lancet.

Conducted between 2014-2018 at 37 sites across South Korea, the open-label HOST-EXAM trial focused on 5,438 patients (≥20 years old; mean age, 63.5 years; 25.4% women) who had completed 6-18 months of dual antiplatelet therapy (DAPT) without adverse clinical events following PCI with a drug-eluting stent. Participants were randomized 1:1 to either clopidogrel 75 mg once daily (n=2,710) or aspirin 100 mg once daily (n=2,728).

Over a median follow-up of 10.5 years, clopidogrel was associated with a lower incidence of the composite primary endpoint compared with aspirin (Kaplan-Meier estimate, 25.4% vs. 28.5%; hazard ratio [HR], 0.86).

Clopidogrel was also associated with a lower rate of the thrombotic endpoint defined as cardiovascular death, ischemic stroke, ACS readmission, and stent thrombosis (17.3% vs 20%), as well as any bleeding (9.1% vs. 10.8%). Researchers said all-cause mortality was similar between both groups.

In other findings, researchers said the cumulative long-term benefit of clopidogrel “was reflected in a lower number needed to treat at 10 years compared with that at two years.” The treatment effect was consistent across most subgroups, with a potentially greater benefit observed among patients with chronic kidney disease. Additionally, treatment adherence was higher among those assigned to clopidogrel compared with aspirin.

“These findings suggest that clopidogrel might be considered as a preferred agent for long-term antiplatelet monotherapy during the chronic maintenance phase after PCI,” write Jeehoon Kang, MD, et al. They add: “The substantial reduction in the cost of clopidogrel over the past three decades, together with the positive long-term results from the current study, warrants a reappraisal of the benefits of clopidogrel over aspirin."

“This is the first study providing a long-term comparison between the two most commonly used antiplatelet agents, and it shows a sustained benefit of clopidogrel monotherapy for lifelong secondary prevention, a finding that is particularly relevant for young patients with a long life expectancy,” write Mauro Chiarito, MD, and Francesco Tartaglia, MD, in an accompanying editorial. They add that the results may contribute to a future shift in guideline recommendations, but caution that larger RCTs in more diverse populations will be essential before clopidogrel can be definitively preferred over aspirin monotherapy.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Interventions and ACS, Interventions and Vascular Medicine

Keywords: ACC Annual Scientific Session, ACC26, New Orleans, Acute Coronary Syndrome, Clopidogrel, Drug-Eluting Stents, Ischemic Stroke, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Aspirin