HOST-EXAM: Clopidogrel Bests Aspirin for Long-Term Antiplatelet Following PCI

Kyung Woo Park, MD, PhD

Credit: Seoul National University College of Medicine

Data from a post hoc analysis of the HOST-EXAM trial suggest clopidogrel monotherapy was associated with a lower rate of adverse events following coronary artery stenting among people with and without diabetes compared to aspirin use.¹

Results of the study, which included more than 5400 people, suggests people with diabetes using clopidogrel after percutaneous coronary intervention (PCI) had a 31% lower risk of the trial’s primary composite endpoint of all-cause death, nonfatal myocardial infarction (MI), stroke, readmission due to acute coronary syndrome, and major bleeding at 24-month follow-up relative to those using aspirin.¹

“In this post hoc analysis of the HOST-EXAM randomized clinical trial, clopidogrel monotherapy was associated with a lower risk of the primary composite end point in both patients with and without diabetes,” wrote investigators.¹ “These results may inform decision making for long-term therapy following PCI.”

An investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea, the Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis–Extended Antiplatelet Monotherapy (HOST-EXAM) was conducted from March 2014-May 2018 and enrolled 5438 patients who maintained dual anti platelet therapy without clinical events for 6-18 months after PCI with drug-eluting stents. These patients were randomized in a 1:1 ratio to receive 75 mg clopidogrel once-daily or 100 mg aspirin once-daily.²

Initial results of the HOST-EXAM trial concluded use of clopidogrel was associated with a 26% relative reduction in risk of the trial’s primary composite endpoint and a 26% lower risk of major bleeding events.²

The primary outcome of interest for the trial was a composite endpoint of all-cause death, nonfatal MI, stroke, readmission attributable to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) type 3 or greater bleeding. The trial included a secondary thrombotic endpoint, which was a composite of cardiac death, nonfatal MI, ischemic stroke, readmission attributable to acute coronary syndrome, and definite or probable stent thrombosis, and a bleeding endpoint, which was defined as BARC type 2 or greater bleeding.¹

The overall study cohort had a mean age of 63.5 (SD, 10.7) years and 25.5% were female. Of the 5438 patients enrolled in the trial, 34.2% (n=1860) had diabetes. Investigators noted 98.2% of participants completed the 24-month follow-up.¹

Results of the investigators’ analyses suggested the rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69 [95% confidence interval [CI], 0.49-0.96]; P=.03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3%vs 7.0%; HR, 0.76 [95% CI, 0.58-1.00]; P=.046; ARD, 1.6%; NNT, 63; P for interaction = .65). Investigators pointed out results suggested diabetes was not associated with a difference in benefit observed with use of clopidogrel monotherapy relative to aspirin for the thrombotic composite endpoint (HR, 0.68 [95% CI, 0.45-1.04] for patients with diabetes vs HR, 0.68 [95% CI, 0.49-0.93] for those without; P for interaction = .99) and any bleeding with BARC 2, 4, or 5 (HR, 0.65 [95% CI, 0.39-1.09] for patients with diabetes vs HR, 0.74 [95% CI, 0.48-1.13] for those without; P for interaction=.71).¹

“The results of our study suggest that clopidogrel could be considered over aspirin for long-term maintenance antiplatelet therapy after PCI in both patients with and without diabetes,” wrote investigators.¹ “Although not significant due to insufficient statistical power in each group, the association of clopidogrel with reduced risk compared with aspirin was consistent for both thrombotic and bleeding outcomes in both the diabetes and no diabetes groups.”

References

1. Rhee TM, Bae JW, Park KW, et al. Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the HOST-EXAM Trial [published online ahead of print, 2023 Apr 12]. JAMA Cardiol. 2023;10.1001/jamacardio.2023.0592. doi:10.1001/jamacardio.2023.0592
2. Kang J, Park KW, Lee H, et al. Aspirin Versus Clopidogrel for Long-Term Maintenance Monotherapy After Percutaneous Coronary Intervention: The HOST-EXAM Extended Study. Circulation. 2023;147(2):108-117. doi:10.1161/CIRCULATIONAHA.122.062770