Why is this study important?

• The HOST-EXAM trial compared clopidogrel to aspirin used as maintenance monotherapy in patients who had undergone percutaneous coronary intervention (PCI) after completing 6 -18 months of event-free dual antiplatelet therapy.
• The study demonstrated superiority of clopidogrel when comparing the composite endpoint of bleeding and clotting events (cardiovascular death, MI, stroke, ACS readmission, stent thrombosis) at two years. The benefits were found to be sustained out to a median of 5.8 years.
• Previously published results had not differentiated outcomes of patients who had undergone PCI for acute coronary syndrome (ACS) and non-ACS
• Results of the post-hoc subgroup analysis classifying the outcomes of ACS and non-ACS patients were presented at the Cardiovascular Research Technologies (CRT) 2023 in Washington, D.C.

What did the study show?

• Patient-oriented composite outcome (POCO): a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to ACS and major bleeding complications was used as the primary endpoint.
• In the ACS subgroup, 1,964 patients took clopidogrel and 1,957 took aspirin as chronic monotherapy. Statistically significant lower POCO was observed with clopidogrel as compared to aspirin (13.7% vs. 17.7%; hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.66-0.92; log-rank p=0.003).
• In the non-ACS subgroup, clopidogrel monotherapy resulted in a lower POCO rate when compared to aspirin. However, the difference was not statistically significant (14.8% vs. 18.2%; HR: 0.82; 95% CI: 0.63-1.06; log-rank p=0.100).
• Thrombotic outcomes were lower in the ACS sub-group and bleeding outcomes lower in the non-ACS subgroup in patients receiving clopidogrel.

Key Takeaways

• Among patients presenting with CAD undergoing PCI who maintained dual antiplatelet therapy without any ischemic or major bleeding events for 6-18 months after PCI, the beneficial effect of clopidogrel monotherapy over aspirin monotherapy was observed in both the ACS and non-ACS subgroups. The primary composite outcome was statistically significant in the ACS subgroup.
• The study does have limitations. The results represent a post-hoc analysis of a study not originally designed and powered to compare the difference in the two subgroups. Also, the study population was entirely East Asian, a population subgroup who are known to have a different response to antiplatelet therapy when compared to other geographical and ethnic subgroups. The outcomes seen in this subgroup may not apply to other populations.
• With the plethora of recent data on the benefits of shorter duration of DAPT in ACS with the newer P2Y12 inhibitors, this study reintroduces clopidogrel monotherapy in a new role as a potentially viable standalone agent for chronic monotherapy after DAPT in patients undergoing PCI. 

All editors: Yuvraj Chowdhury, MD