Update to Chapter 39: Evaluation and Management of Non-ST-Segment Elevation Myocardial Infarction, Chapter 40: ST-Segment Elevation Myocardial Infarction, Chapter 42: Percutaneous Coronary Interventions in Acute Myocardial Infarction and Acute Coronary Syndromes, Chapter 43: The Evaluation and Management of Stable Ischemic Heart Disease and Chapter 44: Coronary Artery Bypass Grafting and Percutaneous Interventions in Stable Ischemic Heart Disease

Study Summary

The optimal antiplatelet monotherapy during the chronic maintenance period long after coronary stenting is unclear. The HOST-EXAM trial was conducted in South Korea and enrolled 5530 patients who maintained dual antiplatelet therapy (DAPT) without clinical events for 6-18 months following percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Patients were randomized 1:1 to receive clopidogrel 75 mg once daily (n=2710) or aspirin 100 mg once daily (n=2728) for 24 months.  The median time from PCI to randomization was 382 days (IQR 357-422). The primary end point was the composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater. The primary outcome occurred in 152 (5.7%) patients in the clopidogrel group and in 207 (7.7%) patients in the aspirin group (HR 0.73, 95% CI 0.59-0.90; P = 0.0035; see accompanying Hurst’s Central Illustration). The benefit of clopidogrel monotherapy was observed in both thrombotic (3.7% versus 5.5%; P = 0.003) and bleeding end points (2.3% versus 3.3%; P=0.036), and the results were consistent across major patient subgroups, including baseline P2Y₁₂ inhibitor and time from index PCI (<365 versus ≥365 days).

Commentary

Study Strengths: This is a large contemporary randomized trial to compare the effectiveness of two types of antiplatelet monotherapy at long-term administration following PCI with DES. The study largely confirms the CAPRIE trial which had showed that clopidogrel was more effective than aspirin in reducing cardiovascular adverse events in nearly 20,000 patients with cerebrovascular, coronary, or peripheral arterial disease. However, HOST-EXAM focused on a contemporary PCI population treated with DES.

Study Limitations: The open-label design had a potential for bias in outcome reporting and ascertainment, hence all events were adjudicated by a blinded committee. Phenotypic and genetic testing for clopidogrel was not done although the study population was East Asian (previously reported to have high rates of clopidogrel resistance). Despite this, multiple studies have shown lower thrombotic event rates in this group, a phenomenon termed the east Asian paradox. The clinical impact of clopidogrel resistance among east Asians, including the possibility of lower bleeding rates, limits the generalizability of this study. Considering that maintenance antiplatelet therapy may be clinically interpreted as ‘indefinite,’ the follow-up duration of 2 years might be too short to give a concrete conclusion.

Next Steps/Clinical Perspective: Current practice guidelines recommend a period of DAPT after PCI to prevent immediate complications, followed by antiplatelet monotherapy during the chronic maintenance phase for secondary prevention. Aspirin has generally been assumed for this purpose. However, this well-executed trial has the potential to change current clinical practice. The generalizability and cost-effectiveness of clopidogrel remain dubious. The HOST-EXAM Extended Study will prolong the median follow-up to 10 years to further study chronic maintenance monotherapy with clopidogrel.

Trial Reference