Key Points:
- After percutaneous coronary intervention (PCI), following an initial period of dual antiplatelet therapy (DAPT)., guidelines recommend lifelong single antiplatelet therapy (SAPT). While aspirin has traditionally been the standard agent, recent trials and meta-analyses have suggested that clopidogrel monotherapy may be superior to aspirin in this setting. However, no randomized trial had previously assessed antiplatelet monotherapy beyond 5 years after PCI.
- The HOST-EXAM trial randomized 5,438 patients in South Korea who had undergone PCI with drug-eluting stents and completed 6–18 months of DAPT without clinical events to clopidogrel 75 mg daily or aspirin 100 mg daily. This prespecified 10-year extended follow-up provides the longest randomized comparison of antiplatelet monotherapy after PCI.
- At a median follow-up of 10.5 years, clopidogrel was associated with a significantly lower rate of the primary composite endpoint compared with aspirin. The cumulative benefit of clopidogrel increased over time, with the number needed to treat decreasing from 51 at 2 years to 33 at 10 years. Clopidogrel was also superior for the thrombotic composite endpoint and bleeding of any kind. There was no significant difference in all-cause death between the groups.
- These findings provide the longest randomized evidence to date supporting clopidogrel over aspirin for chronic antiplatelet monotherapy after PCI.
Antiplatelet monotherapy is a cornerstone of secondary prevention after PCI and is generally continued indefinitely after completion of DAPT. Aspirin has historically been the default agent, however, the potential superiority of clopidogrel over aspirin was first suggested by the CAPRIE trial and has been reinforced by the original HOST EXAM trial and the SMART- CHOICE 3SMART-CHOICE 3 trial, which demonstrated lower rates of cardiovascular events with clopidogrel. Despite these findings, the longest available randomized follow-up comparing these agents was approximately 5 years. Given that secondary prevention is required indefinitely, longer-term data are needed.
On March 29th 2026, the results of the “10-Year Follow-Up of Clopidogrel Versus Aspirin Monotherapy in Stable Coronary Artery Disease After Percutaneous Coronary Intervention with Drug-Eluting Stent (HOST-EXAM 10Y)” were presented at ACC Scientific Sessions 2026, with simultaneous publication in The Lancet. The purpose of this prespecified extended follow-up was to evaluate thelong-term comparative effects of clopidogrel versus aspirin monotherapy during the chronic maintenance phase after PCI.
HOST-EXAM was an investigator-initiated, prospective, randomized, open-label, multicenter trial conducted at 37 sites in South Korea [NCT02044250]. Patients aged 20 years or older who underwent PCI with drug-eluting stents and maintained DAPT without any clinical events for 6–18 months after PCI were eligible for enrollment. Patients were randomized in a 1:1 ratio to receive clopidogrel 75 mg once daily or aspirin 100 mg once daily. The randomized antiplatelet strategy was mandated during the initial 24-month in-trial period, after which antiplatelet therapy was at the discretion of the treating physician. Clinical follow-up was scheduled annually for up to 10 years. The primary endpoint was a “patient-oriented composite outomce” of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome (ACS), and major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3. Secondary endpoints included a thrombotic composite (cardiovascular death, non-fatal MI, ischemic stroke, readmission due to ACS, and stent thrombosis) and any bleeding (BARC type ≥2). The primary analysis was performed in the intention-to-treat population.
From March 2014 through May 2018, 5,530 patients were screnned, of whom 5,438 were successfully randomized: 2,710 to clopidogrel and 2,728 to aspirin. The median age was 64 years, 74.6% were male, and 34.2% had diabetes. Approximately 72% had presented with ACS at the time of their index PCI, including 17% with STEMI. Clinical and angiographic characteristics were well balanced between groups. Loss to follow up was minimal, with outcome ascertainment achieved in 92.8% of patients at a median follow-up of 10.5 years (IQR 9.4–11.4) after PCI.
The primary composite endpoint occurred in 646 patients (25.4%) in the clopidogrel group and 739 patients (28.5%) in the aspirin group (HR 0.86 [95% CI: 0.77–0.96]; p=0.005), with a number needed to treat of 33 to prevent one primary endpoint event. The thrombotic composite endpoint occurred in 17.3% of the clopidogrel group versus 20.0% of the aspirin group (HR 0.82 [95% CI: 0.72–0.93]; p=0.002), driven primarily by lower rates of stroke (4.6% vs. 6.4%; HR 0.72 [95% CI: 0.56–0.92]; p=0.008) and readmission due to ACS (8.7% vs. 11.0%; HR 0.75 [95% CI: 0.63–0.90]; p=0.002). Any bleeding (BARC type ≥2) was also lower with clopidogrel (9.1% vs. 10.8%; HR 0.81 [95% CI: 0.68–0.97]; p=0.020), driven primarily by lower rates of BARC type 3 major bleeding (5.6% vs. 7.7%; HR 0.71 [95% CI: 0.57–0.88]; p=0.002). There was no significant difference in all-cause death between the two groups (13.4% vs. 12.5%; HR 1.07 [95% CI: 0.92–1.24]; p=0.40). Results were generally consistent across prespecified subgroups, with a significant interaction observed for chronic kidney disease, favoring greater benefit with clopidogrel in this subgroup. Notably, the number needed to treat decreased progressively from 45 at 2 years, to 24 at 5 years, to 17 at 10 years in the per-protocol analysis, underscoring the cumulative nature of the benefit of clopidogrel over aspirin.
In a per-protocol analysis of the 4,179 patients who adhered to their assigned medication throughout follow-up, the treatment effect of clopidogrel was more pronounced for the primary composite endpoint (24.0% vs. 29.8%; HR 0.76 [95% CI: 0.67–0.86]; p<0.0001), with a number needed to treat of ~17. Similarly, clopidogrel was superior to aspirin for both the thrombotic and bleeding outcome in this analysis. Adherence to the allocated medication was higher in the clopidogrel group (78.9%) than the aspirin group (74.8%; p<0.0004), with gastrointestinal discomfort and minor bleeding being more common reasons for discontinuation in the aspirin group.
Limitations include the fact that this was an extended follow-up of a randomized trial in which no antiplatelet regimen was mandated after the initial 2-year trial period; physician discretion in antiplatelet selection during the post-trial period could have influenced outcomes. Second, the trial was conducted exclusively in an East Asian population, which may limit generalizability, particularly given the high prevalence of CYP2C19 loss-of-function alleles and the routine use of imaging-guided PCI in this region. Whether the results are influenced by clopidogrel metabolizer status remains unknown. Third, the open-label design could introduce bias in the adjudication of certain endpoints, such as readmission due to ACS, although all events were adjudicated by an independent clinical events committee and the majority of ACS readmissions required urgent revascularization. Fourth, women were under-represented at 25.4% of the study population. Finally, adjustment for multiple testing across secondary endpoints was not performed. Data on temporary discontinuation (e.g. for procedures) was not collected.
Hyo-Soo Kim, MD, PhD, of the Biomedical Research Institute at Seoul National University Hospital in Seoul, South Korea, concluded: “In patients who received PCI with a drug-eluting stent and were event-free under DAPT for 6 to 18 months after PCI, clopidogrel monotherapy as compared with aspirin monotherapy significantly reduced the risk of the composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to ACS, and major bleeding over a 10-year follow-up period. The beneficial effect of clopidogrel was observed in both thrombotic and bleeding endpoints. Clopidogrel may be considered as the preferred agent for long-term antiplatelet monotherapy during the chronic maintenance phase after PCI.”