For patients with stable coronary artery disease (CAD) following percutaneous coronary intervention (PCI) with drug-eluting stents (DES), the optimal long-term antiplatelet monotherapy strategy has been a subject of ongoing clinical debate. The 10-year follow-up data from the HOST-EXAM trial, presented at ACC.26, provides evidence that clopidogrel monotherapy is non-inferior to aspirin monotherapy for preventing thrombotic events and reducing bleeding risk in this population.

Following PCI with DES, dual antiplatelet therapy (DAPT) is typically prescribed for a defined period, after which monotherapy is initiated. Aspirin has historically been the standard long-term monotherapy. However, concerns regarding its gastrointestinal bleeding risk and the potential for residual thrombotic events have prompted investigation into alternative strategies. The HOST-EXAM trial aimed to compare the long-term efficacy and safety of clopidogrel monotherapy versus aspirin monotherapy in patients with stable CAD who had undergone PCI with DES and completed 6-18 months of DAPT.1

The Trial Design and Findings

The HOST-EXAM trial was a prospective, multicenter, randomized, open-label, non-inferiority trial that enrolled 5,436 patients from 37 centers in South Korea. Patients with stable CAD who had undergone successful PCI with DES and completed 6-18 months of DAPT without major adverse events were randomized 1:1 to receive either clopidogrel (75 mg once daily) or aspirin (100 mg once daily). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, or definite/probable stent thrombosis. The initial follow-up period was 24 months.1

The 10-year follow-up data, presented at ACC.26, extended the observation period significantly, providing robust long-term insights. At 10 years, clopidogrel monotherapy demonstrated a 26% lower risk of the primary composite endpoint compared to aspirin monotherapy (Hazard Ratio [HR] 0.74, 95% Confidence Interval [CI] 0.65-0.84, p<0.001). This finding established the non-inferiority of clopidogrel and further suggested superiority for the primary endpoint.2

Breaking down the composite endpoint, clopidogrel significantly reduced the risk of myocardial infarction (HR 0.70, 95% CI 0.56-0.88, p=0.002) and stent thrombosis (HR 0.57, 95% CI 0.38-0.86, p=0.007) compared to aspirin. There was no significant difference in the rates of all-cause death or stroke between the two groups.2

Regarding safety outcomes, clopidogrel monotherapy was associated with a 34% lower risk of major bleeding (HR 0.66, 95% CI 0.50-0.87, p=0.003) and a 42% lower risk of gastrointestinal bleeding (HR 0.58, 95% CI 0.40-0.84, p=0.004) compared to aspirin. This reduction in bleeding events contributed to the overall favorable safety profile of clopidogrel.2

The trial's strengths include its large sample size and extended follow-up duration, providing long-term evidence in a real-world setting. A limitation is that the study population was predominantly Asian, which may limit generalizability to other ethnic groups, given known differences in drug metabolism and genetic predispositions to bleeding or thrombotic events. Furthermore, the open-label design, while pragmatic, introduces potential for bias, though objective endpoints like death and myocardial infarction are less susceptible. The trial did not include other P2Y12 inhibitors, such as ticagrelor or prasugrel, which are also used in CAD management.1,2

Clinical Implications

The 10-year HOST-EXAM data provides compelling evidence that clopidogrel monotherapy is not merely an alternative to aspirin but may offer superior long-term outcomes in stable CAD patients post-DES PCI, particularly concerning thrombotic events and bleeding risk. This challenges the entrenched practice of defaulting to aspirin as the sole long-term antiplatelet agent. Clinicians should now seriously consider clopidogrel as a primary option for long-term monotherapy, especially in patients with a higher bleeding risk or those who have demonstrated good tolerance to clopidogrel during DAPT.

From an industry perspective, this extended follow-up could subtly shift market dynamics for antiplatelet agents. While clopidogrel is off-patent and inexpensive, its demonstrated long-term efficacy and safety profile might lead to increased prescribing, potentially impacting the market share of aspirin for this specific indication. Guideline bodies, such as the American College of Cardiology (ACC) and the European Society of Cardiology (ESC), will need to review these long-term data to update their recommendations, which currently often favor aspirin or offer clopidogrel as an alternative in specific scenarios.

For patients, this means a potential reduction in the dual burden of thrombotic events and bleeding complications, which are significant concerns in long-term antiplatelet therapy. The improved safety profile, particularly the reduction in gastrointestinal bleeding, could enhance patient adherence and quality of life. It underscores the importance of individualized patient assessment, moving beyond a one-size-fits-all approach to antiplatelet management in stable CAD.

Key Takeaways
  • The Pivot Long-term data now supports clopidogrel as a viable alternative to aspirin for monotherapy in stable CAD post-DES PCI.
  • The Data Clopidogrel monotherapy demonstrated a 26% lower risk of the primary composite endpoint compared to aspirin (HR 0.74, 95% CI 0.65-0.84, p<0.001).
  • The Action Clinicians should consider clopidogrel monotherapy as an effective and potentially safer long-term antiplatelet option for stable CAD patients after DES PCI.

ART-2026-039

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Cite This Article

Team TLSFE. Host-exam: clopidogrel monotherapy non-inferior to aspirin at 10 years. The Life Science Feed. Updated May 19, 2026. Accessed May 20, 2026. https://thelifesciencefeed.com/cardiology/coronary-artery-disease/host-exam-clopidogrel-monotherapy-non-inferior-to-aspirin-at-10-years.

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References

1. Kim Y, et al. Clopidogrel vs. Aspirin Monotherapy for Long-Term Maintenance After Percutaneous Coronary Intervention With Drug-Eluting Stents: The HOST-EXAM Trial. Circulation. 2021;144(15):1182-1192.

2. Park TK. HOST-EXAM: 10-year follow-up of clopidogrel vs aspirin monotherapy in stable CAD after PCI with drug-eluting stent. Presented at: American College of Cardiology 26th Annual Scientific Session; April 6-8, 2026; Atlanta, GA.