Long-Term Cardiovascular Care: 10-Year Data Challenge Aspirin’s Role in Post-Stent Maintenance

In a major shift for cardiovascular medicine, the final 10-year follow-up results of the HOST-EXAM (NCT02044250) trial have demonstrated that clopidogrel (Plavix; Bristol Myers Squibb) monotherapy is superior to aspirin for long-term maintenance in patients who have undergone percutaneous coronary intervention (PCI). The results, published and presented as a late-breaking clinical trial at the American College of Cardiology 2026 Scientific Sessions, provide the longest randomized comparison of antiplatelet monotherapy to date, suggesting a shift in the decades-old standard of lifelong aspirin therapy.¹

A Decade of Data: The HOST-EXAM Findings

The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of coronary artery diseases – EXtended Antiplatelet Monotherapy) trial initially enrolled 5530 patients across 37 centers in South Korea. These patients had successfully completed an initial 6 to 18 months of dual antiplatelet therapy without clinical events following a PCI with drug-eluting stents. They were then randomized to receive either clopidogrel (75 mg once daily) or aspirin (100 mg once daily) as lifelong maintenance therapy.²

After a median follow-up of 10.5 years, the study found that clopidogrel significantly reduced the risk of the primary composite end point—a net clinical outcome including all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding. The primary end point occurred in 25.4% of the clopidogrel group compared to 28.5% of the aspirin group (hazard ratio 0.86; P = .0050).^1,2

Crucially, the benefit of clopidogrel was biphasic, meaning it simultaneously reduced both thrombotic and bleeding risks. The thrombotic composite end point was lower in the clopidogrel group (17.3% versus 20.0%), as was the rate of any bleeding (9.1% versus 10.8%). However, the researchers noted that all-cause mortality remained similar between the 2 groups (13.4% for clopidogrel versus 12.5% for aspirin), suggesting that while clopidogrel prevents non-fatal events, it may not alter overall survival in this chronic phase.^1,2

The Cumulative Benefit and Adherence

One of the most striking aspects of the 10-year data is the decreasing number needed to treat clopidogrel (NNT) over time. At the 2-year mark, the NNT to prevent 1 primary event was 51; by 5 years, it dropped to 24; and at the 10-year mark, it reached 33 in the intention-to-treat analysis and 17 in the per-protocol analysis. This indicates that the clinical benefit of clopidogrel is cumulative, growing more significant the longer the patient remains on the therapy.^1,2

Furthermore, the trial highlighted a significant difference in patient tolerability. Adherence was notably higher in the clopidogrel group (78.9%) than in the aspirin group (74.8%). The primary reasons for discontinuing aspirin were gastrointestinal (GI) discomfort and minor bleeding, common adverse effects that can lead patients to stop their medication without consulting a physician.²

Why This Matters to Pharmacists

For pharmacists, the HOST-EXAM 10-year data are highly relevant, as they serve as the primary gatekeepers of medication therapy management (MTM) and patient counseling. Pharmacists are often the first to hear about adverse effects like dyspepsia or minor bruising. Knowing that clopidogrel has better long-term adherence and fewer GI complications than aspirin allows pharmacists to provide evidence-based recommendations to both patients and providers.

Current 2024 European guidelines already give clopidogrel a Class I, Level A recommendation for long-term maintenance based on intermediate data.³ Pharmacists must stay abreast of these changes to ensure patients are on the most effective secondary prevention therapy.

Given that the average age for PCI is around 60, these patients may require therapy for 20 years or more. The HOST-EXAM data confirms that the choice of monotherapy has a decades-long impact on a patient’s risk profile. However, presenter Hyo-Soo Kim, PhD, professor in the Department of Internal Medicine at Seoul National University College of Medicine, noted clinicians should be aware that patients in East Asia have a high prevalence of CYP2C19 loss-of-function alleles (affecting clopidogrel metabolism) but actually experience lower thrombotic rates than Western populations. Although the trial was conducted in South Korea, limiting generalizability to other ethnicities, the robust 10-year results suggest clopidogrel’s efficacy remains high even in this unique genetic context.^1,2

The HOST-EXAM 10Y results suggest that the era of aspirin as the sacrosanct first-line agent for lifelong post-PCI care may be coming to an end. As clopidogrel is now widely accessible and inexpensive, it represents a potent, better-tolerated alternative that offers a cumulative shield against both clotting and bleeding over the long haul.

REFERENCES

1. Kim HS. 10-year follow-up of clopidogrel vs aspirin monotherapy in stable coronary artery disease after percutaneous coronary intervention with drug-eluting stent. Presented at: American College of Cardiology 2026 Scientific Sessions. March 29, 2026; New Orleans, LA.

2. Kang J, Park S, Yang HM, et al. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention: 10-year follow-up of the HOST-EXAM trial. The Lancet. March 29, 2026. doi:10.1016/S0140-6736(26)00422-8

3. Galli M, Gragnano F, Vrints C, Andreotti F. 2024 ESC guidelines on chronic coronary syndromes: what is new in pharmacotherapy? Eur Heart J – Cardiovasc Pharmacother. 2024;10(7):572-574. doi:10.1093/ehjcvp/pvae069