Clopidogrel Versus Aspirin Monotherapy Beyond 1 Year After PCI: The Final 5-Year Results of the STOPDAPT-2 ACS and STOPDAPT-2 Total Cohort
After the first year following coronary stent treatment, clopidogrel alone lowered heart-related events versus aspirin alone without more major bleeding.
*Open-label randomized trial with blinded outcome review; Level 1b (OCEBM).
*Open-label randomized trial with blinded outcome review; Level 1b (OCEBM).
Citation
Watanabe H, Morimoto T, Natsuaki M, et al; STOPDAPT-2 ACS investigators. Clopidogrel Versus Aspirin Monotherapy Beyond 1 Year After PCI: The Final 5-Year Results of the STOPDAPT-2 ACS and STOPDAPT-2 Total Cohort. Circ Cardiovasc Interv. 2026;19:e016280. doi:10.1161/CIRCINTERVENTIONS.125.016280.
Background
After coronary stent treatment, long-term single-drug antiplatelet therapy is often continued, but the best choice remains debated. This study compared clopidogrel versus aspirin as the long-term single drug beyond 1 year.
Patients
Adults in Japan who received coronary stents; one trial enrolled only acute coronary syndrome patients. Excluded: need for long-term blood thinners and prior bleeding inside the skull.
Intervention
One month of aspirin plus a second antiplatelet drug, then clopidogrel alone long-term.
Control
Twelve months of two antiplatelet drugs, then aspirin alone long-term.
Outcome
Main outcome: combined heart-related events (heart-related death, heart attack, stroke, or definite clot in the stent) plus major/minor bleeding (trial definitions). Secondary: the heart-related composite and bleeding separately.
Follow-up Period
5 years total; primary comparison used a 1-year landmark (years 1–5).
Results
| Population (years 1–5) | Outcome | Clopidogrel | Aspirin | Relative effect | NNT |
|---|---|---|---|---|---|
| Acute coronary syndrome trial (n=2944) | Combined main outcome (primary) | 6.18% | 8.27% | Hazard ratio 0.75 (0.57–0.997) | 48 |
| Acute coronary syndrome trial (n=2944) | Heart-related composite (secondary) | 4.73% | 6.77% | Hazard ratio 0.70 (0.51–0.96) | 49 |
| Pooled trials (n=5901) | Heart-related composite (secondary) | 5.77% | 7.73% | Hazard ratio 0.74 (0.60–0.91) | 51 |
| Pooled trials (n=5901) | Heart attack | 2.15% | 3.23% | Hazard ratio 0.66 (0.48–0.92) | 93 |
| Pooled trials (n=5901) | New narrowing needing treatment outside the original stent area | 6.29% | 7.93% | Hazard ratio 0.80 (0.65–0.98) | 61 |
Analyses were primarily intention-to-treat. Major/minor bleeding rates were similar between groups.
Limitations
Open-label treatment and different antiplatelet strategies during the first year may influence later comparisons. Almost all participants were Japanese and received a specific stent type with very frequent stomach-protecting drug use, limiting generalizability.
Funding
Abbott; funder reported no role in analysis or writing.
Clinical Application
For patients stable 1 year after coronary stenting, consider clopidogrel over aspirin for long-term single therapy, especially in East-Asian populations, without expecting more major bleeding.
Journal Club
Discussion questions and an EBM quiz for this paper. How to run a journal club →
Discussion question (1)
In these open-label, adjudicator-blinded randomized trials using a 1-year landmark analysis, clopidogrel monotherapy beyond 1 year after PCI lowered the cardiovascular composite vs aspirin (e.g., 5.77% vs 7.73%; HR 0.74). Does the landmark approach/open-label design affect validity enough to change your long-term antiplatelet choice, especially outside Japan?
EBM quiz (1 question)
1. The authors compared outcomes “beyond 1 year” using a 1-year landmark analysis in a randomized trial. What is the main methodological concern with this approach?
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