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Clopidogrel or Dual Antiplatelet Therapy in High-Ischemic-Risk Patients
Byeong-Keuk KimSeung-Jun LeeYong-Joon LeeKyounghoon LeeDeok‐Kyu ChoYun‐Hyeong ChoSung Gyun AhnKyeong Ho YunJi-Yong JangSeunghwan KimYong Hoon KimYong Hwan ParkSung Uk KwonSeung‐Ho HurTae Soo KangEun‐Seok ShinJin Bae LeeKi‐Hyun JeonUng KimWon–Ho KimBum‐Kee HongSang‐Hyup LeeSung-Jin HongChul‐Min AhnJung‐Sun KimYoung-Guk KoDonghoon ChoiMyeong-Ki HongYangsoo Jang
Key result
Clopidogrel monotherapy proves noninferior to extended DAPT for net adverse clinical events in high-risk patients.
- risk difference -0.1 percentage points
- 95% CI -1.3 to 1.2
- P=0.001 for noninferiority
- n=3,203
Why the trial?
After high-risk PCI, extended dual antiplatelet therapy lowers ischaemic risk at the price of bleeding. Whether clopidogrel monotherapy can preserve ischaemic protection while reducing bleeding in this high-risk population had not been established.
Does clopidogrel monotherapy compared with extended DAPT improve net adverse clinical events in high-ischemic-risk patients 12 months after drug-eluting stent implantation?
Evidence details
What drove the result?
| Outcome | Clopidogrel | DAPT |
|---|---|---|
| Net adverse clinical events (death, MI, ST, stroke, BARC 2/3/5) | 80 (5.0%) | 81 (5.1%) |
| Risk difference -0.1 pp (90% CI -1.3 to 1.2); P=0.001 for noninferiority | ||
| Death, MI, stent thrombosis, or stroke | 60 (3.7%) | 26 (1.6%) |
| Key secondary - higher with monotherapy (HR 2.33, 1.47-3.69; P<0.001); opposite direction from bleeding | ||
Limitations & tradeoffs
Safety
BARC 2, 3, or 5 bleeding 28 (1.8%) vs 65 (4.1%); HR 0.43 (95% CI 0.27-0.67); P<0.001.
Design limitations
open-label design, and the net composite balances ischemic and bleeding events that moved in opposite directions, so the neutral net result masks trade-offs.
Representation
conducted only in South Korea, which may limit generalizability.
Structured PICO
Does clopidogrel monotherapy compared with extended DAPT improve net adverse clinical events in high-ischemic-risk patients 12 months after drug-eluting stent implantation?
P
Population
3,203 patients with high-risk clinical or lesion characteristics 12 months after drug-eluting stent implantation, followed for 24 months.
I
Intervention
Clopidogrel monotherapy
C
Comparator
Extended dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin
O
Outcome
Net adverse clinical events, a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, or Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 24 monthscomposite
Main Result
Effect estimate: risk difference -0.1 percentage points (95% CI -1.3 to 1.2)
Absolute Event Rate: 5% vs 5.1%
p-value: p=0.001 for noninferiority
Clopidogrel monotherapy was noninferior to extended DAPT for net adverse clinical events at 24 months in high-risk patients 12 months post-DES, driven by reduced bleeding despite increased ischemic events.
Discussion
Key questions
No takes yet. Share an insight, caveat, or question.
Where experts stand
Experts read A-CLOSE as a technically positive noninferiority result that masks a clinically important tradeoff: clopidogrel monotherapy reduced bleeding but increased ischemic events, leaving most cautious about routine de-escalation in high-risk patients.
The net composite endpoint met noninferiority, but cardiologists are focused on the diverging components: less bleeding with monotherapy came at the cost of more ischemic events. Several experts argue that a neutral composite can hide opposing signals that matter differently to patients. The live question is whether extended DAPT should remain standard for high-ischemic-risk patients or whether guided de-escalation using genetic or platelet function testing could thread the needle.
Agreement
Multiple experts warn that the neutral net composite conceals clinically meaningful opposing signals, with bleeding going down and ischemic events going up under clopidogrel monotherapy. They argue the headline noninferiority finding should not be taken at face value.
3 clinicians say this directly
Main debate
Drop aspirin after 12 months vs. keep extended DAPT for high-risk patients
Monotherapy viable after 12 event-free months1
The composite was noninferior and the bleeding reduction with monotherapy is a meaningful benefit for stable patients.vs
Extended DAPT still needed for high ischemic risk2
The ischemic signal with monotherapy is too large to accept in exchange for less minor bleeding, and de-escalation should not be routine.+2Not placed7 reporting, watching, or context only
Still unclear
Whether guided de-escalation using genetic testing or platelet function testing could identify patients who safely benefit from monotherapy remains untested. The role of the "Asian paradox" in these findings, raised by at least one expert, is unresolved. How guideline committees will weigh the opposing ischemic and bleeding signals is still an open question.
Key expert perspectives
AJACC Journal Scan
“Extended DAPT provided greater protection against major ischemic events, including death, whereas clopidogrel monotherapy reduced major or clinically relevant bleeding. It seems that no single strategy is best for every patient, but rather, long-term antiplatelet therapy should be individualized...”
NACE is not meaningful when bleeding and ischemic risks move in opposite directions
Argues that the net adverse clinical events composite obscures the real tradeoff. Unless clinicians are willing to accept mortality risk to avoid minor bleeding, DAPT was clearly the better strategy in this population.
Distilled from their postX post
Extended DAPT still has a role and de-escalation is not for everyone
Reads the result as evidence that routine de-escalation is inappropriate. Suggests that if clopidogrel monotherapy were guided by genetic testing or platelet function testing, the results might have been different.
Distilled from their postX post
Implication
May support switching to clopidogrel monotherapy after 12 months to reduce bleeding; extends randomized evidence on DAPT de-escalation in high-ischemic-risk patients.
Abstract
BackgroundThe effect of clopidogrel monotherapy as compared with extended dual antiplatelet therapy (DAPT) with clopidogrel and aspirin beyond 12 months after implantation of a drug-eluting stent remains uncertain in patients at high risk for recurrent ischemic events. MethodsIn this open-label noninferiority trial conducted in South Korea, we enrolled patients with high-risk clinical or lesion characteristics in whom a drug-eluting stent had been implanted 12 months earlier and randomly assigned them, in a 1:1 ratio, to receive clopidogrel monotherapy or extended DAPT (clopidogrel plus aspirin). The primary end point was net adverse clinical events, a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, or Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 24 months (noninferiority margin, 2.3 percentage points). Key secondary ischemic and bleeding end points were tested in a prespecified hierarchical order. ResultsOf the 3203 patients who underwent randomization, 1601 were assigned to receive clopidogrel monotherapy and 1602 to receive extended DAPT. Over the course of 24 months, a primary end-point event occurred in 80 patients (5.0%) in the monotherapy group and in 81 (5.1%) in the DAPT group (risk difference, −0.1 percentage points; 90% confidence interval [CI], −1.3 to 1.2; P=0.001 for noninferiority). Death from any cause, myocardial infarction, stent thrombosis, or stroke (the key secondary ischemic end point) occurred in 60 patients (3.7%) in the monotherapy group and in 26 (1.6%) in the DAPT group (hazard ratio, 2.33; 95% CI, 1.47 to 3.69; P<0.001). BARC type 2, 3, or 5 bleeding (the key secondary bleeding end point) occurred in 28 patients (1.8%) in the monotherapy group and in 65 (4.1%) in the DAPT group (hazard ratio, 0.43; 95% CI, 0.27 to 0.67; P<0.001). The incidence of serious adverse events was similar in the two groups. ConclusionsAmong patients at high risk for ischemic events 12 months after drug-eluting stent implantation, clopidogrel monotherapy was noninferior to extended DAPT with respect to net adverse clinical events at 24 months. (Funded by Chong Kun Dang and Samjin; A-CLOSE ClinicalTrials.gov number, NCT03947229.)
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Lee et al. (2026) conducted an RCT in High risk for recurrent ischemic events after drug-eluting stent implantation (n=3,203). Clopidogrel monotherapy vs. Extended DAPT (clopidogrel plus aspirin) was evaluated on Net adverse clinical events, a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, or Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 24 months (risk difference -0.1 percentage points, 95% CI -1.3 to 1.2, p=0.001 for noninferiority). Clopidogrel monotherapy was noninferior to extended DAPT for net adverse clinical events at 24 months (5.0% vs 5.1%; risk difference -0.1 percentage points; P=0.001 for noninferiority).