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Clopidogrel or Dual Antiplatelet Therapy in High-Ischemic-Risk Patients
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?
Population
3203 high-ischemic-risk patients 12 months after drug-eluting stent implantation
Comparison
Clopidogrel monotherapy vs extended DAPT (clopidogrel + aspirin)
Design
Open-label randomized noninferiority trial in South Korea (margin 2.3 pp)
Follow-up
24 months
Authors
Discussion
Key questions
No takes yet. Share an insight, caveat, or question.
Where experts stand
Experts broadly accept noninferiority on the composite but warn that the net result masks a clinically important trade-off: clopidogrel monotherapy lowered bleeding while raising ischemic events, making de-escalation in high-risk patients a judgment call, not a default.
The headline noninferiority finding is not in dispute, but several experts caution that the composite endpoint hides opposing effects on bleeding and ischemic risk moving in opposite directions. The live question is whether individualized decision-making, potentially guided by genetic or platelet function testing, should replace blanket de-escalation in high-ischemic-risk patients.
Agreement
Multiple clinicians agree that the neutral net composite conceals clinically important opposing signals: clopidogrel monotherapy reduced bleeding but increased ischemic events, meaning the noninferiority result should not be read as simple equivalence.
3 clinicians say this directly
Main debate
Is the ischemic trade-off too steep for de-escalation, or can it be managed with individualized selection?
DAPT should continue in high-risk patients1
The ischemic price of dropping aspirin is too high unless you are willing to accept excess events to reduce minor bleeding.vs
De-escalation is viable if individualized1
Extended DAPT is not for everyone, and guided testing could improve patient selection for monotherapy.Not placed5 reporting, watching, or context only
Still unclear
Whether genetic or platelet function testing could identify patients who safely de-escalate remains untested. The relevance of a predominantly South Korean cohort to other populations, including the role of the "Asian paradox" in bleeding and ischemic balance, is unresolved. How guidelines will weigh a neutral composite that bundles opposing ischemic and bleeding signals is an open question.
Key expert perspectives
NACE is not meaningful when bleeding and ischemic signals move in opposite directions
Yeh argues that the net adverse clinical events composite is misleading here because it flattens out a real trade-off. He contends that unless clinicians are willing to accept added mortality risk to avoid minor bleeding, extended DAPT was clearly better.
Distilled from their postX post
Extended DAPT still has a role and de-escalation is not for everyone
Galli cautions against blanket de-escalation and suggests that if clopidogrel monotherapy had been guided by genetic testing or platelet function testing, the ischemic results might have looked different.
Distilled from their postX post
Active control event rate came in lower than expected, affecting trial power
Kaul points out that the observed control rate of 5.1% was well below the 7% expected, which together with the 2.3% noninferiority margin and 80% power raises questions about the trial's ability to rule out meaningful harm.
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.
Key Points
- To evaluate whether clopidogrel monotherapy is noninferior to extended dual antiplatelet therapy (DAPT) beyond 12 months after drug-eluting stent implantation in patients at high risk for ischemic events.
- Open-label, randomized noninferiority trial conducted in South Korea enrolling 3,203 patients with high-risk clinical or lesion features 12 months after drug-eluting stent placement (A-CLOSE trial, NCT03947229).
- Participants were randomly assigned 1:1 to clopidogrel monotherapy (n=1,601) or extended DAPT with clopidogrel plus aspirin (n=1,602) and followed for 24 months.
- The primary composite endpoint of net adverse clinical events occurred in 5.0% (80/1601) of the monotherapy group versus 5.1% (81/1602) of the DAPT group (risk difference, -0.1 percentage points; 90% CI, -1.3 to 1.2; P=0.001 for noninferiority, margin 2.3 percentage points).
- Key secondary ischemic events occurred in 3.7% of monotherapy vs. 1.6% of DAPT patients (HR 2.33; 95% CI, 1.47 to 3.69; P<0.001), while BARC type 2, 3, or 5 bleeding occurred in 1.8% vs. 4.1% (HR 0.43; 95% CI, 0.27 to 0.67; P<0.001).
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.
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).