Graphical abstract
Highlights
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CHET trials are abbreviated DAPT after carotid stenting in high-bleeding-risk patients.
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Randomized, multicenter design compares abbreviated DAPT→SAPT vs prolonged DAPT.
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Primary: clinically significant bleeding; secondary: net clinical ischemic/bleeding.
ABSTRACT
Rationale
Abbreviated dual antiplatelet therapy (DAPT) strategies effective in percutaneous coronary intervention among patients with high bleeding risk (HBR) may not be applicable to carotid artery stenting (CAS) owing to anatomical and procedural differences.
Primary Hypothesis
Among patients with HBR undergoing CAS, abbreviated DAPT followed by SAPT will reduce clinically significant bleeding compared to prolonged DAPT, while maintaining noninferiority in net clinical outcomes, including ischemic and major bleeding events.
Design
CHET trial is a multicenter, randomized, open-label, superiority trial in HBR patients undergoing CAS. Assuming a 38% relative reduction in bleeding (10.4%-6.45%), 1,524 participants (762 per group) provide 80% power with a two-sided alpha of 0.05; the final target is 1,556 (778 per group), allowing 2% dropout. Key HBR criteria include age ≥75 years, ischemic stroke within 6 months, renal insufficiency, anemia, and thrombocytopenia. All patients will receive aspirin and clopidogrel for 30 days after CAS (enrichment period). Event-free patients on day 30 were randomized 1:1 to receive SAPT (aspirin 100 mg daily or clopidogrel 75 mg daily, at the treating physician’s discretion) or continued DAPT for 11 months. The primary safety endpoint is clinically significant bleeding (BARC 2, 3, or 5) from day 30 to 12 months post-CAS. The secondary efficacy endpoint is a composite of nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and major bleeding (BARC 3 or 5).
Enrollment Dates and Current Status
CHET began enrollment on July 15, 2024. As of February 5, 2026, the trial is currently enrolling, with 328 participants enrolled. Enrollment is expected to be completed by November 2029, and follow-up by December 2030.
Conclusions
CHET trial is the first randomized controlled trial to define optimal DAPT duration in HBR patients after CAS.
Trial Registration
www.clinicaltrials.gov (NCT06276374).
Background
Carotid artery atherosclerotic stenosis is traditionally managed using carotid endarterectomy or pharmacotherapy. Recently, carotid artery stenting (CAS) has emerged as an important alternative. Unlike carotid endarterectomy, the cornerstone of post-CAS management is antiplatelet therapy, primarily dual antiplatelet therapy (DAPT) comprising aspirin and a P2Y12 inhibitor, such as clopidogrel, to mitigate the risk of ischemic events. , The DAPT regimen is widely recommended during the periprocedural period. However, despite its established benefits in preventing ischemic events, DAPT increases the risk of bleeding complications. ,
The optimal duration of DAPT for CAS has not been elucidated in randomized controlled trials. Current clinical practice often extrapolates recommendations from large-scale randomized controlled trials of percutaneous coronary intervention (PCI). PCI trials on DAPT duration have explored abbreviated DAPT durations (eg, 1-6 vs ≥12 months), ,, and have demonstrated the risk-reduction benefits of abbreviated DAPT, particularly in patients at high bleeding risk (HBR). Moreover, although not restricted to HBR populations, a network meta-analysis including 23 randomized controlled trials observed that de-escalation to single antiplatelet therapy after 1 to 3 months of DAPT was associated with a lower risk of bleeding without an apparent increase in stent thrombosis.
Nonetheless, direct application of PCI trial guidelines to CAS is limited owing to fundamental differences in anatomy (carotid vs coronary arteries) and the types of stents used (typically bare-metal stents in CAS vs drug-eluting stents in PCI). Current evidence of the optimal duration of DAPT after CAS derives solely from retrospective studies, which suggest that extending DAPT beyond 180 days may reduce stroke recurrence but also cause more than two-fold increase in bleeding complications. , An angioscopic study evaluating neointima formation after CAS, 19 of 20 patients demonstrated neointimal coverage at 2 months. Similarly, in stent-assisted coiling and flow diverter procedures performed in cerebral vessels, most ischemic events occurred within 30 days. Nevertheless, in a survey of 25 stroke centers in Korea that participated in this trial (Supplementary Table I), more than 60% reported the use of prolonged DAPT (duration ≥12 months) after CAS. This highlights a crucial knowledge gap regarding the optimal duration of DAPT, especially in patients with HBR who are more susceptible to the adverse effects of prolonged DAPT.
Therefore, the present study aimed to address the question of the optimal duration of DAPT with respect to its safety and efficacy.
Trial design
Study objectives and hypothesis
The primary objective of this study is to compare clinical outcomes between HBR patients who receive 1 month of DAPT followed by SAPT and those who continue DAPT for 12 months after CAS. The working hypothesis of this study is that the 1-month DAPT regimen followed by SAPT is superior to the conventional 12-month DAPT regimen in reducing clinically significant bleeding (Bleeding Academic Research Consortium [BARC] type 2, 3, or 5) from 30 days to 12 months post-CAS, while maintaining noninferiority in net clinical outcomes, defined as a composite of nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and major bleeding (BARC type 3 or 5).
Overview
The CHET trial is designed as a prospective, multicenter, randomized, open-label, clinical superiority trial. Patients will be screened exclusively at comprehensive stroke centers capable of performing CAS to determine their eligibility for trial participation. All patients with HBR, regardless of prior stroke occurrence, will be eligible for inclusion. Screening will be conducted before CAS, and informed consent will be obtained within 30 days following the procedure. After CAS, all eligible patients will receive aspirin (100 mg daily) and clopidogrel (75 mg daily) for a mandatory 30-day “enrichment period.” If a patient experiences a net clinical event during this period, they will be excluded from further participation. Patients who successfully complete the 30-day enrichment period and do not experience a net clinical event will be randomized 1:1 via a centralized, secure web-based system using permuted blocks of variable size stratified by the participating center. The allocation sequence and block sizes were concealed from the investigators to maintain allocation concealment. After randomization, patients will receive either DAPT or SAPT. Patients will undergo planned follow-up visits at 5 and 11 months after randomization (corresponding to approximately 6 and 12 months after CAS) ( Figure 1 ).
Study flow in the CHET trial.
Study population
Patients with HBR and a clinical indication for CAS will be included in this trial. Inclusion and exclusion criteria are summarized in Table .
Table
Inclusion and exclusion criteria in the CHET trial.
| Inclusion criteria | |
|---|---|
| 1 | Age ≥19 y at the time of enrollment |
| 2 | Underwent or scheduled for carotid artery stenting owing to carotid artery disease |
| 3 |
Meets one of the following NASCET-based stenosis criteria:
– Symptomatic stenosis ≥50% – Asymptomatic stenosis ≥70% |
| 4 |
Meets at least one of the following high bleeding risk criteria:
– BARC type 3 or 5 bleeding risk ≥4% per year – Intracranial hemorrhage risk ≥1% per year |
| 5 |
Specific qualifying high bleeding risk conditions (any of the following)
:
▪ Bleeding from inaccessible site (eg, GI, hematuria) within 12 mo ▪ History of unresolved BARC type 3 or 5 bleeding ▪ Age ≥75 y ▪ Thrombocytopenia <100,000/mm³ ▪ Coagulation disorders (eg, vWD, factor deficiencies) ▪ Hemoglobin level of <12 g/dL in males and <11 g/dL in females, or having received a blood transfusion within the past 4 wk ▪ Active malignancy (excluding nonmelanoma skin cancer) ▪ Renal disease (dialysis, transplant, or eGFR < 60 mL/min/1.73 m²) ▪ Liver disease (cirrhosis with portal hypertension) ▪ Cerebral microbleeds ≥5 ▪ Ischemic stroke or transient ischemic attack within 6 mo ▪ History of spontaneous (nontraumatic) intracranial hemorrhage at any time, or traumatic intracranial hemorrhage within 12 mo |
| Exclusion criteria | |
| 1 | Net clinical event (eg, cardiovascular event or major bleeding) occurring within 30 d after CAS |
| 2 |
Discontinuation of DAPT within 30 d post-CAS
※ Temporary interruption (≤7 d) is allowed if resumed between d 20 and 30 |
| 3 | History of other stent implantation or revascularization surgery (eg, CABG) requiring DAPT within past 12 mo |
| 4 | Known hypersensitivity to aspirin or clopidogrel |
| 5 | Pregnant or lactating women |
| 6 | Need for anticoagulation therapy for >12 mo |
| 7 | Requirement for antiplatelet agents not specified in the study protocol |
| 8 | Participation in another interventional clinical trial |
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