Drug-Coated Balloon Versus Drug-Eluting Stent for Treatment of De-Novo Coronary Lesions in Patients With High Bleeding Risk-2

Official title

Discontinuation of Antiplatelet Agent After Drug-Coated Balloon Angioplasty in Stabilized Patients With High Bleeding Risk and Coronary Artery Disease

Overview

A prospective, multi-center, open-label, randomized controlled, and superiority trial. The trial will compare clinical outcomes between discontinuation of antiplatelet agent and continuation of antiplatelet agent in HBR patients with chronic coronary syndrome treated by DCB angioplasty and standard duration of DAPT, followed by maintenance of single antiplatelet agent without clinical event for at least 1 year from the index procedure.

Detailed description

In patients with chronic coronary syndrome, the benefit of percutaneous coronary intervention (PCI) has been controversial for a survival benefit while reducing the risk of spontaneous myocardial infarction (MI) or anginal symptoms. Therefore, unlike patients with acute coronary syndrome, routine PCI with drug-eluting stents (DES) for patients with chronic coronary syndrome should be individualized, considering the risk of long term possibility of stent failure and the need for maintaining dual antiplatelet therapy (DAPT) for certain period due to permanent vascular implant and increased risk of bleeding, especially in patients with high bleeding risk (HBR). Drug-coated balloon (DCB), a novel treatment strategy, which has benefit of having shorter antiplatelet therapy duration due to the absence of metallic scaffolds and polymers, could be an alternative treatment for patients with chronic coronary syndrome, especially in patients with HBR. Given the expanding indications for DCB including de novo coronary artery lesions, shorter duration of DAPT, and potentially reduced risk of bleeding might be a reasonable treatment strategy in patients with HBR.

In current guidelines, standard duration of DAPT after PCI is recommended for 1 to 3 months in patients with HBR. Then, it is recommended as Class IA recommendation for maintaining single antiplatelet agent for lifelong as a secondary prevention, regardless of the devices used during PCI and the risk of patients' bleeding risk. However, it should be noted that the supporting evidence for lifelong maintenance of single antiplatelet agent were derived from previous randomized controlled trials conducted in patients with acute myocardial infarction or stroke. In addition, the supporting evidence for lifelong maintenance of single antiplatelet agent after PCI was derived from the recent randomized controlled trials using metallic stents including bare metal stent, 1st generation DES, or 2nd generation DES. The gap in the evidence is that no previous trial evaluated the need of lifelong maintenance of single antiplatelet agent in HBR patients with chronic coronary syndrome treated by DCB angioplasty after standard duration of DAPT. Furthermore, although recent trial have shown that long-term antiplatelet monotherapy with clopidogrel demonstrated better clinical outcomes than antiplatelet monotherapy with aspirin in patients with chronic coronary syndrome undergoing PCI with DES, there has been scarce data regarding long-term antiplatelet therapy for HBR patients with chronic coronary syndrome treated by DCB angioplasty after standard duration of DAPT.

On this background, the current trial aims to compare clinical outcomes between discontinuation of antiplatelet agent and continuation of antiplatelet agent in HBR patients with chronic coronary syndrome treated by DCB angioplasty and standard duration of DAPT, followed by maintenance of single antiplatelet agent without clinical event for at least 1 year from the index procedure. Having this evidence will be able to more establish the evidence for the post-adjunctive medical treatment in patients with HBR after DCB angioplasty.

Interventions

• Other Discontinuation of antiplatelet agent group
  In this group, antiplatelet monotherapy will be discontinued at the time of randomization. Randomization will be performed at 1 year from the index procedure using DCB angioplasty, standard duration of DAPT (1-3 months), and maintenance of antiplatelet monotherapy at least 1 year from the index procedure in patients with HBR and chronic coronary syndrome. In patients who are still under DAPT at 1 year from index DCB angioplasty, all antiplatelet agents will be discontinued after randomization.
• Other Continuation of antiplatelet agent group
  In this group, lifelong antiplatelet monotherapy will be continued after the time of randomization. Randomization will be performed at 1 year from the index procedure using DCB angioplasty, standard duration of DAPT (1-3 months), and maintenance of antiplatelet monotherapy at least 1 year from the index procedure in patients with HBR and chronic coronary syndrome. In patients who are still under DAPT at 1 year from index DCB angioplasty, DAPT will be changed to single antiplatelet therapy (aspir

Primary outcome measures

• Major bleeding (BARC 2, 3, or 5 bleeding) [Time frame: 1 year after last patient enrollment]

Secondary outcome measures (12)

• Patient-oriented composite outcome [Time frame: 1 year after last patient enrollment]
• Cardiovascular death [Time frame: 1 year after last patient enrollment]
• All-cause death [Time frame: 1 year after last patient enrollment]
• Target-vessel myocardial infarction [Time frame: 1 year after last patient enrollment]
• Non-fatal MI [Time frame: 1 year after last patient enrollment]
• Clinically indicated target-lesion revascularization (TLR) [Time frame: 1 year after last patient enrollment]
• Clinically indicated target-vessel revascularization (TVR) [Time frame: 1 year after last patient enrollment]
• Any revascularization [Time frame: 1 year after last patient enrollment]
• Cardiovascular death or target-vessel MI [Time frame: 1 year after last patient enrollment]
• All-cause death or non-fatal MI [Time frame: 1 year after last patient enrollment]
• Target vessel failure [Time frame: 1 year after last patient enrollment]
• Severe major bleeding (BARC 3 or 5 bleeding) [Time frame: 1 year after last patient enrollment]

Eligibility criteria

Inclusion criteria

• Subject must be at least 19 years of age
• Subject who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily.
• Patients with chronic coronary syndrome and at least one de novo lesion of reference vessel size ≥2.25 mm, treated with DCB angioplasty
• Patients with high bleeding risk: one or more of the criteria listed A. Age ≥ 75 years old B. Baseline Hemoglobin <11 g/dl (or anemia requiring transfusion during the 4 weeks prior to randomization) C. Any prior intra-cerebral bleed D. Hospital admission for bleeding during the prior 12 months E. Non skin cancer diagnosed or treated < 3 years F. Planned daily NSAID (other than aspirin) or steroids for >30 days after PCI G. Planned surgery that would require interruption of DAPT (within next 12 months) H. Renal failure defined as calculated creatinine clearance <40 ml/min or on dialysis I. Hematological disorders (platelet count <100,000/mm3 or any coagulation disorder) J. Severe chronic liver disease defined as patients who have developed any of the following: variceal hemorrhage, ascites, hepatic encephalopathy or jaundice K. Expected non-compliance to secondary prevention medications after PCI for other medical reasons
• Patients who completed standard duration of DAPT (1-3months) and followed by maintenance of single antiplatelet agent (aspirin or P2Y12 inhibitor) for at least 1 year from index procedure.
• No bleeding (BARC 2, 3, or 5 bleeding) or ischemic events (cardiovascular death, non-fatal MI, or clinically-indicated repeat revascularization) for at least 1 year from index procedure.

Exclusion criteria

• Patients unable to provide consent
• Patients with acute myocardial infarction or unstable angina
• Patients with known intolerance to aspirin, P2Y12 inhibitors, or components of DCB
• Patients with indication of oral anticoagulant
• Patients with concomitant drug-eluting stent implantation during index PCI
• Patients with history of ischemic stroke or previous myocardial infarction
• Patients with peripheral arterial occlusive disease
• Patients with angiographic findings of A. Left main coronary artery disease B. In-stent restenosis is the cause of target lesion C. Target lesion in bypass graft D. True bifurcation lesion that requires upfront 2-stenting E. Patients with residual stenosis on non-target vessels after PCI (>70% diameter stenosis or FFR≤0.80)
• Patients who have non-cardiac co-morbid conditions with life expectancy <1 year
• Patients who may result in protocol non-compliance (site investigator's medical judgment)
• Patients with cardiogenic shock or cardiac arrest
• Patients with severe left ventricular systolic dysfunction (ejection fraction <30%)
• Patients with severe valvular heart disease requiring open heart surgery
• Pregnant or lactating women

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

South Korea · 18 centers

• Korea University Ansan Hospital — Ansan
• Keimyung University Dongsan Medical Center — Daegu
• Gangneung Asan Hospital, University of Ulsan College of Medicine — Gangneung
• Ilsan Paik hospital — Goyang
• Chonnam National University Hospital, Chonnam National University Medical School — Gwangju
• Chung-Ang University Gwangmyeong Hospital — Gwangmyeong
• Catholic Kwandong University International St. Mary's Hospital — Incheon
• Gachon Cardiovascular Research Institute, Gachon University — Incheon
• … and 10 more centers

Identifiers

NCT: NCT06742931 · NCT314316452025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗