Comparison of Fractional FLOW Reserve Outcomes With Drug-Coated Balloon-Based Versus Drug-Eluting Stent-Only Percutaneous Coronary Intervention Strategies (FLOW-DCB)

In the DCB-based PCI group, lesion preparation may include conventional, non-compliant, cutting, or scoring balloons and, when needed, other calcium-modification techniques. An adequately prepared lesion has expansion with a balloon-to-vessel diameter ratio of at least 0.90, residual diameter stenosis of 30% or less, TIMI grade 3 flow, and no flow-limiting dissection or risk of vessel closure. When these conditions are met, the operator will use a paclitaxel-coated DCB (SeQuent Please NEO), sized approximately 1:1 to the reference vessel and covering the prepared segment. DCB delivery within 30 seconds and inflation for 30-60 seconds are recommended when clinically tolerated. DES implantation is permitted for inadequate flow, residual stenosis greater than 30%, substantial recoil, a major dissection, or another procedural reason requiring immediate stenting. Such stenting is part of the assigned DCB-based strategy, not a treatment crossover.

In the DCB-based PCI group, lesion preparation may include conventional, non-compliant, cutting, or scoring balloons and, when needed, other calcium-modification techniques. An adequately prepared lesion has expansion with a balloon-to-vessel diameter ratio of at least 0.90, residual diameter stenosis of 30% or less, TIMI grade 3 flow, and no flow-limiting dissection or risk of vessel closure. When these conditions are met, the operator will use a paclitaxel-coated DCB (SeQuent Please NEO), sized approximately 1:1 to the reference vessel and covering the prepared segment. DCB delivery within 30 seconds and inflation for 30-60 seconds are recommended when clinically tolerated. DES implantation is permitted for inadequate flow, residual stenosis greater than 30%, substantial recoil, a major dissection, or another procedural reason requiring immediate stenting. Such stenting is part of the assigned DCB-based strategy, not a treatment crossover.

• Paclitaxel-coated balloon-based intervention

In the DES-only PCI group, the target or culprit lesion will be treated with a contemporary newer-generation DES according to clinical practice.

In the DES-only PCI group, the target or culprit lesion will be treated with a contemporary newer-generation DES according to clinical practice.

Follow-up coronary angiography will be performed at 6 months (±30 days; up to 9 months if necessary), and distal FFR beyond the target or culprit lesion will be measured with a commercially available pressure wire as the primary outcome.

Difference between FFR measured proximal and distal to the target or culprit lesion.

Change in distal FFR from baseline to follow-up in patients with a preprocedural FFR measurement.

Between-group differences in the total number and length of implanted stents

Between-group differences in minimum lumen diameter and percentage diameter stenosis of the target or culprit lesion

Distal FFR and trans-lesion ΔFFR at 6-7 versus 8-9 months.

Number of participants who die from cardiovascular causes, including sudden cardiac death; death due to acute myocardial infarction, heart failure, or cardiogenic shock; other cardiovascular causes; and death of unknown cause without an undisputed noncardiovascular cause.

Number of participants who die from any cause during follow-up.

Number of participants with myocardial infarction attributed to the target vessel treated during the index procedure. Myocardial infarction is adjudicated using the protocol criteria adapted from the Fourth Universal Definition of Myocardial Infarction.

Number of participants with myocardial infarction that does not result in death. Spontaneous and procedure-related myocardial infarctions are included when they meet the protocol criteria adapted from the Fourth Universal Definition of Myocardial Infarction.

Number of participants undergoing repeat percutaneous coronary intervention of the target lesion or coronary bypass surgery for target-lesion disease when revascularization is clinically indicated. The protocol requires diameter stenosis of at least 50% by quantitative coronary angiography together with corresponding ischemia on functional testing, ischemic electrocardiographic changes at rest, typical ischemic symptoms, a positive invasive physiological test (FFR ≤0.80 or instantaneous wave-free ratio ≤0.89), or diameter stenosis of at least 70% even without another ischemic criterion.

Number of participants undergoing repeat percutaneous coronary intervention or coronary bypass surgery involving any segment of the target vessel when revascularization is clinically indicated. Clinical indication is determined using the protocol criteria for angiographic stenosis and symptoms, electrocardiographic changes, functional testing, or invasive physiological testing.

Number of participants undergoing any coronary revascularization after the index procedure, including percutaneous coronary intervention or coronary bypass surgery in a target or nontarget vessel, regardless of whether the procedure is classified as clinically indicated.

Number of participants with definite or probable thrombosis involving the treated target lesion or an implanted stent. Stent thrombosis is classified according to Academic Research Consortium criteria. For an unstented drug-coated balloon-treated lesion, definite lesion thrombosis is angiographically confirmed thrombus at the treated site with evidence of acute ischemia, or pathologically confirmed thrombus. Probable lesion thrombosis is myocardial infarction associated with documented acute ischemia in the treated lesion's territory, without angiographic confirmation of thrombus or another obvious cause.

Number of participants who experience cardiovascular death or myocardial infarction attributed to the target vessel, whichever occurs first. Components are defined according to the protocol criteria.

Number of participants who die from any cause or experience a nonfatal myocardial infarction, whichever occurs first. Myocardial infarction is defined according to the protocol criteria.

Number of participants who experience cardiovascular death, target-vessel myocardial infarction, or clinically indicated target-vessel revascularization, whichever occurs first.

Number of participants who experience cardiovascular death, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization, whichever occurs first.

Number of participants with Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. These categories include overt bleeding requiring clinical evaluation or treatment (type 2), major bleeding (type 3), and probable or definite fatal bleeding (type 5), as defined in the protocol.