Optimizing Drug-Coated Balloon Outcomes: The Evolving Role of Vessel Preparation in Coronary and Peripheral Artery Interventions

Drug-coated balloon (DCB) therapy differs fundamentally from stent-based revascularization since the vessel itself becomes the treatment substrate. Consequently, vascular preparation is an important component of DCB therapy. This review therefore examines contemporary vessel preparation before DCB therapy across coronary and peripheral interventions, integrating lesion morphology, procedural outcomes, intravascular imaging, and clinical follow-up. Across vascular beds, the objective is not maximal plaque disruption, but sufficient modification of the dominant mechanical limitation to achieve predictable expansion, controlled vessel injury, and effective balloon–vessel wall contact. Subsequent failure after coronary DCB therapy has been associated with residual plaque burden and calcium morphology. Specialty balloons, atherectomy and intravascular lithotripsy have been associated with improved procedural success, lumen expansion, and calcium modification, with lower rates of flow-limiting dissection or bailout stenting in selected settings. Randomized evidence has generally demonstrated more consistent procedural than long-term clinical benefits. Moreover, much of the evidence supporting advanced calcium-modification strategies derives from stent-based interventions and cannot be directly extrapolated to DCB-only therapy. These findings favor a lesion-specific, preparation-dependent approach rather than routine escalation to increasingly aggressive technologies. Conventional balloons may be sufficient for mechanically responsive lesions, whereas scoring or cutting balloons, atherectomy, or intravascular lithotripsy should be selected according to lesion morphology and the specific mechanical limitation that persists after initial preparation. Intravascular imaging may facilitate objective assessment of a “DCB-ready” vessel, although validated preparation thresholds remain undefined. The question is thus not which preparation device is preferable but whether the vessel has been adequately prepared to receive the drug. Future studies should go beyond device-to-device comparisons and assess whether predefined, imaging-based preparation targets improve drug delivery, vessel healing, and durable clinical outcomes. The next step toward precision DCB therapy across coronary and peripheral disease may be to shift the focus from device selection to treatment-substrate optimization.