Coronary Angioplasty with Drug-Coated Balloons: Pharmacological Foundations, Clinical Efficacy, and Future Directions

Drug-coated balloons (DCBs) have transformed percutaneous coronary intervention (PCI) by delivering antiproliferative drugs directly to the arterial wall, offering a stent-less approach that mitigates risks associated with permanent metallic implants. Initially developed for in-stent restenosis (ISR), DCBs have demonstrated robust efficacy in reducing neointimal hyperplasia and target lesion revascularization (TLR) rates across diverse coronary lesions, including small vessel disease (SVD), de novo lesions, and complex anatomies such as bifurcation lesions. Paclitaxel-coated balloons have long been the cornerstone of DCB therapy due to their established clinical outcomes, but sirolimus-coated balloons are emerging as a promising alternative with potentially superior safety profiles and sustained drug release. The pharmacological mechanism of DCBs relies on rapid drug transfer during brief balloon inflation, achieving high local concentrations without residual foreign material. Landmark trials, such as BASKET-SMALL 2, RESTORE SVD, and AGENT IDE, have demonstrated comparable or non-inferior outcomes of DCBs versus drug-eluting stents (DES) in specific settings, with lower rates of stent thrombosis and shorter dual antiplatelet therapy (DAPT) requirements. Despite these advances, challenges per- sist, including optimizing drug formulations, ensuring uniform delivery, and addressing calcified lesions. Ongoing research into novel coatings, dual-drug systems, and artificial intelligence (AI)-guided interventions is poised to redefine PCI strategies. This comprehensive review explores the pharmacological underpinnings, clinical applications, and future directions of DCBs, highlighting their transformative role in coronary artery disease (CAD) management.