In recent years, the medical community has witnessed significant advancements in the treatment of vascular diseases, particularly coronary artery disease (CAD) and peripheral artery disease (PAD). Among these innovations, drug-coated balloon (DCB) angioplasty has emerged as a promising alternative to traditional stent implantation. Unlike stents, which leave a permanent metallic scaffold inside the vessel, DCBs deliver therapeutic agents directly to the arterial wall without leaving behind any foreign material. This characteristic positions DCBs as a potentially transformative approach in vascular interventions, aiming to reduce long-term complications and improve patient outcomes.
DCBs operate by utilizing an angioplasty balloon coated with antiproliferative drugs, most commonly paclitaxel, which inhibits the proliferation of smooth muscle cells that contribute to restenosis—the re-narrowing of arteries after interventions. The balloon is inflated at the site of the lesion, releasing the drug directly into the vessel wall within seconds, providing a localized therapeutic effect. This method contrasts with drug-eluting stents (DES), which combine scaffolding and drug delivery but remain permanently implanted, influencing vascular biomechanics and potentially triggering chronic inflammatory responses.
Despite the theoretical advantages of DCBs, their clinical adoption has been tempered by several challenges. Early trials demonstrated favorable outcomes in some contexts, especially in peripheral arteries, but comparative efficacy against stents in complex coronary lesions has remained a subject of debate. While DCBs eliminate issues related to permanent implants such as late stent thrombosis or in-stent restenosis, concerns about the durability of vessel patency after DCB angioplasty persist. Moreover, the pharmacokinetics of drug transfer and retention in the arterial wall vary considerably, depending on lesion morphology, vessel size, and procedural techniques.
Over the last two decades, an extensive body of research has sought to define the optimal use cases for DCB angioplasty. Large-scale randomized controlled trials have evaluated the safety and efficacy of these devices in various vascular territories. For peripheral artery disease, DCBs have gained regulatory approval and have been increasingly recommended as first-line therapy, especially in femoropopliteal lesions. The ability to avoid permanent implants is particularly advantageous in these vessels, where mechanical stress and vessel movement increase the risk of stent fracture and occlusion.
In coronary artery disease, however, the application of DCBs is more nuanced. Current guidelines generally reserve DCB use for specific clinical scenarios, such as treating in-stent restenosis or small-vessel disease, where stent implantation is less feasible or associated with high risk. The evidence supporting DCB-only angioplasty in de novo coronary lesions remains limited but is growing with ongoing trials examining long-term outcomes, vessel healing, and functional vessel remodeling after treatment.
The technical design of DCBs plays a critical role in their performance. Advances in balloon technology, coating formulations, and drug carriers have enhanced the efficiency of drug delivery and reduced adverse events. Contemporary DCB platforms utilize innovative excipients that facilitate rapid and homogeneous drug transfer without causing particle embolization downstream, which had been a concern with earlier iterations. Procedural optimization, such as lesion preparation through predilatation and ensuring adequate balloon contact, is vital to achieving effective drug uptake and preventing elastic recoil or dissection.
Mechanistically, the antiproliferative drugs used in DCBs interrupt the pathological repair processes following angioplasty-induced vessel injury. Paclitaxel, favored for its lipophilic nature and sustained retention in tissue, interferes with microtubule dynamics, halting smooth muscle cell mitosis and migration. Alternative agents, including sirolimus and its analogs, are under investigation to offer potentially improved safety profiles. Pharmacological and biomechanical synergy aims to stabilize the arterial wall and prevent restenosis without triggering chronic inflammation.
One of the most compelling benefits of DCBs derives from their potential to elicit positive vessel remodeling. By avoiding the rigidity and chronic inflammation caused by stents, arteries treated with DCBs have demonstrated the capacity to restore natural vasomotion, maintain endothelial function, and preserve future therapeutic options. These features are particularly relevant in young patients or those requiring multivessel treatment, where the preservation of native vessel architecture can have long-term clinical benefits.
Despite these promising developments, the journey of DCB technology has also encountered setbacks. Initial enthusiasm following early peripheral artery trials was curbed by meta-analyses suggesting increased mortality potentially linked to paclitaxel-coated devices, leading to more rigorous scrutiny by regulatory agencies. Subsequent evaluations and revised clinical protocols have reaffirmed the safety profile of DCBs, emphasizing the need for careful patient selection and informed consent.
Current clinical guidelines reflect a cautious endorsement of DCB technology, with nuanced recommendations based on lesion characteristics and patient comorbidities. In peripheral interventions, DCBs have achieved class I or IIa recommendations for femoropopliteal and infra-popliteal arteries. In the coronary field, DCB usage remains a niche but evolving area, contingent on further evidence from ongoing randomized trials that aim to substantiate restenosis rates, event-free survival, and quality-of-life improvements in diverse patient populations.
Looking toward the future, research continues to push the boundaries of DCB capabilities. Novel drug formulations, dual-coated balloons combining antiproliferative and anti-inflammatory agents, and personalized treatment algorithms are under exploration. Integration with intravascular imaging technologies is improving lesion assessment and procedural precision, maximizing the benefits of drug delivery while minimizing vascular trauma.
Moreover, combination strategies employing DCBs alongside newer bioresorbable scaffolds or as adjuncts in hybrid revascularization procedures offer intriguing possibilities to leverage the distinct advantages of each modality. The convergence of pharmacology, engineering, and clinical expertise is accelerating the refinement of device design, aiming to transform vascular interventions into minimally invasive, durable, and patient-tailored therapies.
In conclusion, drug-coated balloon angioplasty represents a paradigm shift in the management of CAD and PAD, offering a scaffold-free therapeutic alternative that addresses some inherent limitations of stent-based treatments. Although challenges remain, particularly regarding long-term efficacy and patient selection, ongoing clinical trials and technological advancements hold promise for expanding the role of DCBs in routine practice. As evidence accumulates and experience grows, DCB angioplasty may become a cornerstone in the evolving landscape of cardiovascular intervention, delivering improved outcomes and enhanced vessel preservation.
Subject of Research: Drug-coated balloon angioplasty in coronary and peripheral artery disease
Article Title: Drug-coated balloon angioplasty for coronary and peripheral artery disease: latest evidence and clinical indications
Article References: Durand, R., O’Callaghan, D., Coughlan, J.J. et al. Drug-coated balloon angioplasty for coronary and peripheral artery disease: latest evidence and clinical indications. Nat Rev Cardiol (2026). https://doi.org/10.1038/s41569-026-01262-2
Image Credits: AI Generated
DOI: 10.1038/s41569-026-01262-2
Keywords: Drug-coated balloon, DCB, coronary artery disease, peripheral artery disease, paclitaxel, angioplasty, restenosis, drug delivery, vascular intervention
