Objective: To evaluate the clinical outcomes after endovascular treatment of native femoropopliteal lesions with a drug-coated balloon (DCB) and drug-eluting stent (DES) as a primary option in patients with symptomatic peripheral artery disease.

Methods: A comprehensive literature search was performed through PubMed and Embase databases. Studies written in the English language and reporting a direct comparison of the outcomes between primary angioplasty with DCB and primary stenting with DES were included. The endpoints were considered the primary patency (PP), clinical-driven target lesion revascularization (cdTLR), major adverse limb events (free-MALE), and freedom from all-cause mortality.

Results: Eleven studies were considered eligible for the metanalysis (3 randomized clinical trials and 8 cohort studies). Overall, 3231 femoropopliteal lesions in 3137 patients were included, with DCB and DES performed in 1951 and 1280 lesions, respectively. No differences were found in demographics, clinical limb presentation, lesions length [173.9±80.2 mm DES vs 195.1±103.3 mm DCB; odds ratio (OR) -2.44; 95% confidence interval (CI) -11.26 to 6.38; p=0.59] and total occlusions (OR 1.41; 95% CI 0.87-2.27; p=0.16). In the DCB group, there was a significant rate of adjunctive procedures such as atherectomy and bailout stenting OR 0.13 (95% CI 0.09-0.18; p<0.001). No differences among PP, cdTLR, free-MALE and freedom from all-cause mortality at 1 year for DCB and DES: OR 1.11 (95% CI 0.74-1.66, p=0.61); OR 1.01 (95% CI 0.72-1.41, p=0.97); OR 1.08 (95% CI 0.69-1.69, p=0.74) and OR 1.85 (95% CI 0.82-4.17, p=0.14) respectively. No differences were found at 2 years: OR 0.89 (95% CI 0.64-1.23, p=0.47); OR 0.79 (95% CI 0.49-1.27, p=0.32); OR 0.74 (95% CI 0.49-1.10, p=0.14); OR 1.21 (95% CI 0.75-1.96, p=0.44) respectively.

Conclusions: Both approaches proved to be effective and safe for treating complex femoropopliteal lesions, with comparable clinical outcomes between the 2 groups. In the DCB arm, adjunctive procedures such as atherectomy and bailout stenting were required to optimize the results.Clinical ImpactThe introduction of drug-coated technologies, such as drug-coated balloons (DCBs) and drug-eluting stents (DESs), has significantly improved clinical outcomes for native femoropopliteal lesions. However, despite ongoing advancements in drug-coated device technology, the optimal treatment approach remains unclear due to limited comparative data in the literature. This meta-analysis aims to bridge this gap by reviewing current evidence, highlighting the latest developments, and providing valuable insights that may aid clinical decision-making in the management of native femoropopliteal lesions.