Association Between Preoperative Below-The-Knee Runoff and Clinical Outcomes in Patients with Femoropopliteal Occlusive Disease Treated With Drug-Coated Balloons

Abstract

Objective:

The objective of this study was to investigate the relationship between preoperative below-the-knee (BTK) runoff and major adverse limb event (MALE)-free survival, as well as clinically-driven target lesion revascularization (CD-TLR) and all-cause mortality, in patients with femoropopliteal occlusive disease (FPOD) treated with drug-coated balloons (DCB).

Methods:

A large-scale, multicenter, prospective study was initiated in January 2021. Endpoint outcomes were obtained prior to December 31, 2024. The exposure of interest was BTK runoff, with the primary endpoint being MALE-free survival, and secondary endpoints being CD-TLR and all-cause mortality. Multivariate Cox regression was employed to control for confounding variables, and stratified analyses were conducted.

Results:

A total of 1757 participants (36.1% male) with a mean (SD) age of 71.2 (9.5) years were enrolled in the study. The median follow-up duration was 1.5 years. In the fully adjusted model, 1 runoff, 2 runoff and 3 runoff were associated with significantly lower incidences of MALE or death compared with 0 runoff (1 runoff: hazard ratio [HR]=0.75, 95% confidence interval [CI]: 0.56, 1.00, p=0.054; 2 runoff: HR = 0.63, 95% CI: 0.46, 0.87, p=0.006; 3 runoff: HR=0.49, 95% CI: 0.34, 0.72, p<0.001). In addition, 3 runoff demonstrated a lower incidence of CD-TLR (HR=0.56, 95% CI: 0.35, 0.90, p=0.017) and all-cause mortality (HR=0.47, 95% CI: 0.25, 0.89, p=0.021) compared with 0 runoff. There was a significant trend toward reduction in the incidence of all 3 endpoints with increasing numbers of BTK runoff vessels (p for trend <0.05). The relationship between BTK runoff and the endpoints was consistent across all subgroups, with no significant interaction observed.

Conclusions:

In patients with FPOD treated with DCB, a higher number of BTK runoff vessels was significantly associated with fewer MALE or death, fewer CD-TLR, and fewer deaths. This association was independent of traditional cardiovascular risk factors and represents an important stratification factor for patient outcomes (The PROMISING Study, NCT04826705).

Clinical Impact

This large, prospective multicenter study demonstrates that preoperative below-the-knee (BTK) runoff remains a strong and independent prognostic factor in patients undergoing femoropopliteal drug-coated balloon (DCB) therapy. Despite the antiproliferative benefits of DCBs, distal hemodynamics continue to influence procedural durability and long-term limb outcomes. Our findings show a graded reduction in MALE, CD-TLR, and mortality with increasing runoff vessels, independent of lesion complexity, stent implantation, and concomitant outflow intervention. These results reinforce the importance of systematic preprocedural runoff assessment and support incorporating BTK runoff into risk stratification, patient counseling, and surveillance planning in contemporary endovascular practice.