Key Points
• In the randomized SirPAD trial, sirolimus-coated balloon angioplasty was noninferior and superior to uncoated balloon angioplasty for the primary endpoint of major adverse limb events in patients with symptomatic infrainguinal peripheral artery disease.
• The primary endpoint occurred in 8.8% of the sirolimus-coated balloon group versus 15.0% of the uncoated balloon group, for an absolute risk difference of minus 4.9% with P < 0.001 for noninferiority and P = 0.009 for superiority.
• At 1-year, all-cause mortality was similar between groups, with 11.8% in the sirolimus-coated balloon arm and 12.8% in the uncoated balloon arm, with no apparent safety signal.
Whether sirolimus-coated balloon angioplasty for infrainguinal artery disease reduces the incidence of major adverse limb events remains unknown. The SirPAD trial, prospective, open label, noninferiority trial with a prespecified sequential testing strategy for superiority and blinded outcome adjudication, the investigators randomly assigned patients with infrainguinal artery disease in a 1:1 ratio to undergo angioplasty with a sirolimus-coated balloon or with an uncoated balloon. The primary outcome was a composite of unplanned major amputation affecting the target limb or endovascular or surgical revascularization of the target lesion for critical limb ischemia within 1 year after randomization. The key secondary outcome was a composite of any unplanned amputation affecting the target limb or revascularization of the target lesion for critical or noncritical limb ischemia within 1 year after randomization. The non-inferiority margin was 5 percentage points. The primary safety outcome was death from any cause within 1 year after randomization. The results were presented at ACC 2026 with simultaneous publication in New England Journal of Medicine
Medical therapies such as dual pathway inhibition and lipid lowering therapy have reduced major adverse limb events in patients with peripheral artery disease, but high-quality evidence for endovascular devices remains limited, particularly for below the knee disease and for trials focused on clinically meaningful outcomes rather than imaging surrogates. Against that background, SirPAD was designed to compare a MagicTouch PTA sirolimus-coated balloon with any approved uncoated balloon in broad all-comers’ population.
SirPAD was an academic, open label randomized trial with blinded outcome adjudication conducted in Switzerland between 2020 and 2024 [NCT04238546]. Screening and follow up involved 44 vascular care centers, with randomization at 2 trial sites. A total of 1,252 patients were randomized in a 1 to 1 fashion, with 626 assigned to sirolimus-coated balloon angioplasty and 626 assigned to uncoated balloon angioplasty. The target lesion was defined as the main lesion responsible for symptoms, with at least 50% stenosis in a single angiographic plane.
The population reflected advanced PAD. Median age was approximately 75 years, about 35% were women, and roughly 40% had chronic Rutherford stage 4 to 6 disease, while about 7% had acute Rutherford stage IIa to III ischemia. Around 70% of target lesions were in the femoropopliteal segment, median lesion length was about 150 mm, and more than half of lesions were total occlusions. Bailout stenting was required in 35.5% of the sirolimus-coated balloon arm and 39.9% of the uncoated balloon arm.
This endpoint occurred in 55 patients, or 8.8%, in the sirolimus-coated balloon group compared with 94 patients, or 15.0%, in the uncoated balloon group. The absolute risk difference was minus 4.9%, with a 95% confidence interval of minus 8.5 to minus 1.3, meeting criteria for both noninferiority and superiority. The key secondary endpoint, a composite of any unplanned target limb amputation or target lesion revascularization for critical or noncritical limb ischemia, also favored sirolimus-coated balloon angioplasty. This endpoint occurred in 23.0% of the sirolimus-coated balloon group and 30.8% of the uncoated balloon group, for an absolute risk difference of minus 7.8% and P = 0.002 for superiority.
Looking at individual components, target lesion revascularization for critical limb ischemia occurred in 8.3% versus 13.3%, while unplanned major target limb amputation occurred in 1.3% versus 2.7%, both favoring the sirolimus-coated balloon strategy numerically. For the broader key secondary endpoint, any unplanned target limb amputation occurred in 5.9% versus 8.8%, and target lesion revascularization for critical or noncritical limb ischemia occurred in 19.8% versus 25.9%. Sensitivity analyses, including time to event analysis, competing risk modeling, and worst-case assumptions, were reported to be consistent with the primary findings. With respect to safety, the primary safety endpoint of all-cause death was similar between groups at 1 year, occurring in 74 patients, or 11.8%, in the sirolimus-coated balloon arm and 80 patients, or 12.8%, in the uncoated balloon arm. Serious adverse events occurred in 58.1% of both groups, and no serious adverse device effects were reported.
Overall, SirPAD provides randomized evidence that in symptomatic infrainguinal PAD, sirolimus-coated balloon angioplasty reduced major adverse limb events and repeat limb interventions compared with uncoated balloon angioplasty, without an apparent 1-year safety penalty. These findings add important clinical outcomes data to the growing evidence base for sirolimus-coated technology in peripheral intervention.