For patients with symptomatic infrainguinal artery disease, angioplasty with a sirolimus-coated balloon, compared with an uncoated balloon, reduced major adverse limb events (MALE) at one year, according to the SirPAD trial results presented during a Late-Breaking Clinical Trial session at ACC.26 and simultaneously published in NEJM.

The investigator-initiated all-comers trial was conducted at 44 vascular care centers in Switzerland from November 2020 through December 2024. Eligible adult patients had symptomatic peripheral artery disease in the femoropopliteal arteries or arteries below the knee that warranted endovascular intervention and they were referred to one of two trial sites for enrollment and endovascular procedures that were performed by 15 operators.

Stefano Barco, MD, et al., enrolled 1,252 patients, with half randomized to a sirolimus-coated-balloon group and half to an uncoated-balloon group. The median age of patients was 75 years and 35% were women.

The open-label, noninferiority trial used a prespecified sequential testing strategy for superiority and blinded outcome adjudication. 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 (CLI) within one year. The key secondary outcome was a composite of any unplanned amputation affecting the target limb or revascularization of the target lesion for CLI or non-CLI within one year.

Results at one year showed that 55 patients (8.8%) in the sirolimus coated balloon group and 94 patients (15.0%) in the uncoated balloon group experienced a primary outcome event. The median unbiased estimate of risk difference was −4.9 percentage points (95% CI, −8.5 to −1.3; p<0.001 for noninferiority; p=0.009 for superiority). The difference in primary outcome events was driven by “concordant effects on both individual components of the primary composite outcome.”

For the key secondary outcome, an event occurred in 144 patients (23.0%) and 193 patients (30.8%) in the sirolimus coated balloon group and uncoated balloon group, respectively (absolute risk difference, −7.8 percentage points; 95% CI, −12.7 to −2.9; p=0.002 for superiority).

In the sirolimus coated balloon group, 74 patients died (11.8%) compared with 80 patients (12.8%) in the uncoated balloon group (risk difference, −1.0 percentage points; 95% CI, −4.6 to 2.7; p=0.67).

There was a similar rate of adverse events in the two groups (11.8% and 12.8% in the sirolimus-coated and uncoated balloon groups).

“The SirPAD trial showed that angioplasty with a sirolimus-coated balloon was both noninferior and superior to angioplasty with an uncoated balloon with respect to [MALE] in an unselected population of patients with symptomatic infrainguinal artery disease,” write the authors.

In a related editorial comment, Ehrin J. Armstrong, MD, FACC, writes that SirPAD is different from previous trials of new endovascular devices because it was a “strategy-based trial that enrolled a substantial percentage of patients with CLI who are typically excluded from device trials.”

“These data also suggest that sirolimus-based technologies provide substantial benefit in the endovascular treatment of peripheral artery disease,” writes Armstrong. “Together, the results from these trials may provide a wealth of data on the efficacy of sirolimus- and everolimus-eluting technologies and substantially advance the endovascular care of patients with complex peripheral artery disease.”

Clinical Topics: Vascular Medicine, Atherosclerotic Disease (CAD/PAD)

Keywords: ACC Annual Scientific Session, ACC26, New Orleans, Peripheral Arterial Disease