“The incidence of any amputation—planned or unplanned—was reduced in the sirolimus group.”
News Coverage ↗From published coverage, not an answer posted here.
Sirolimus-Coated Balloon Angioplasty for Infrainguinal Artery Disease
What happened
Sirolimus-coated balloons reduce 1-year major adverse limb events vs uncoated balloons in infrainguinal artery disease.
- Risk difference -4.9 percentage points
- 95% CI -8.5 to -1.3
- P<0.001 for noninferiority; P=0.009 for superiority
- n=1,252
Does this change practice?
Where experts agree
Both the trial investigators and an independent discussant agree that SirPAD provides convincing evidence of an efficacy signal for sirolimus-coated balloons in PAD, a question that prior surrogate-endpoint studies could not definitively answer.
What this trial adds
Experts read SirPAD as settling the efficacy question for sirolimus-coated balloons in peripheral artery disease, with the large all-comers design and hard clinical endpoints drawing particular praise.
Published field read
Reaction to SirPAD is broadly positive, with commentators highlighting that this is one of the first trials in the field powered for clinical outcomes rather than surrogate endpoints. The all-comers enrollment, including a large share of patients with limb-threatening ischemia, is seen as strengthening the real-world relevance. The live question is whether these results will be enough to shift guidelines and change practice patterns away from paclitaxel-based devices or uncoated balloons.
Still open
Questions raised in published commentaryExperts have not yet addressed how these results compare head-to-head with paclitaxel drug-coated balloons beyond the SIRONA non-inferiority finding, or whether guideline committees will act on the data.
Douglas Drachman's comment about wound heterogeneity suggests open questions about which limb-threatening ischemia subgroups benefit most.
Context from published commentary. Source summaries are not a new guideline recommendation.
Who says what
Sahil Parikh
Practice takeInterventional cardiologist, Columbia University Irving Medical CenterThis trial puts to rest whether there is an efficacy signal with sirolimus
Original post ↗Douglas Drachman
Endpoint critiqueVascular medicine specialist, Massachusetts General HospitalWound heterogeneity matters when interpreting limb-threatening ischemia outcomes
Original post ↗Nils Kucher
Results readoutVascular medicine professor, University Hospital ZurichAll-comers design with nearly 50% limb-threatening ischemia powered hard clinical endpoints
Original post ↗Show 2 more perspectivesShow fewer perspectives
Nils Kucher and Stefano Barco
Guidelines questionAngiology, University Hospital ZurichCall for more randomized trials with clinical outcomes to guide treatment and shape future guidelines, while noting the unprecedented scale of enrollment in a PAD device study.
Original post ↗Manish Doshi
Concept Medical“At Concept Medical, we are committed to generating robust clinical evidence to support our innovative technologies. Following the successful completion of SIRONA—the largest superficial femoral artery (SFA) trial comparing our device against paclitaxel drug-coated balloons (DCBs), which demonstrated non-inferiority—we are proud to announce the completion of enrollment for another historical milestone: the largest randomised clinical trial for peripheral all-comers patients, completed enrolment of 1250+ patients. With this achievement, Concept Medical continues to lead the way with the most extensive and advanced clinical trial program in the field, reinforcing our position as a global pioneer in patient-centric vascular innovations.”
News Coverage ↗What should the author answer first?
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Full evidence
Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Full evidence
Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Why the trial?
The SirPAD trial was conducted to determine whether sirolimus-coated balloon angioplasty reduces the incidence of major adverse limb events compared to uncoated balloon angioplasty in patients with infrainguinal artery disease.
Does angioplasty with a sirolimus-coated balloon reduce major adverse limb events in patients with infrainguinal artery disease?
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Key Points
- To evaluate whether sirolimus-coated balloon angioplasty reduces the incidence of major adverse limb events compared to uncoated balloons in patients with infrainguinal artery disease.
- Prospective, open-label, noninferiority trial with blinded outcome adjudication that randomly assigned 1252 patients 1:1 to angioplasty with sirolimus-coated balloons (N=626) or uncoated balloons (N=626) (NCT04238546).
- Patients were evaluated at 1 year for the primary composite outcome of unplanned major target-limb amputation or target-lesion revascularization for critical limb ischemia, using a noninferiority margin of 5 percentage points with sequential testing for superiority.
- The primary outcome occurred in 8.8% (55/626) of patients in the sirolimus-coated group versus 15.0% (94/626) in the uncoated group (risk difference: -4.9 percentage points; 95% CI, -8.5 to -1.3; P<0.001 for noninferiority, P=0.009 for superiority).
- Key secondary limb events occurred in 23.0% (144/626) of the sirolimus group compared to 30.8% (193/626) of the uncoated group (risk difference: -7.8 percentage points; 95% CI, -12.7 to -2.9; P=0.002), with similar 1-year all-cause mortality rates of 11.8% versus 12.8% (risk difference: -1.0 percentage points; 95% CI, -4.6 to 2.7; P=0.67).
Study Design
Type
RCT (n=1,252)
Blinding
Open-label
Randomization
1:1 ratio
Structured PICO
Does angioplasty with a sirolimus-coated balloon reduce major adverse limb events in patients with infrainguinal artery disease?
P
Population
1,252 patients with infrainguinal artery disease (median age 75, 35.1% women) undergoing endovascular treatment, followed for 1 year.
I
Intervention
Angioplasty with a sirolimus-coated balloon
C
Comparator
Angioplasty with an uncoated balloon
O
Outcome
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 randomizationcomposite
Main Result
Mean Difference: -4.9 (95% CI -8.5–-1.3)
Absolute Event Rate: 8.8% vs 15%
Absolute Risk Reduction: 4.9%
p-value: p=<0.001 for noninferiority; P=0.009 for superiority
Sirolimus-coated balloon angioplasty significantly reduces the incidence of major adverse limb events at 1 year compared to uncoated balloons in patients with infrainguinal artery disease.
Discussion
No takes yet. Share an insight, caveat, or question.
Expert reaction
What experts said about SirPAD
NEJM · ACC Annual Scientific Session 2025
Expert labels are toward SirPAD's result, from named public quotes (n=0). As of Aug 30, 2026.
Where experts stand
Experts read SirPAD as settling the efficacy question for sirolimus-coated balloons in peripheral artery disease, with the large all-comers design and hard clinical endpoints drawing particular praise.
Reaction to SirPAD is broadly positive, with commentators highlighting that this is one of the first trials in the field powered for clinical outcomes rather than surrogate endpoints. The all-comers enrollment, including a large share of patients with limb-threatening ischemia, is seen as strengthening the real-world relevance. The live question is whether these results will be enough to shift guidelines and change practice patterns away from paclitaxel-based devices or uncoated balloons.
Agreement
Both the trial investigators and an independent discussant agree that SirPAD provides convincing evidence of an efficacy signal for sirolimus-coated balloons in PAD, a question that prior surrogate-endpoint studies could not definitively answer.
2 clinicians say this directly
Still unclear
Experts have not yet addressed how these results compare head-to-head with paclitaxel drug-coated balloons beyond the SIRONA non-inferiority finding, or whether guideline committees will act on the data. Douglas Drachman's comment about wound heterogeneity suggests open questions about which limb-threatening ischemia subgroups benefit most.
Key expert perspectives
“Sirolimus-coated balloons represent a promising technology in treating symptomatic PAD, supported by evidence primarily from studies with surrogate endpoints. While trials like SIRONA and ongoing studies such as SirPAD are expanding knowledge, robust data from randomized controlled trials with clinical outcomes are needed to guide treatment and shape future guidelines. This result, having been able to randomize so many patients in a PAD device study, is unprecedented and we are very thankful to all investigators and patients for having supported the trial.”
SPSahil ParikhInterventional cardiologist, Columbia University Irving Medical CenterPractice takeAug 30
This trial puts to rest whether there is an efficacy signal with sirolimus
Parikh views SirPAD as definitive evidence that sirolimus-coated balloons work in PAD, stating the trial resolves the outstanding efficacy question.
Distilled from their postOriginal post
DDDouglas DrachmanVascular medicine specialist, Massachusetts General HospitalEndpoint critiqueAug 30
Wound heterogeneity matters when interpreting limb-threatening ischemia outcomes
Drachman flags that not all ischemic wounds are equivalent, noting the difference between a deep penetrating heel ulcer and a superficial toe ulcer, which may affect how broadly the results apply.
Distilled from their postOriginal post
Implication
Strengthens case for sirolimus-coated balloons in infrainguinal interventions; confirms superiority over uncoated balloons in large RCT.
Abstract
BACKGROUND: Whether sirolimus-coated balloon angioplasty for infrainguinal artery disease reduces the incidence of major adverse limb events remains unknown. METHODS: In this prospective, open-label, noninferiority trial with a prespecified sequential testing strategy for superiority and blinded outcome adjudication, we 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 noninferiority margin was 5 percentage points. The primary safety outcome was death from any cause within 1 year after randomization. RESULTS: A total of 1252 patients were enrolled in the trial: 626 patients were assigned to the sirolimus-coated-balloon group and 626 to the uncoated-balloon group. The median age of the patients was 75 years, and 35.1% were women. A primary-outcome event occurred in 55 patients (8.8%) in the sirolimus-coated-balloon group and in 94 patients (15.0%) in the uncoated-balloon group (median unbiased estimate of risk difference, -4.9 percentage points; 95% confidence interval [CI], -8.5 to -1.3; P<0.001 for noninferiority; P = 0.009 for superiority); a key secondary-outcome event occurred in 144 patients (23.0%) and 193 patients (30.8%), respectively (risk difference, -7.8 percentage points; 95% CI, -12.7 to -2.9; P = 0.002). Death occurred in 74 patients (11.8%) in the sirolimus-coated-balloon group and in 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). The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with infrainguinal artery disease undergoing endovascular treatment, angioplasty with sirolimus-coated balloons led to a lower incidence of major adverse limb events at 1 year than angioplasty with uncoated balloons. (Funded by Concept Medical and others; SirPAD ClinicalTrials.gov number, NCT04238546.).
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Barco et al. (2026) conducted an RCT in Infrainguinal artery disease (n=1,252). Sirolimus-coated balloon angioplasty vs. Uncoated balloon angioplasty was evaluated on 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 (Risk difference -4.9 percentage points, 95% CI -8.5 to -1.3, p=<0.001 for noninferiority; P=0.009 for superiority). Sirolimus-coated balloon angioplasty was superior to uncoated balloons for reducing major adverse limb events (8.8% vs 15.0%; RD -4.9%; P<0.001 for noninferiority, P=0.009 for superiority).