Section Structure
1. Highlights. 2. Clinical Background and Unmet Need. 3. LIFE-BTK Trial Design and Endpoints. 4. Three-Year Efficacy Results. 5. Safety and Limb Outcomes. 6. Predictors of Reintervention and Subgroup Findings. 7. Clinical Interpretation and Expert Commentary. 8. Limitations and Remaining Questions. 9. Conclusion. 10. Funding, Trial Registration, and Citation.
Highlights
The 3-year LIFE-BTK analysis suggests that the Esprit drug-eluting resorbable scaffold (DRS) provides a durable vessel-related benefit over percutaneous transluminal angioplasty (PTA) in infrapopliteal chronic limb-threatening ischemia (CLTI), with a significantly higher primary efficacy endpoint by Kaplan-Meier analysis: 59.5% versus 44.8% (P = 0.0025).
DRS was associated with lower binary restenosis at 3 years than PTA (38.0% vs 49.0%) and a numerically lower rate of clinically driven target lesion revascularization (CD-TLR) (10.2% vs 18.4%). In multivariable Cox regression, DRS treatment was linked to a lower hazard of CD-TLR, with a hazard ratio of 0.46 (95% CI: 0.22-0.97).
Despite the patency and reintervention advantage, major limb outcomes remained broadly similar between groups. Limb salvage was high in both arms (93.8% with DRS vs 95.7% with PTA), and the primary safety endpoint was also comparable (90.8% vs 94.2%).
The findings strengthen the case for a scaffold-based drug-delivery strategy in selected patients with below-the-knee disease, while also underscoring the need for cautious interpretation because only 57% of patients completed 3-year follow-up.
Clinical Background and Unmet Need
CLTI is the most severe clinical presentation of peripheral artery disease and is associated with ischemic rest pain, nonhealing ulcers, gangrene, repeated hospitalizations, amputation risk, cardiovascular events, and excess mortality. Infrapopliteal occlusive disease is especially challenging because these vessels are small caliber, frequently heavily calcified, and often affected by diffuse or multisegment disease. Patients commonly have diabetes, kidney dysfunction, neuropathy, infection, or prior tissue loss, all of which complicate procedural success and durable healing.
Endovascular therapy has become a major revascularization approach for below-the-knee disease, particularly in patients who are poor surgical candidates or who lack an optimal conduit for bypass. However, standard PTA has important limitations. Although it can restore flow acutely, elastic recoil, dissection, neointimal hyperplasia, and recurrent narrowing are common. These mechanisms contribute to high rates of restenosis and repeat intervention, especially in complex tibial lesions.
Drug-device technologies seek to address this gap. A resorbable scaffold offers temporary mechanical support, local drug delivery, and eventual bioresorption, theoretically reducing chronic foreign-body burden while maintaining vessel patency during the critical healing period. The LIFE-BTK program has been clinically important because it tested this concept in a randomized fashion in a population with CLTI, where durable technical success must ultimately translate into maintained perfusion, wound healing support, and limb preservation.
LIFE-BTK Trial Design and Endpoints
LIFE-BTK was a randomized trial that enrolled 261 patients with CLTI and infrapopliteal artery disease. Participants were assigned in a 2:1 ratio to treatment with the Esprit BTK drug-eluting resorbable scaffold or to conventional PTA. The present report extends prior 1-year and 2-year findings to 3 years.
The study’s primary efficacy endpoint was a composite centered on vessel durability and clinically relevant target-limb outcomes: freedom from above-ankle amputation in the target limb, target vessel occlusion, clinically driven target lesion revascularization, and binary restenosis of the target lesion. The primary safety endpoint was freedom from major adverse limb events and perioperative death.
This endpoint framework is notable because it goes beyond simple angiographic patency. In CLTI, an isolated lumen-based endpoint may miss the wider clinical context; however, a purely clinical endpoint can be insensitive to device-specific vascular benefit. The composite used here attempts to capture both. At the same time, interpretation still requires attention to which components are driving the overall result, because a reduction in restenosis or reintervention does not automatically imply a reduction in amputation or mortality.
Three-Year Efficacy Results
At 3 years, 57% of patients completed follow-up. Despite this attrition, Kaplan-Meier analysis showed a sustained benefit in the primary efficacy endpoint for DRS compared with PTA: 59.5% versus 44.8%, with a P value of 0.0025. This is the central finding of the report and suggests that the benefit seen at 1 and 2 years was not transient.
The most plausible drivers of this advantage were vessel patency-related outcomes. Binary restenosis was less frequent in the DRS arm than in the PTA arm, 38.0% versus 49.0%. Clinically driven target lesion revascularization was also lower with DRS, 10.2% versus 18.4%, although the abstract describes this difference as numerical rather than definitively statistically significant in the direct arm comparison.
Importantly, the multivariable Cox model provides additional support for the reintervention signal. After adjustment, treatment with DRS was associated with a significantly lower hazard of CD-TLR compared with PTA, with a hazard ratio of 0.46 and a 95% confidence interval of 0.22 to 0.97. In practical terms, this suggests that DRS nearly halved the adjusted risk of requiring clinically driven repeat treatment of the target lesion over 3 years.
From a clinician’s perspective, these are meaningful findings. Reinterventions in CLTI are not trivial. They are often performed in frail patients with diabetes, tissue loss, infection risk, chronic kidney disease, and limited mobility. Each repeat procedure carries procedural risk, cost, contrast burden, and the possibility of hospitalization. A durable reduction in restenosis and repeat intervention therefore has genuine clinical value, even if the effect on major amputation is less obvious.
Safety and Limb Outcomes
The major safety message is one of broad comparability between the two strategies. The primary safety endpoint occurred at similar rates, with freedom from major adverse limb events and perioperative death reported at 90.8% in the DRS arm and 94.2% in the PTA arm. Limb salvage was also high and similar: 93.8% with DRS versus 95.7% with PTA.
These data are reassuring in two ways. First, they do not indicate a late safety penalty from use of a resorbable scaffold in this vascular bed. That point matters because permanent metallic implants in small tibial arteries have historically raised concerns about fracture, chronic inflammation, and challenges with future access or surgery. Second, the similar limb salvage rates emphasize that the scaffold’s advantage appears primarily related to patency maintenance and reduced need for repeat procedures, rather than a clearly demonstrated superiority in preventing major amputation through 3 years.
That distinction is clinically important. In CLTI, amputation risk is determined not only by target lesion patency but also by wound burden, infection control, pedal runoff, microvascular disease, neuropathy, nutritional status, and multidisciplinary foot care. A device may improve vessel durability without necessarily overcoming all the downstream determinants of limb loss.
Predictors of Reintervention and Subgroup Findings
The multivariable analysis identified several independent predictors of CD-TLR in addition to treatment assignment. Previous minor amputation, greater preintervention stenosis, higher residual stenosis after predilatation, and use of postprocedure dual antiplatelet therapy were associated with reintervention risk.
Some of these predictors are intuitive. Previous minor amputation likely marks advanced limb disease, impaired tissue bed integrity, and a biologically high-risk limb. Greater baseline stenosis and higher residual stenosis after predilatation indicate more severe or technically resistant lesions. These findings reinforce the procedural principle that lesion preparation matters in below-the-knee intervention. A vessel that remains significantly narrowed after predilatation is less likely to have an optimal long-term result, regardless of the definitive device.
The association with postprocedure dual antiplatelet therapy is more difficult to interpret causally. It may represent confounding by indication, where operators prescribed more intensive antiplatelet therapy to patients perceived as higher risk because of lesion complexity or procedural issues. Without a randomized antiplatelet comparison, this variable should not be overinterpreted as evidence of harm from dual antiplatelet therapy itself.
Subgroup analyses generally favored DRS across most patient and lesion characteristics for patency and reintervention outcomes. Although subgroup analyses are hypothesis-generating rather than definitive, the consistency of directional benefit is encouraging. It suggests that the scaffold’s effect may not be confined to a narrow anatomical niche, though careful patient selection remains essential.
Clinical Interpretation and Expert Commentary
The LIFE-BTK 3-year results are best understood as evidence of sustained device efficacy rather than proof of across-the-board superiority in all clinically important outcomes. The strongest signal is durable lesion-level benefit: less restenosis and fewer repeat procedures. For interventional specialists treating tibial disease, this is a meaningful advance because PTA alone has long been limited by poor durability.
There is also biological plausibility behind the findings. A drug-eluting resorbable scaffold combines transient radial support with local antiproliferative therapy during the period when recoil, dissection healing, and neointimal proliferation are most likely to threaten patency. The later resorption of the scaffold may reduce some of the theoretical disadvantages of a permanent implant in a small, mobile artery. This hybrid concept is particularly attractive in infrapopliteal vessels, where long-term implant burden has always been a concern.
At the same time, clinicians should not equate improved patency with automatic improvement in all patient-centered endpoints. In CLTI, successful care requires a systems approach: revascularization, wound care, infection control, offloading, glycemic management, renal and cardiovascular risk management, and surveillance. The relatively similar limb salvage outcomes in this report remind us that revascularization is necessary but often not sufficient.
Current practice guidelines for CLTI emphasize individualized revascularization planning based on anatomy, limb severity, patient risk, and institutional expertise. The LIFE-BTK results fit well within that framework. They support DRS as a potentially valuable endovascular option in selected infrapopliteal lesions, especially when the goal is to improve durability over standard angioplasty alone. They do not, however, eliminate the need for surgical bypass in anatomically suitable patients, nor do they establish DRS as the universal default treatment for all below-the-knee disease.
Limitations and Remaining Questions
The most immediate limitation is incomplete long-term follow-up. Only 57% of patients completed the 3-year visit. Although time-to-event methods can help preserve interpretability, attrition raises concern for bias, especially in a CLTI population where death, frailty, and care fragmentation are common. The magnitude and direction of any bias cannot be fully determined from the abstract alone.
A second issue is the difference between lesion-oriented efficacy and hard limb outcomes. The trial demonstrates better patency-related performance, but the abstract does not show a parallel improvement in limb salvage. This does not negate the value of the device, but it means that clinicians should present the likely benefit accurately to patients: fewer restenoses and fewer repeat procedures are more clearly supported than a reduction in major amputation.
Third, external validity matters. Outcomes in randomized device trials can depend on lesion selection, operator experience, imaging protocols, and wound-care infrastructure. Whether similar benefits will be reproduced in broader real-world practice, including centers with different expertise and patient complexity, remains an important question.
Fourth, the study raises practical issues that are not fully answered in the abstract: optimal lesion preparation, best antiplatelet regimen, management of long or diffuse disease, cost-effectiveness, and how DRS compares not only with PTA but also with other contemporary technologies. As the field evolves, comparative effectiveness research will be needed to determine where scaffold-based therapy fits among drug-coated balloons, atherectomy-assisted approaches, specialty balloons, and bypass surgery.
Conclusion
The 3-year LIFE-BTK results provide persuasive evidence that the Esprit BTK drug-eluting resorbable scaffold delivers a sustained patency advantage over PTA in patients with infrapopliteal CLTI. The scaffold reduced restenosis and was associated with fewer reinterventions, while maintaining a safety profile and limb salvage rate comparable to angioplasty.
For clinicians, the practical message is clear but measured. In selected patients with below-the-knee CLTI, DRS appears to improve vascular durability beyond what balloon angioplasty alone can achieve. That may translate into fewer repeat procedures and a more stable revascularization course. However, the absence of an obvious limb-salvage advantage in the abstract and the incomplete 3-year follow-up mean that adoption should remain thoughtful, anatomy-specific, and integrated into comprehensive CLTI care.
Overall, LIFE-BTK moves the field forward. It supports the view that device innovation in tibial arteries can produce durable benefit, but it also highlights the continuing need for multidisciplinary care, rigorous surveillance, and further long-term comparative studies focused on patient-centered outcomes.
Funding, Trial Registration, and Citation
Trial: Pivotal Investigation of Safety and Efficacy of Drug-Eluting Resorbable Scaffold Treatment-Below the Knee (LIFE-BTK).
ClinicalTrials.gov identifier: NCT04227899.
Journal citation: Parikh SA, DeRubertis BG, Bonaca MP, Krishnan P, Pin RH, Lee JK, Metzger DC, Kolluri R, Shishehbor MH, Holden AH, Iida O, Armstrong E, Kum SWC, O’Connor DJ, Bajakian DR, Garcia LA, Ying SW, Wang J, Ruster K, Martinsen BJ, Igyarto Z, Varcoe RL. Long-Term Outcomes of a Drug-Eluting Resorbable Scaffold vs Angioplasty in Infrapopliteal Chronic Limb-Threatening Ischemia: 3-Year Results From the LIFE-BTK Trial. Journal of the American College of Cardiology. 2026-05-13. PMID: 42126372. URL: https://pubmed.ncbi.nlm.nih.gov/42126372/
The abstract provided does not specify detailed funding language beyond device and trial identification. Readers should consult the full article for complete disclosures, funding source details, and author conflict-of-interest statements.
