Three-Year Sustained Clinical Efficacy of Drug-Coated Balloon Angioplasty in a Real-World Femoropopliteal Cohort

Abstract

Purpose: To report the 36-month outcomes from the prospective, multicenter, single-arm IN.PACT Global Study (ClinicalTrials.gov identifier NCT01609296) evaluating the performance of the IN.PACT Admiral drug-coated balloon (DCB) in real-world patients with femoropopliteal occlusive disease. Materials and Methods: The IN.PACT Global Study was conducted at 64 international sites and enrolled 1535 patients with complex lesions, which included bilateral disease, multiple lesions, de novo in-stent restenosis, long lesions, and chronic total occlusions. The predefined full clinical cohort included 1406 patients (mean age 68.6 years; 67.8% men) with claudication or rest pain treated with the study DCB. Mean lesion length was 12.09±9.54 cm; 18.0% had in-stent restenosis, 35.5% were totally occluded, and 68.7% were calcified. Freedom from clinically-driven target lesion revascularization (CD-TLR) was evaluated through 36 months. The safety composite endpoint was freedom from device- and procedure-related death through 30 days and freedom from major target limb amputation and clinically-driven target vessel revascularization within 36 months. All safety and revascularization events were reviewed by an independent clinical events committee. Results: The Kaplan-Meier estimate of freedom from CD-TLR through 36 months was 76.9%. The composite safety endpoint was achieved in 75.6% of patients. The 36-month all-cause mortality rate was 11.6%, and the major target limb amputation rate was 1.0%. The Kaplan-Meier estimate of freedom from CD-TLR through 36 months was significantly lower in patients with chronic limb-threatening ischemia (CLTI) compared with claudicants (67.6% vs 78.0%; p=0.003). Lesions affecting both the superficial femoral artery (SFA) and popliteal artery had lower Kaplan-Meier freedom from CD-TLR through 36 months (69.2%) than either isolated SFA (79.7%) or popliteal artery lesions (76.5%; log- rank p<0.001). Predictors of CD-TLR through 36 months included increased lesion length, reference vessel diameter ≤4.5 mm, in-stent restenosis, bilateral disease, CLTI, and hyperlipidemia. Conclusion: DCB angioplasty with the IN.PACT Admiral DCB for femoropopliteal disease in a diverse and complex real-world population is associated with sustained clinical efficacy and low rates of reinterventions at 3 years after the initial procedure.

Keywords: angioplasty; drug-coated balloon; femoropopliteal segment; mortality; peripheral artery disease; popliteal artery; superficial femoral artery; target lesion revascularization.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Giovanni Torsello received speaking honoraria from W.L. Gore & Associates and Medtronic. Konstantinos Stavroulakis received honoraria from Medtronic, Boston Scientific Corp, Philips, and Biotronik. Marianne Brodmann received speaking honoraria from Bard Peripheral Vascular, Biotronik, Medtronic, Spectranetics, and VIVA Physicians and is a consultant for Bard Peripheral Vascular, Biotronik, Medtronic, and Spectranetics. Antonio Micari is a compensated consultant for Medtronic and Boston Scientific Corp. Gunnar Tepe received research grants from Medtronic and is a compensated advisory board member for Medtronic. Pierfrancesco Veroux received research and clinical trial funds and honoraria from Medtronic, Abbott Vascular, Terumo Medical Corp, Cook Medical, W.L. Gore & Associates, and Bolton Medical. Andrew Benko received speaking honoraria from Medtronic, Boston Scientific Corp, and Cordis and research funding from Medtronic, Boston Scientific Corp, and Soundbite Medical. Frank E.G. Vermassen received speaking honoraria from Abbott Vascular, Boston Scientific Corp, Medtronic, and Philips and is a consultant for Medtronic and Philips. Michael R. Jaff is a noncompensated advisor for Abbott Vascular; a part-time employee of Boston Scientific; an advisor for Biotronik, Medtronic, Philips, Sanofi, Vactronix, and Vascular Therapies; and an equity investor in Embolitech, Gemini, and PQ Bypass. Thomas Zeller received speaking honoraria from Abbott Vascular, Bard Peripheral Vascular, Biotronik, Boston Scientific Corp, Cook Medical, Cordis, GLG, W.L. Gore & Associates, Medtronic, Philips, Spectranetics, Straub Medical, TriReme, Veryan, and VIVA Physicians; he is a consultant for Abbott Vascular, Bard Peripheral Vascular, Boston Scientific Corp, Cook Medical, W.L. Gore & Associates, Medtronic, and Spectranetics; and his clinic has received study funds or funds for research or clinical trials from 480 Biomedical, Abbott Vascular, B. Braun, Bard Peripheral Vascular, Bayer Pharma, Biotronik, Caveo Med, Contego Medical, Cook Medical, CSI, W.L. Gore & Associates, Innora, Intact Vascular, Medtronic, Mercator, Philips, Pluristem, Shockwave, Spectranetics, Terumo, TriReme, and Veryan. Jia Guo and Reka Dobranszki are full-time employees of Medtronic.

Figures

Figure 1.

Patient flowchart in the IN.PACT Global Study though 36 months (±60 days). In the full clinical cohort, 1406 patients were treated with the IN.PACT Admiral DCB and will be followed for 5 years.

Figure 2.

Kaplan-Meier curve of freedom from clinically-driven target lesion revascularization (CD-TLR) in the clinical cohort through 36 months. Bars represent the 95% confidence intervals. All target lesion revascularization events were adjudicated by the independent Clinical Events Committee.

Figure 3.

Subgroup analyses of freedom from clinically-driven target lesion revascularization (CD-TLR) using the Kaplan-Meier method through 36 months: (A) chronic limb-threatening ischemia [Rutherford category (RC) 4/5] compared with claudicants (RC 2/3); (B) diabetics vs nondiabetics; (C) lesions affecting both the superficial femoral artery (SFA) and popliteal artery vs SFA-only vs popliteal artery–only lesions; and (D) not-occluded vs occluded lesions. Bars represent 95% confidence intervals. All target lesion revascularization events were adjudicated by the independent Clinical Events Committee.

Figure 4.

A post hoc Kaplan-Meier analysis of freedom from all-cause mortality through 36 months capturing patients who were adjudicated by the Clinical Events Committee per study protocol as well as the survival status of an additional 90 patients originally lost to follow-up (22 of these patients had died within 36 months). Bars represent 95% confidence intervals.

Figure 5.

(A) Distribution of Rutherford category (RC) at baseline and at the follow-up intervals. (B) Changes in RC at the follow-up intervals compared with baseline to illustrate percentage of patients showing improvement.