Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial

Marlon I Spreen, Jasper M Martens, Bettina E Hansen, Bob Knippenberg, Elke Verhey, Lukas C van Dijk, Jean-Paul P M de Vries, Jan-Albert Vos, Gert Jan de Borst, Evert-Jan P A Vonken, Jan J Wever, Randolph G Statius van Eps, Willem P Th M Mali, Hans van Overhagen, Marlon I Spreen, Jasper M Martens, Bettina E Hansen, Bob Knippenberg, Elke Verhey, Lukas C van Dijk, Jean-Paul P M de Vries, Jan-Albert Vos, Gert Jan de Borst, Evert-Jan P A Vonken, Jan J Wever, Randolph G Statius van Eps, Willem P Th M Mali, Hans van Overhagen

Abstract

Background: Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions.

Methods and results: Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia-related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03).

Conclusions: In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289.

Keywords: angioplasty; drug-eluting stents; ischemia; peripheral arterial disease.

© 2016 The Authors.

Figures

Figure 1.
Figure 1.
Flow chart, modified-intention-to-treat population. BMS indicates bare metal stent; CLI, critical limb ischemia; CTA, computed tomographic angiography; DES, drug-eluting stent; DSA, digital subtraction angiography; FU, follow-up; and PTA, percutaneous transluminal angioplasty. *Four patients included for 2 limbs with 1 limb in each arm. †One of these patients died before 1 year FU. ‡Two of these patients died before 1 year FU.
Figure 2.
Figure 2.
Kaplan–Meier curves representing the estimated 2-year cumulative incidence rates of major amputation per limb after percutaneous transluminal angioplasty (PTA)±bare metal stent (BMS) and drug-eluting stent (DES).
Figure 3.
Figure 3.
Kaplan–Meier curves representing the estimated 2-year cumulative incidence rates of survival per patient after percutaneous transluminal angioplasty (PTA)±bare metal stent (BMS) and drug-eluting stent (DES).
Figure 4.
Figure 4.
Kaplan–Meier curves representing the estimated 2-year cumulative incidence rates of major amputation or death per limb after percutaneous transluminal angioplasty (PTA)±bare metal stent (BMS) and drug-eluting stent (DES).
Figure 5.
Figure 5.
Mean Rutherford categories at baseline, 6 and 12 months. BMS indicates bare metal stent; CI, confidential interval; DES, drug-eluting stent; and PTA, percutaneous transluminal angioplasty.
Figure 6.
Figure 6.
Mean ankle-brachial index at baseline, 6 and 12 months. BMS indicates bare metal stent; CI, confidential interval; DES, drug-eluting stent; and PTA, percutaneous transluminal angioplasty.
Figure 7.
Figure 7.
Mean toe pressure at baseline, 6 and 12 months. BMS indicates bare metal stent; CI, confidential interval; DES, drug-eluting stent; and PTA, percutaneous transluminal angioplasty.

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