Critical Limb Ischemia: Prognostic Factors and Endovascular Strategies

Abstract

Critical limb ischemia (CLI) is the final stage of peripheral arterial disease (PAD). Endovascular infrapopliteal treatment of patients with CLI using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. The PADI (Percutaneous transluminal Angioplasty and Drug-eluting Stents (DES) for Infrapopliteal lesions in critical limb ischemia) trial was conducted to assess whether DES improve patency and clinical outcome of infrapopliteal lesions. Adults with CLI and infrapopliteal lesions were randomized to receive PTA±BMS or DES. Primary endpoint was 6-month primary binary patency of treated lesions. Severity of treatment failure was assessed with an ordinal score, ranging from vessel restenosis (>50%), through occlusion, to clinical failure (re-intervention, major amputation, CLI-related death). 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). The ordinal score showed more severe treatment failures for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment (P=0.066). Less minor amputations (below ankle level) occurred after DES until 6 months post-treatment (P=0.03).Also at long-term up to 5 years follow-up, treatment of infrapopliteal lesions in CLI patients with DES yielded more favourable clinical results than with PTA±BMS. The estimated 5-year major amputation rate was lower in the DES arm than in the PTA±BMS arm (19.3% vs. 34.0%, respectively, P=0.091). The 5-year amputation-free survival and event-free survival (survival free from re-intervention or major amputation) rates were significantly higher in the DES arm (DES: 31.8% versus PTA±BMS: 20.4%; P=0.043; and DES: 26.2% versus PTA±BMS: 15.3%; P=0.041, respectively).Diabetes mellitus (DM) was highly prevalent in the PADI trial and as well in the JUVENTAS (reJUVenating ENdothelial progenitor cells via Transcutaneous intra-Arterial Supplementation) trial, a randomized controlled trial conducted in equivalent CLI patients. The two trials were pooled on patient level. The 5-year major amputation rate was higher in patients with DM than in non-diabetics (34.1% versus 20.4%, P=0.015). Death rates were comparable. Model factors with significant hazard ratios (HRs) in the multivariate analysis were baseline Rutherford category (HR 1.95; 95% CI 1.24-3.06) and ankle-brachial index (ABI) >1.4 (HR 2.78; 95% CI 1.37-5.64). CLI patients with DM are thus at significantly higher risk of major amputation than CLI patients without DM. This increased risk is associated with a higher prevalence of baseline ABI>1.4 and more severe ischemia at initial presentation in patients with DM.The prognostic value of the ABI concerning major amputation and survival in CLI patients with proven arterial obstructive disease was assessed in more detail in the same cohort of patients. Patients with a high (>1.4)/immeasurable ABI showed a significantly higher 5-year major amputation and lower 5-year amputation-free survival rates than those with an intermediate (0.7-1.4) and low (<0.7) ABI. High/immeasurable ABI at baseline was associated with a significantly higher risk of major amputation or death (HR 2.95, P<0.001). Incorporating high/immeasurable ABI in the existing PREVENT III prediction model regarding outcome in CLI significantly improved its performance.