Jens et al. (2014) performed a systematic review to determine overall 1 to 48-month follow-up outcomes of RCTs (published up until November 2013) comparing different endovascular treatment strategies in below-the-knee arterial lesions in patients with CLI. Twelve studies with a total of 1145 patients were included, in which 90% of the patients suffered from CLI. On the basis of moderate evidence, the authors recommended PTA with optional bailout stenting as the preferred strategy. According to the authors, alternative strategies, including drug-eluting stents (DES) and balloons (DEB), must be first tested in larger and high quality randomised controlled trials before being considered as viable and safe treatment options. Along these lines, Canaud et al. (2014) identified 26 studies (11 of which were randomised controlled trials) concerning infrainguinal angioplasty with a total of 2407 limbs, with the goal of comparing the treatment outcomes of varying endovascular devices. Meta-analysis of studies comparing DEB with standard balloon angioplasty demonstrated a result in favour of DEB for preventing binary primary restenosis (odds ratio 0.27). The meta-analysis comparing DES with bare-metal stents favoured DES with regard to target lesion revascularization (OR 0.15), as well as binary primary restenosis (OR 0.23). Overall, however, drug-eluting technology did not prevent more deaths or amputations. Therefore, whether or not the short-term success of such treatment methods will be reflected in long-term clinical outcome (mortality/rate of amputation) remains to be seen.

In the randomised IN.PACT DEEP trial, Zeller et al. (2014) assessed the efficacy and safety of a special drug-eluting balloon (IA-DEB) compared to PTA for infrapopliteal arterial revascularization in patients with CLI. Twelve months following intervention, no significant difference regarding the primary efficacy and safety endpoints was seen. However, a trend towards an increased major amputation rate was observed in the IA-DEB group versus the PTA-arm (8.8% vs. 3.6%). As a result, this particular study was not able to demonstrate an advantage of IA-DEB treatment strategies over PTA for infrapopliteal lesions. In a second RCT including 72 patients this group compared the safety and efficacy of a novel paclitaxel-coated drug-eluting balloon (DEB) versus an uncoated balloon in PTA of de novo or native restenotic lesions of the infrapopliteal arteries in patients with claudication and critical limb ischemia (Zeller et al. 2015). In this trial, the primary performance endpoint (patency loss at 6 months) was 17.1% in the DEB group versus 26.1% in the PTA group (p = 0.298), and major amputations of the target extremity occurred in 3.3% versus 5.6% of the patients at 12 months, respectively. The authors concluded that the novel Passeo-18 Lux DEB has been proven to be safe and effective in infrapopliteal lesions with comparable outcomes to PTA.

Todd et al. (2013) analysed 418 endovascular tibial interventions in patients with CLI (333 PTA alone, 6 PTA + stent, 11 artherectomy only, 68 artherectomy + PTA). The results of artherectomy, PTA and artherectomy-assisted procedures (i.e., artherectomy + PTA) were compared. TASC D lesions were more frequent in the PTA alone group than in the artherectomy cohort (25% vs. 13%). No significant differences existed with respect to the early (30-day) outcomes of loss of patency (11% vs 13%), complications (8% vs 13%), or major amputation (17% vs 13%) in the PTA-alone group vs the atherectomy-assisted group. This was also true for the 3-year follow-up (PTA vs. artherectomy + PTA: primary patency rate 55% vs. 46%; secondary patency rate 89% vs. 89%; limb salvage 70% vs. 77%; patient survival 56% vs. 50%). Considering the additional cost and increased procedural time, these findings put into question the routine use of adjunctive atherectomy.

Shammas et al. (2012) performed a similar analysis of a randomised controlled trial, however with a population size of only 50 patients. They investigated whether or not patients with CLI and calcified stenoses in the infrapopliteal area benefit from artherectomy with a rotation catheter before angioplasty. Indeed, their data appear to support this hypothesis; 1 year following intervention, 93.3% of the artherectomy + PTA group were free from revascularisation of the target vessel, compared with 80% in the PTA-alone group. However, the reason the first group demonstrated a mortality rate of 0% after 1 year and the PTA group a mortality rate of 32% remains to be determined, as the additional artherectomy alone is not enough to account for such a difference, particularly when the rate of amputation between the two groups did not differ.

Lo et al. (2013) performed a retrospective chart review using prospectively collected data on all consecutive patients undergoing an attempt at infrapopliteal angioplasty for critical limb ischemia from 2004 to 2012. Infrapopliteal PTA (stenting 14%, multilevel intervention 50%) was performed in 459 limbs of 413 patients (59% male). The majority (79%) of interventions were performed for tissue loss with fewer performed for rest pain (12%), ALI (3%), or to treat a stenosis in the native outflow vessel of a previous bypass graft performed for CLI (6%). Technical success was achieved in 427 of 459 (93%) limbs. Postoperative complications developed in 52 patients (11%), 30-day mortality rate was 6%. Technical failures were only observed in TASC D- lesions. Survival at 1, 3, and 5 years was 83%, 64%, and 49%, respectively. One- and 5-year primary patency was 57% and 38% and limb salvage was 84% and 81%, respectively. Freedom from restenosis was 56% and 34% at 1 and 5 years, respectively, and freedom from any subsequent revascularization was 74% and 50% at 1 and 5 years, respectively. The authors concluded that infrapopliteal angioplasty can achieve limb salvage and survival rates at 5 years comparable to those of surgical bypass and thus can be considered a reasonable first-line therapy in the treatment of TASC A, B, and perhaps C lesions even in a patient with adequate conduit available. TASC D lesions should preferably be treated with bypass in patients who are suitable candidates for surgery.

The OLIVE registry is a prospective multicenter registry study that consecutively enrolled patients who received infrainguinal endovascular treatment for CLI (Iida et al. 2015). A total of 314 patients were enrolled, with 312 evaluable patients remaining. Mean age of the patients was 73 ± 10 years, and 65% of the patients were male. Diabetes mellitus and hemodialysis were observed in 71% and 52% of patients, respectively. With respect to limb condition, tissue loss and wound infection were 88% (Rutherford 5: 73%, Rutherford 6: 15%) and 15%, respectively. At 3 years, overall survival rate was 63.0%, freedom from major amputation was 87.9%, and freedom from reintervention was 43.2%. Three-year freedom from MALE was 84.0% and rate of wound recurrence at 3 years was 43.9%. After multivariable analysis, age, body mass index ≤18.5, dialysis, and Rutherford 6 were identified as predictors of 3-year major amputation or death. With respect to the results it is noteworthy that in this registry 50% of patients were on hemodialysis. Nevertheless, the OLIVE registry demonstrated that the 3-year clinical results of endovascular treatment were reasonable, despite high reintervention and moderate ulcer recurrence rates.

Vierthaler et al. (2015) reviewed 1244 patients undergoing 1414 peripheral endovascular interventions for CLI (rest pain, 29%; tissue loss, 71%) within the Vascular Study Group of New England (VSGNE) from January 2010 to December 2011. The overall survival rate (OS), amputation-free survival rate (AFS), and freedom from major amputation rate (FFA) were lower for patients treated for tissue loss than for patients treated for rest pain, with 1-year estimates of 80% vs.87%, 71% vs. 87%, and 81% vs. 94%, respectively. In this study, the independent factors associated with OS, AFS, and FFA after peripheral endovascular intervention differed. In a multivariable model the authors identified eight factors associated with reduced survival at 1 year and six variables predictive of major amputation at 1 year (Tables 9.1 and 9.2). The only common risk factor for OS, AFS, and FFA was dialysis, emphasizing the importance of renal function in patient prognosis. In contrast, congestive heart failure was associated with decreased OS and AFS. The differences in risk factors for survival vs amputation highlighted the difficulty in predicting composite end points such as AFS. Causes of death may range from cardiovascular causes, such as myocardial infarction, to stroke and to cancer. Conversely, prior major amputation was associated with a later major amputation but not with survival.

A further database of 728 patients undergoing endovascular treatment of the lower extremity for CLI was queried by Davies et al. (2015). Patients had an average age of 68 years. Tissue loss was the indication in 66% of the interventions, the other patients were treated for rest pain. The SFA was the site for 49% of the interventions, 17% were in one or more tibial arteries, and 34% were performed at the level of the SFA and tibial arteries. The overall technical failure rate was 4%. In this study, the outcomes of lower extremity endovascular intervention for CLI using the OPG proposed by the SVS (s.o.) were reported. The 30-day MACE rate was 3%, which was less than the stated OPG of 8%, but the 30-day MALE rate was 12%, which was much higher than the stated OPG of 8%. In the clinical high-risk group (age >80 years and tissue loss), the 30-day MACE rate was 3%, which was superior to the OPG of 18%, but the 30-day MALE rate was 19%, which was inferior to the OPG of 10%. In the anatomic high-risk group (infrapopliteal distal target), the 30-day MACE rate was 1%, which was superior to the OPG of 10% for this subgroup, but the 30-day MALE rate was 13%, which was inferior to the OPG of 9% for this subgroup. Overall mortality during follow-up was high, with patient survival rates of 49% ± 2% at 5 years. Median follow-up was 2.5 years. Major amputation occurred in 23% of the patients, with above-knee amputation occurring in 16% and below-knee amputation occurring in 7%. Overall freedom from MALE was 51% ± 2% at 5 years. In this study, endoluminal therapy for CLI was associated with an early low MACE rate but a high MALE rate. Longer-term outcomes after endovascular intervention for CLI remained relatively poor, with <40% success in objective performance outcomes at 5 years.

A total of 2110 infrainguinal bypasses performed on patients with CLI between 2003 and 2009 were identified in the VSGNE database (Simons et al. 2012). The mean patient age was 69.9 years, 5 years older than that of the simultaneously analysed cohort of patients with intermittent claudication (IC). 24.7% of CLI patients received a prosthetic conduit. Hospital mortality was low, at 2.1%, however reoperation was necessary in 15% of the cases, and the rate of wound infection was at 5.6%. One year after surgery, 13.6% of the patients had died and the rate of major amputations was at 12.2%. The primary graft patency was calculated to be 66.4%, while the secondary patency was 77.4%. The results for patients with CLI were therefore considerably worse than those with IC (Table 9.3).