Because of the high restenosis rates following PTA alone, alternative endovascular modalities have been developed to improve patency rates. One approach designed to limit the inflammatory response following angioplasty is endovascular cryoplasty in which cold thermal energy is delivered simultaneously inside an angioplasty balloon. Experimentally, cryotherapy induces SMC apoptosis, which would theoretically halt the inflammatory response to vessel injury during balloon angioplasty. However, a single-center experience with 86 patients failed to demonstrate improved outcomes over expected patency rates from PTA (48–37 % at 12–24 months, respectively) [19]. Schmidt published a series in which 109 infrapopliteal lesions (the most challenging of the lower extremity lesions) were treated and reported improvement in 94 %, healing in 74 %, and a limb salvage rate of 95 % [20]. The single RCT of comparing cryotherapy to balloon angioplasty (COLD trial) demonstrated a mean patency of 79 % in the cryoplasty arm versus 67 % in the PTA arm (P  =  14) at 9 months and a 30 % rate of stent placement for residual stenosis or dissection following cryoplasty versus 39 % in the PTA group [21]. Long-term results are pending, but at this time cryoplasty does not appear to offer significant advantages over PTA.

Cutting balloons are designed with atherotome blades that score atherosclerotic plaques. This technique treats lesions while limiting overdilation of the vessel and therefore elastic recoil as well as distal dissection. Reports on their use in the coronary, pulmonary and peripheral vasculature indicated that there is in fact a reduction in vessel trauma and elastic recoil during CBA, with a positive impact in remodeling [22–28]. Initial results of this technology in femoropopliteal lesions demonstrated high rates of technical success (93 %), limb salvage (100 %), and primary patency (88 %) [29]. However, in a RCT of CBA versus PTA in short (<10 cm) SFA stenosis, CBA yielded increased restenosis rates at 6 months (62 %) compared to PTA (38 %) [30].

The theories on the precise role of endovascular interventions in femoropopliteal chronic total occlusions are in flux. Open surgical bypass remains the de facto gold standard, but dedicated re-entry catheters designed for subintimal angioplasty have been shown to be safe and the procedure technically feasible [31]. In light of the improvements in endovascular tools for subintimal navigation and vessel ­re-entry, as well as high rates of morbidity and mortality following open surgery in a subset of high-risk patients, increasing numbers of threatened limbs are being treated percutaneously [32]. Scott and colleagues published their single-center experience with 506 infrainguinal occlusions. Primary patency at 12–36 months was 45 % (SE 3.0 %) and 25 % (SE 3.6 %), respectively, and secondary patency was 76 % (SE 2.6 %) and 50 % (SE 4.8 %) at 12–36 months. Patients with femorotibial occlusions and critical limb ischemia had worse outcomes. Limb salvage in patients with CLI was 75 %, and open surgical bypass was avoided in 77 % at 36 months [33]. These results indicate that in experienced hands, subintimal angioplasty is a reasonable first-line therapy for patients with infrainguinal occlusions. The aforementioned results are unlikely to be a true representation of the outcomes to be expected in the average interventional community practice, as the procedure is anecdotally plagued by being extremely operator dependent.

Disappointing long-term patency rates following PTA in the femoropopliteal segment prompted the use of stents following angioplasty. Balloon angioplasty leads to thrombus formation, recoil, intimal hyperplasia, and ultimately negative remodeling, while stents are impacted only by thrombus formation and inflammatory-mediated intimal hyperplasia [34, 35]. Additionally, stents in the muscular infrainguinal arteries are subject to stresses that result in stent fracture, which also induces intimal hyperplasia and in-stent stenosis.

In the early years of infrainguinal endovascular interventions, stainless-steel stents were deployed with disappointing results. Studies failed to demonstrate improved outcomes over angioplasty alone, and the indication for stents was limited to bail-out for residual stenosis or arterial dissection following PTA [36]. The role of primary stent placement has been revisited using nitinol stents. Second generation nitinol stents have spirally oriented interconnections, which have reduced rates of stent fracture and the resultant stenosis [37]. Recently, the RESILIENT trial demonstrated that primary deployment of self-expanding nitinol stents in moderate length femoral and popliteal lesions yielded better results than angioplasty alone [38]. Overall, studies examining the role of nitinol stents have yielded variable results, with moderate improvement in outcomes over PTA alone, and results varying significantly based on lesion specifics (TASC classification, lesions length, outflow vessel status) [39, 40].