Anecdotal vs. evidence-based, off label use of drug eluting stents for infrapopliteal disease: Abusus non tollit usum (Misuse does not nullify proper use)

Abstract

As the rates of adverse events associated with infrapopliteal balloon angioplasty, atherectomy, and stenting have dropped and relative success rates have increased in recent years, the desire to offer endovascular treatment to patients with limb threatening ischemia and disabling claudication as an alternative to distal bypasses has become widespread. Occlusive disease of the tibial vessels, once felt to be optimally treated with operative bypass only is now increasingly being treated percutaneously [1-6]. Nevertheless, results of operative arterial reconstruction have also considerably improved. Excellent outcomes following bypass grafting with vein graft to the pedal vessels have been demonstrated, with morbidity, mortality, and long-term patency comparable to that of more proximal bypasses. Within the context of a changing paradigm, it is an appropriate time to examine and potentially redefine the role of both endovascular and open surgical intervention for patients with infrageniculate arterial occlusive disease. Traditionally, infrapopliteal disease treatment was reserved for patients with nonhealing ulcers and critical limb ischemia (Rutherford 4–6, Fontaine II–III) since the extensive collateral network often can provide enough perfusion in the presence of intact skin to maintain tissue viability. This management strategy was dictated by the often diffuse calcific nature of the disease and the prohibitively low intermediate and long-term patency rates of various percutaneous therapies. However, revascularization is indicated in at risk limbs to provide improved straight-line, arterial pulsatile flow for successful healing and limb salvage. In many cases, surgical techniques are not appropriate because of the debilitated general medical condition or myriad comorbidities that are often present in this patient cohort. Furthermore, surgery may not be feasible due to the lack of suitable distal outflow vessels or the absence of venous conduit. Therefore, interventional endovascular techniques are increasingly used for below-the-knee lesions in patients with critical limb ischemia (CLI). The promising acute success rates have been tempered by low intermediate and long-term patency rates. Nevertheless, these therapies still provide adequate tissue healing and limb salvage. A number of adjunctive therapies including Excimer Laser, Cryoplasty, Atherectomy, and bare metal and drug eluting stent (DES) are all used in this patient population, though none of these techniques are associated with definitive superiority compared with bypass surgery—as is the case for many peripheral interventional procedures [4, 5, 7-12]. The authors report, in this issue, on their use of 17 DES in 12 below-knee vessels (10 patients) with a mean stent length or 38.3 mm. The length of treatment reflects the diffuse nature of the disease. They achieved success in all patients with one episode of stent thrombosis at 3 weeks, and 10% TVR at 12.4 ± 6.5 months. This report adds to the previous literature describing the use of DES in infrapopliteal revascularization, [5, 6, 10] with improved patency rates and lower TVR, but without demonstrable clinical benefits in terms of limb salvage and minor amputations, compared with angioplasty or bare metal stents [5, 6, 10] However, the concerns voiced over DES use in the coronary circulation have to affect this practice that is substantially “off-label”, [13, 14] with increased cost (stents and ensuing longer-term dual antiplatelet use). In addition, the diffuse and calcified nature of infrapopliteal disease might necessitate longer and smaller stent use, thus increasing risk of thrombosis with the intermittent low flow rates and the differing arterial biology that is present in the peripheral vasculature compared with the coronary circulation. Therefore, the primary concern of infrapopliteal revascuscularization should be to reestablish flow and achieve an “adequate” acute result. An angiographically pleasing result does not necessarily translate into a meaningful clinical outcome. If this angioplasty results in significant dissection, then bare metal (self expanding, or balloon expandable) stents may be preferable. DES could then be restricted to treat restenosis if further treatment is indeed necessary. Furthermore, not all infrapopliteal disease is the same; targeted therapy with various available devices tailored to the observed disease (calcification, eccentricity, length, bifurcations, collateral supply, etc.) with balloon angioplasty being the mainstay of revascularization whenever possible. Finally, DES specifically designed for the periphery should be developed (and are currently in development) with probable design changes (to prevent fracture) and different delivery characteristics to fit level of flow. Randomized studies and careful registries should be the only gateway for testing newer and more expensive devices in peripheral vascular disease, in general, and for infra-inguinal disease in particular. We should demand the same level of evidence that has been applied to coronary disease treatment. Expansion of our knowledge base to better guide the proper utilization of devices and techniques may indeed be the greatest contribution of the current era of vascular specialists.