Introduction

Endovascular treatment for peripheral arterial disease (PAD) was first described by Dotter and Judkins in 1964. Since then, restenosis formation has been the greatest enemy of endovascular therapy.

Many different devices and techniques have been introduced over the last 60 years, including angioplasty balloons and self-expanding nitinol stents. Still, neointimal hyperplasia, respectively, and restenosis remain the main problems preventing long-term patency and freedom from reintervention (TLR). In 1996, the Dutch group of Ozaki et al. published a paper about new stent technologies, and they formulated the following approach: “Finally, the problem of persisting induction of intimal hyperplasia may be overcome with the use of … a stent eluting an antiproliferative drug” [1]. After successfully introducing coronary drug-eluting stents (DES), the first attempts for drug-eluting femoropopliteal stents failed to show superiority over standard techniques. Dake et al. were the first who could prove the superiority of the drug-eluting concept with a paclitaxel-coated nitinol stent [2]. However, it could be shown that extensive and circumferential vessel calcifications are associated with lower patency and a higher rate of TLR in the use of the Zilver PTX™ (Cook Medical®) [3]. Similar results could be obtained for drug-coated balloons (DCB) [4]. So, it seems like calcium is the natural enemy of paclitaxel and the drug-eluting therapy.

In the present publication, Gouveia e Melo et al. observed that the presence of severe calcifications did not influence the primary patency of the treated vessels after Eluvia™ (Boston Scientific®) DES deployment [5]. Is that a contradiction to the existing data, or can it be explained by the stent design? Both stents, Eluvia™ and Zilver PTX™, are composed of a laser-cut nitinol scaffold covered on the outside with the antiproliferative drug (paclitaxel). The main difference between both stents is a so-called excipient (polymer coating) between stent struts and the hydrophobic drug in the Eluvia™ stent. So, an apparent explanation for the encouraging outcome of the Eluvia™ stent in heavily calcified lesions might be the excipient that facilitates the paclitaxel to migrate into the vessel wall, a factor that is not present in the Zilver PTX™ stent. On the other hand, all DCBs have an excipient between the balloon surface and the drug, but presumably, the time for drug migration through calcified lesions is too short.

Notably, the two-year primary patency in the patients of the present study was 71%, similar to a two-year primary patency in the Japanese Zilver PTX™ post-market surveillance study of 70.3% [6]. Nevertheless, the superiority of DES over bare stents in terms of patency and freedom of TLR is beyond question, and I strongly believe that we are committed to offering our patients the best possible treatment. Therefore, the present study is important for the decision-making process in treating challenging femoropopliteal lesions.

Other options to overcome the problems of severely calcified lesions are atherectomy and intravascular lithotripsy (IVL). The combination of atherectomy and DCB has been extensively studied, showing similar results compared to DCBs alone with fewer complications as dissections. However, there is only little evidence for the combination of atherectomy and DES. Very promising seems to be the implementation of IVL in the therapy of heavily calcified peripheral lesions. CIRSE endorses the newest research project, CALCIO, CIRSE's first venture into endovascular research. CALCIO stands for “chronic limb-threatening ischemia treated with intravascular lithotripsy observational study.” The principle of IVL is to deliver shock waves within calcified vessels to break calcium deposits, thereby softening the calcified plaque and potentially improving the outcome of subsequent endovascular treatments.

Calcium is an independent risk factor for loss of patency and clinical failure in endovascular revascularization with or without the use of drug-eluting devices. So, calcium is not only the natural enemy of drug-eluting therapy but also the natural enemy of endovascular therapy in general. Already, Aristoteles knew that it takes more than a swallow to make a summer, but the results of the present study are very encouraging and will hopefully soon be confirmed by more data.