Developments in the percutaneous treatment of obstructive coronary artery disease

Abstract

Percutaneous coronary interventions are recognized techniques to treat coronary artery disease. However, despite the progress in the development of materials and techniques, several limitations affect the acute and long-term performance of these procedures. In particular, there are three mayor drawbacks: restenosis, thrombosis and technical feasibility of the procedure. The recent introduction of drug-eluting stents has been a major step forward in reducing restenosis. The pivotal randomized trials versus bare metal stents, performed in selected patients and lesions, showed a dramatic reduction in restenosis rate with extremely low rates in the drug-eluting stent group. However, a potential issue related to the possibly increased incidence of stent thrombosis with these new devices appeared. Our thesis had two major aims: 1) to assess the values and drawbacks of first-generation drug-eluting stents (eluting sirolimus or paclitaxel) when used in patients and lesions not included in the pivotal trials, and 2) to assess new drug-eluting stents and stents specifically dedicated for selected anatomies. We showed in different subsets of patients and lesions that first-generation drug-eluting stents achieve good results also in off-label indications, such as in left main coronary artery disease, in saphenous vein graft disease, and in “real-life” “daily-practice” unselected patients. However, restenosis appeared still to be an issue specifically in the treatment of distal left main disease, in diabetic patients, and in patients in whom multiple lesions or long stents were placed. Moreover, in the treatment of saphenous vein graft disease, we showed an alarming increase in mortality at long-term follow-up with drug-eluting stents as compared to bare metal stents, finding mainly driven by potential thrombotic events occurring after placement of these new devices. As we showed that first-generation drug eluting stents were not free from complications, the search for new drugs and new stent designs appeared crucial in order to further improve the outcomes of percutaneous coronary interventions. First, we focused our research on a new anti-restenotic drug, pimecrolimus, that provided promising results in further reducing restenosis in animal models. We tested this new drug directly loaded onto a stent. However, pimecrolimus-eluting stents failed to fulfill in humans its preclinical promises as anti-restenotic drug. Finally, we focused on two novel self-expanding drug-eluting nitinol stents, one eluting biolimus and designed for bifurcation lesions, the other eluting sirolimus, designed for small vessels and directly loaded into a 0.014 inches coronary guidewire. The first stent showed to be highly deployable and it provided very interesting results with low angiographic and clinical restenosis rates in a difficult setting such as the one of bifurcations. We then described the case of a patient with a lesion in a small vessel, successfully treated with the stent directly loaded into the coronary guidewire. This stent with its extremely low-profile (the same as a routine coronary wire) has the potential to become a major step forward in tackling complex anatomies with extremely tortuous vessels and lesions located in the distal vasculature, where other “traditional” stents would not be able to be tracked.