“Anti‐healing” versus “pro‐healing”

The Drug Eluting Stent (DES) has revolutionized the treatment of obstructive and symptomatic coronary artery disease by decreasing restenosis. It is gratifying to see complex and multiple lesions, long lesions in small vessels, bifurcation lesions, and total occlusions looking ‘‘pristine and frozen in time’’ even years after DES implantation—which we rarely saw in Bare Metal Stent (BMS) era 10 years ago. However, the initial ‘‘mass euphoria’’ of 0% restenosis in the RAVEL study has sobered down over the last six years as we keep encountering a new set of complications in our daily practice—that occasional patient with aneurysmal dilatation at the site of DES implantation; the patient who discontinues dual antiplatelet therapy two years later for a noncardiac surgery and has an acute MI; worse still, a patient who four years after DES implantation has extremely late stent thrombosis (VLST) and MI despite continuing dual antiplatelet therapy. While debates, with evidence and counter evidence, rage regarding the long-term safety of DES, we all realize that a small and definite risk of sudden and unforeseen VLST continues to remain with our patients for years following DES implantation. We are no more overjoyed; we wish we could do things differently and are looking for answers? VLST following DES is an interplay of numerous factors: procedure and operator-related, lesion-related, patient-related, antiplatelet therapy-related, stentand polymer-related. But the most consistently and persistently prevalent factor is the ‘‘anti-healing’’ property of DES. Following intimal vascular injury due to stent implantation, the nature heals the vessel wall by reforming a robust and functional endothelium covering the stent and the injured segment. Sirolimus and Paclitaxel while suppressing smooth muscle cell migration and neointimal proliferation to decrease restenosis, also suppress endothelial cells and inhibit re-endotheliazation. They are therefore ‘‘anti-healing’’. The nonendothelized stent struts could predispose to thrombosis even many years later [1]. For the same reason, newer generation of DES using different ‘‘anti-healing’’ drugs, irrespective of new polymer or stent platforms, would continue to create similar safety concerns over many years till proven otherwise. In this issue of CCI, Miglionico et al. publish their experience of a novel and radically opposing approach; ‘‘pro-healing’’ using endothelial progenitor cell (EPC) antibody coated Genous R Stent (Orbus Neich, Fort Lauderdale, Florida). This stainless steel bio-engineered stent is coated with antibodies specific to CD34 and thus captures the circulating EPCs derived from bone marrow. The EPCs are responsible for natural intimal healing and accelerate the process of re-endotheliazation over the stent thus providing protection against thrombosis as well as hopefully decreasing restenosis. In this single center prospective registry, 93 Genous R Stent were implanted in 80 patients who were at high risk for stent thrombosis or restenosis. Majority patients received dual antiplatelet therapy for 2 months only. Over a mean follow up of 14 months, there was no stent thrombosis. The 8-month angiographic restenosis rate in prospectively defined 31 patients subgroups was 19% and late loss was 0.88 mm—although only 5% of patients had ischaemia driven TLR. Keeping in mind the relatively large vessels treated (mean reference vessel diam: 3.3 mm) and that two third patients had 18 mm stents; the results of this relatively small registry may not look impressive. Other perspective registries using the Genous R stent have demonstrated excellent safety profile in the intermediate term with low TLR’s. The HEALING II Study (Healthy Endothelial Accelerated Lining Inhibitors Neointimal Growth) enrolled 63 patients in 10 European Centers who received Genous R stent followed by one month of dual antiplatelet therapy. The mean lesion length was 9.83 mm. The 9 month TLR (6.3%) and MACE (7.9%) was unchanged at 18 months. There was no sub acute or late stent thrombosis. Interestingly there was a regression of late