INtimal hyPerplasia evAluated by oCT in de novo COROnary lesions treated by drug-eluting balloon and bare-metal stent (IN-PACT CORO): study protocol for a randomized controlled trial

Abstract

BackgroundNeointimal hyperplasia plays a pivotal role in the pathogenesis of in-stent restenosis in patients undergoing percutaneous coronary interventions. Drug-eluting balloons are a promising tool to prevent restenosis after coronary angioplasty. Moreover, an increased knowledge of the pathophysiology of restenosis my help improve therapeutic strategies.Methods/DesignWe present the design of an open-label, randomized three-arm clinical trial aimed to assess whether a strategy of bare-metal stent implantation with additional use of drug-eluting balloons, either before (pre-dilation) or after stenting (post-dilation), reduces the primary endpoint of in-stent neointimal hyperplasia area as compared with a strategy of bare-metal stent implantation alone. This primary endpoint will be assessed by optical coherence tomography at follow-up. Secondary endpoints will be the percentage of uncovered struts, and the percentage of struts with incomplete apposition. An ancillary study investigating the relation between systemic levels of endothelial progenitors cells and neointimal hyperplasia, and the interaction between endothelial progenitors cell levels and drug-eluting balloons has been planned. Thirty consecutive patients undergoing percutaneous coronary intervention will be randomized with a 1:1:1 design to bare-metal stent implantation alone (n = 10); bare-metal stent implantation after pre-dilation with a drug-eluting balloon (n = 10); or bare-metal stent implantation followed by post-dilation with a drug-eluting balloon (n = 10). Six-month follow-up coronary angiography with optical coherence tomography imaging of the stented segment will be performed in all patients. Blood samples for the assessment of endothelial progenitors cell levels will be collected on admission and at 6 months.DiscussionExperimental and early clinical data showed that inhibition of neointimal hyperplasia may be obtained by local administration of antiproliferative drugs loaded on the surface of angioplasty balloons. The INtimal hyPerplasia evAluated by oCT in de novo COROnary lesions treated by drug-eluting balloon and bare-metal stent (IN-PACT CORO) trial was conceived to test the superiority of a strategy of bare-metal stent implantation with additional drug-eluting balloon use (either before or after stenting) versus a strategy of bare-metal stent implantation alone for the reduction of neointimal hyperplasia. We also planned an ancillary study to assess the role of endothelial progenitors cells in the pathophysiology of neointimal hyperplasia.Trial registrationClinicaltrials.gov NCT01057563.

Atlas drug-eluting coronary stents inhibits neointimal hyperplasia in sheep modeling

“…Permanent polymers in drug-eluting stents used to overcome restenosis adversely affect the stented vascular restoration and prolong the inflammatory reaction process. Eventually, they contribute to late and very late thrombosis (9,18). When a biodegradable polymer is used, the drug is absorbed from the stent surface after elution, leaving only the neointima-and endothelium-coated metal stent without further irritating the arterial wall.…”

“…Although more invasive CABG is superior in some groups of patients, they have become the preferred methods of revascularization (4)(5)(6). On the other hand, reocclusion of the coronary arteries due to thrombotic occlusion in acute stages or neointimal hyperplasia (NIH) in the longer periods following minimally invasive techniques has been a major problem after MIT, particularly after bare metal stents (BMS) (7)(8)(9). In the longer period re-occlusion process, multiple factors such as smooth muscle cell (SMC) migration, activation of some cytokines and growth factors, extracellular matrix formation, neutrophil/macrophage activation are involved.…”

“…Drug-eluting stents (DES), which usually release sirolimus or paclitaxel, are now widely used to reduce the rate of restenosis (9). Compared to BMS, first-generation DES designed with nondegradable polymer coatings significantly reduced restenosis, but was associated with an increased risk of very late stent thrombosis.…”

Usability, safety, efficacy, positioning of the Atlas drug-eluting coronary stent: Evaluation of preliminary perioperative results

“…Drug-eluting stents (DES), which primarily release sirolimus or paclitaxel, are now widely used to reduce the rate of restenosis 10 . These stents are usually made of metal such as stainless steel or cobalt chrome alloy 14 .…”

Modeling Stented Coronary Arteries: Where We are, Where to Go

“…Among the current treatment options, angioplasty and stenting procedures are nowadays the preferred treatments due to their good clinical results and lower invasiveness compared to coronary artery by-pass. However, stenting success is still limited by some clinical issues affecting the arterial healing process such as neo-intimal hyperplasia, 9 in-stent restenosis 81 and late stent thrombosis. 86 These issues have been associated to arterial wall injury (rupture of the internal elastic lamina) during stent deployment 43 and other important biomechanical factors such as persistent nonphysiological stresses inside the arterial wall 26 or abnormal wall shear stresses (WSS) caused by a stentdisturbed hemodynamics that undermine the correct endothelial functionality.…”