PARIS – Interventional cardiologists are hopeful that a new generation of investigational coronary stents designed specifically for use in diabetes patients will improve upon the relatively poor current outcomes of percutaneous coronary intervention in that population.
The operative word here is “abluminal.” Both of the novel drug-eluting stents featured at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions position their antirestenosis drugs abluminally: that is, aimed toward the vessel wall surface, not the lumen.
“The hypothesis is that Luca Testa, MD, PhD, head of the coronary revascularization unit at San Donato Hospital in Milan.,” explained
There is a major unmet need for improved stent technology that addresses the special needs of diabetes patients, who tend to have more diffuse and rapidly progressive coronary artery disease (CAD) with longer lesions. Target lesion revascularization rates at 5 years of follow-up in diabetes patients with current generation drug-eluting stents (DES) remain high, at 20% or more. And diabetes patients are roughly 3.5-fold more likely to have nonfocal, diffuse coronary lesions than are nondiabetic patients with CAD, the cardiologist noted.
The sense of urgency surrounding this unmet need stems from the ongoing worldwide epidemic of diabetes. The global prevalence of diabetes was estimated at 382 million in 2013 and is projected to climb to nearly 600 million by 2035. Diabetes patients are two to four times more likely to develop CAD than are those without the disease. Because of the current suboptimal results with percutaneous coronary intervention (PCI), many of them are being referred for coronary artery bypass surgery.
Dr. Testa presented the 1-year results of the ongoing en-ABL e-Registry, a 5-year, multicenter, prospective, all-comers registry of 859 diabetic and 1,641 nondiabetic CAD patients who received the Abluminus DES at 31 centers in India. The novel stent, developed by Envision Scientific of India, is coated with sirolimus on the abluminal side. The device is actually both a DES and a drug-coated balloon. The balloon, including its proximal and distal ends, are also sirolimus coated to maximize exposure of diseased artery to the drug. The balloon needs to be inflated in position for at least 30 seconds to deliver its portion of sirolimus. The stent is composed of a biodegradable polymer matrix that is metabolized within 6-8 months.
The primary endpoint at 1 year of follow-up was the composite of cardiac death, target vessel MI, and target lesion or vessel revascularization. The rate was 3.12% in the diabetic population, which wasn’t significantly different from the 2.1% rate in nondiabetic patients. Of note, the rate was 5.17% in the 138 insulin-dependent diabetes patients, compared with 2.76% in 721 non–insulin-dependent patients.
Among diabetes patients, the composite endpoint occurred in 2.82% of those who underwent primary PCI with the Abluminus DES for an acute MI, 3.96% of those treated for lesions in small vessels 2.75 mm or less in diameter, 3.75% in diabetes patients treated for long lesions, and 4.18% in the subgroup with long lesions in small vessels.
On the basis of these encouraging results, Dr. Testa has been named the principal investigator for the new prospective, multicenter, observational DEDICATE registry, restricted to diabetic patients treated with the Abluminus DES.
Also getting underway is a randomized, investigator-initiated, multicenter, single-blind pilot study involving 165 diabetes patients assigned 2:1 to the Abluminus DES or the Xience everolimus-eluting stent, widely considered the current gold standard DES. The study, known as the ABILITY trial, has as its primary endpoint the in-stent neointimal volume as measured by optical coherence tomography 6 months post PCI. The medical director of the study is Antonio Colombo, MD, director of the cardiac catheterization laboratory and the interventional cardiology unit at San Raffaele Hospital in Milan.
Elsewhere at EuroPCR 2018, officials at Alvimedica Medical Technologies announced that the company’s abluminal stent, known as the Cre8 EVO, will be pitted against the everolimus-eluting stent in a 55-center trial of 3,040 diabetes patients. The hypothesis of the Diab8 trial, based on preliminary data from pilot studies, is that the abluminal stent will show clinical superiority – not merely equivalence – at 1 year.
The Cre8 EVO stent utilizes a proprietary, polymer-free, drug-release technology involving reservoirs located on the stent’s outer surface that direct the controlled release of a mixture of sirolimus and fatty acids that the company calls the amphilimus formulation. The drug mixture is designed to enhance tissue permeation and sirolimus bioavailability. The body of the stent is cobalt, which was used based upon a conviction that polymers are more proinflammatory.
Dr. Colombo is also the principal investigator of the Diab8 trial, sponsored by Alvimedica.
Dr. Testa reported having no financial conflicts regarding his work on the en-ABL e-Registry, funded by a nonprofit Italian cardiovascular research foundation.