Evolving DES Technology May Benefit Diabetic Patients
PARIS, France—The promise of new-generation DES for patients with diabetes was explored by 2 studies presented in a Hot Line session May 19, 2015, at EuroPCR.
One pitted a polymer-free stent against a permanent-polymer stent, while the other compared 2 new-generation DES.
Novel Device Aims to Improve Drug Release
For the RESERVOIR trial, Rafael Romaguera, MD, of Bellvitge University Hospital (Barcelona, Spain), and colleagues randomized 112 diabetic patients receiving glucose-lowering agents to receive an amphilimus-eluting stent (AES; n = 56) lacking a permanent polymer or to a conventional everolimus-eluting stent (EES; n = 56). Baseline characteristics were similar between groups, as was acute gain.
According to Dr. Romaguera, “amphilimus” is the name given to the combination of “sirolimus with an amphiphilic carrier, which modulates the elution [over 90 days], leaving then a bare-metal stent. The hypothesis of this trial was that, in addition to this, the fatty acid formulation would increase diffusion of sirolimus to the cardiac cell.”
The novel device met noninferiority criteria for the degree of neointimal volume obstruction (primary endpoint) compared with EES (mean 11.97% vs 16.11%; P for noninferiority = .0003); it did not show superiority (P = .22). Prespecified subgroup analysis showed an interaction between glucose control and treatment effect on the primary endpoint (P = .02), with the AES showing an advantage among patients with HbA1c levels above the median.
Both groups showed similarly “low” levels of uncovered and malapposed struts, Dr. Romaguera said. On paired QCA analysis of 102 lesions in 99 patients, mean in-segment minimal lumen diameter—but not in-stent—was larger in the AES group than in the EES group (2.09 vs 1.84 mm; P = .02). Values for percent diameter stenosis, whether in-stent or in-segment, did not differ by device.
At 12-months, clinical outcomes were statistically similar for AES- and EES-treated patients:
- Cardiac death: 1.8% vs 0%
- MI: 0% vs 1.8%
- Definite stent thrombosis: 0% vs 1.7%
- TLR: 5.2% vs 8.6%
- TVR: 5.2% vs 12.1%
- Target vessel failure: 6.9% vs 12.1%
- Unscheduled non-TVR: 10.7% in each group
“This is the first study to show noninferiority of a polymer-free, drug-eluting stent compared to a stent with the most robust evidence of safety and efficacy in diabetes,” Dr. Romaguera said. “It suggests that the antiproliferative drug formulated with an amphiphilic carrier [offers similar efficacy].”
However, he said, the results must be confirmed in a large RCT.
Asked by the session’s chairperson John Ormiston, MD, of Mercy Hospital (Auckland, New Zealand), to elaborate on the amphiphilic carrier, Dr. Romaguera described it as “long-chain fatty acids with hydrophobic bending and hydrophilic bending.”
In addition, panelist Jeffrey J. Popma, MD, of Beth Israel Deaconess Medical Center (Boston, MA), inquired whether the researchers had modeled how the drug would release, citing earlier experiences with reservoir-based stents that showed “tracking of where the drug would penetrate [or] diffuse.”
Unlike those devices, Dr. Romaguera countered, the current stent has reservoirs on both the luminal and abluminal sides. But, he added, no modeling has been done to isolate the differential effects of reservoirs compared with coated struts when using the same drug.
Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), told TCTMD in an email that the “study is interesting in that this new DES is polymer-free and has a special coating to promote healing—the stent elutes the drug via reservoirs and there is no polymer.” The current angiographic and IVUS findings, which she described as “excellent,” come on the heels of the stent already having shown low late loss comparable to what is seen with a first-generation device, she reported. “Now one needs to evaluate the safety and efficacy in a more complex patient and lesion population,” she said.
Second-Generation DES Compared
The second trial, OCT-DES, examined whether 2 DES that release different drugs result in similar vessel healing.
Presenter Stephen Hamshere, MBBS, of Barts Health NHS Trust (London, England), pointed out that after revascularization, patients with diabetes are at higher risk of mortality and morbidity—specifically stent thrombosis—compared with the general population. “Given that stent re-endothelialization is an important factor in the pathobiology of stent thrombosis and restenosis, it [stands out as] a sensitive surrogate measure,” he noted.
Dr. Hamshere and colleagues randomized diabetic patients treated at single center to receive standard PCI using the Promus Element (n = 29; Boston Scientific) or the Resolute Integrity (n = 30; Medtronic).
At 6 months, OCT data were available for 78% of the cohort. The percentage of uncovered struts (primary endpoint) was similar between the devices, as was the MACE rate. “This suggests comparable short-term outcomes between these 2 stent types,” Dr. Hamshere concluded.
“At times you said endothelialization, and at times you said strut coverage,” Dr. Popma said, asking for clarification on terminology. Dr. Hamshere replied that strut coverage was meant to signify the level of endothelialization.
“But how do you know they’re endothelial cells?” Dr. Popma stressed. “Forgive me, but we use these terms. Perhaps … we should just be talking about strut coverage.”
1. Romaguera R. A randomized comparison of reservoir-based polymer-free amphilimus-eluting stents versus everolimus-eluting stents in patients with diabetes mellitus: the RESERVOIR clinical trial. Presented at: EuroPCR; May 19, 2015; Paris, France.
2. Hamshere S. Comparison of 2 new-generation drug-eluting stents in patients with diabetes: the OCT-DES trial. Presented at: EuroPCR; May 19, 2015; Paris, France.
- RESERVOIR was funded by the Spanish Society of Cardiology, which has received an unrestricted grant from Biomenco.
- OCT-DES was funded by an unrestricted grant from Medtronic.
- Drs. Romaguera and Hamshere report no relevant conflicts of interest.