BOSTON — Despite a signal of potential superiority of the Cre8 EVO drug-eluting stent (DES) over the Resolute Onyx DES at 1 year post-percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM), the 2-year results failed to show superiority of the new DES.
Pablo Salinas, MD, PhD, of Hospital Clínico San Carlos, Madrid, presented these findings from the SUGAR trial Monday at Transcatheter Cardiovascular Therapeutics (TCT) in Boston.
PCI in DM has an increased risk of adverse events; however, few studies have been conducted specifically in the population.
The Cre8 EVO stent (Alvimedica) is a thin-strut (70-80 μm), polymer-free stent that elutes amphilimus, a formulation of sirolimus and a fatty acid carrier, from laser-dug wells. This formulation enhances drug intake by the endothelial cells, Salinas explained.
Improved outcomes, specifically less restenosis, were found with the Cre8 EVO stent in non-randomized or small randomized trials of DM patients.
SUGAR (Second-generation drug-elutingG stents in diabetes: a Randomized trial) aims to determine whether these findings can be confirmed. It randomized 1,175 all-comer patients with DM eligible for PCI 1:1 to receive either Cre8 EVO stent or the Resolute Onyx durable-polymer stent (Medtronic) with 92-102 μm struts eluting zotarolimus.
The primary endpoint was TLF, a composite of cardiac death, target vessel myocardial infarction or target lesion revascularization.
The 1-year results, presented at TCT 2021, showed that the Cre8 EVO stent met the primary endpoint for noninferiority to the Resolute Onyx stent in terms of TLF (Cre8 EVO 7.2% vs. Resolute Onyx 10.9%), and a prespecified exploratory analysis suggested that the Cre8 EVO stent might even be superior (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.44-0.96; p=0.03), which caused a great deal of fanfare at the time.
At 2 years, however Cre8 EVO failed to meet the primary endpoint for superiority to the Resolute Onyx stent in terms of TLF (HR 0.84; 95% CI: 0.60-1.19; p=0.331), even though the TLF rates were still similar between the two devices (Cre8 EVO 10.4% vs. Resolute Onyx 12.1%).
The two stents also showed similar results in relevant secondary outcomes: cardiac death (3.1% vs. 3.4%; HR 0.81; 95% CI 0.42-1.55; p=0.519), target vessel myocardial infarction (6.6% vs. 7.6%; HR 0.89; 95% CI 0.56-1.42; p=0.627), target lesion revascularization (4.3% vs. 4.6%; HR 0.93; 95% CI 0.54-1.60; p=0.782), all-cause mortality (7.1% vs. 6.8%; HR 1.03; 95% CI 0.67-1.59; p=0.89), all subsequent revascularizations (7.6% vs. 9.4%; HR 0.79; 95% CI 0.54-1.19; p=0.265), and major adverse cardiac events (18.3% vs. 20.8%; HR 0.88; 95% CI 0.68-1.16; p=0.371).
Although there was insufficient evidence to show superiority of the Cre8 EVO stent, Salinas said extended follow-up through 5 years is still warranted.
In response to questions during a TCT press conference, Salinas said the Cre8 EVO stent’s events accrued in a “slow but steady” fashion, while the Resolute Onyx stent’s events were clustered in the first 6 months and then slowed down significantly.
Carlo Di Mario, MD, of Careggi University Hospital, Italy, a panelist during the press conference, remarked that while the disappearance of the Cre8 EVO’s advantage might be a “bitter note,” it “is not bitter for us because overall, the percentages of figures are so low that it is rather difficult to find a difference” between the stents.
Roxana Mehran, MD, of the Icahn School of Medicine at Mount Sinai, New York, commended the SUGAR trialists for continuing to follow the patients beyond the 1-year positive results.
“You could have stopped at 1 year and been very, very happy with your positive result and walked away,” she said. “And I really want to congratulate you for your transparency and following these patients up because we as clinicians need answers for our diabetic patients.”
The SUGAR trial was funded by the Spanish Society of Cardiology.
Image Credit: Jason Wermers/CRTonline.org