Despite a promising start, extended follow-up from the SUGAR trial found that the Cre8 EVO drug-eluting stent could not maintain superiority over the Resolute Onyx DES at 2 years in patients with diabetes undergoing revascularization for coronary artery disease.
The Cre8 EVO stent (Alvimedica) is not available in the US but, as previously reported, caused a stir last year after demonstrating a 35% relative risk reduction in the primary endpoint of target lesion failure (TLF) at 1 year in a prespecified superiority analysis.
At 2 years, however, the TLF rate was 10.4% with the polymer-free Cre8 EVO amphilimus-eluting stent and 12.1% with the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent, which did not achieve superiority (HR, 0.84; 95% CI, 0.60 – 1.19).
Rates were numerically lower with the Cre8 EVO stent for the endpoint’s individual components of cardiac death (3.1% vs 3.4%), target vessel MI (6.6% vs 7.6%), and target lesion revascularization (4.3% vs 4.6%).
Results were also similar between the Cre8 EVO and Resolute Onyx stents for all-cause mortality (7.1% vs 6.8%), any MI (9.0% vs 9.2%), target vessel revascularization (5.5% vs 5.1%), all new revascularizations (7.6% vs 9.4%), definite stent thrombosis (1.0% vs 1.2%), and major adverse cardiac events (18.3% vs 20.8%), Pablo Salinas, MD, PhD, of Hospital Clinico San Carlos, Madrid, Spain, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2022.
He noted that all-cause mortality was 7% in just 2 years in the diabetic cohort, or twice the number of cardiac deaths. “In other words, these patients had the same chance of dying from cardiac causes and noncardiac causes, so we need a more comprehensive approach to the disease. Also, if you look at all new revascularizations, roughly 50% were off target, so there is disease progression at 2 years in this population.”
Among the 586 Cre8 EVO and 589 Resolute Onyx patients who underwent percutaneous coronary intervention (PCI), roughly half had multivessel coronary artery disease, 83% had hypertension, 81% had dyslipidemia, and 21% were current smokers. Nearly all patients had diabetes type 2 for an average of 10.6 years for Cre8 EVO and 11.4 years for Resolute Onyx, with an A1c level of 7.4% and 7.5%, respectively.
Although there is “insufficient evidence” the Cre8 EVO stent is superior to the Resolute Onyx stent with regard to TLF, Salinas concluded extended follow-up until 5 years is warranted.
During a discussion of the results, Salinas said he expects the 5-year results will “probably go parallel” but that it’s worth following this very valuable cohort. “There are not so many trials with 1000 diabetic patients. We always speak about how complex they are, the results are bad, but we don’t use the diabetic population in trials.”
Asked during a TCT press conference what could have caused the catch-up in TLF at 2 years, Salinas said there were only 25 primary events from years 1 to 2, driven primarily by periprocedural MI, but that the timing of restenosis was different. Events accrued “drop by drop” with the Cre8 EVO, whereas with the Resolute Onyx there was a “bump in restenosis” after 6 months “but then it is very nice to see it is flat, which means that durable polymers are also safe because we have not seen late events.”
Press conference discussant Carlo Di Mario, MD, from Careggi University Hospital, Florence, Italy, who was not involved in the study, said the reversal of superiority for the Cre8 EVO might be a “bitter note” for the investigators but “maybe it is not bitter for us because overall, the percentage of figures are so low that it’s very difficult to find a difference” between the two stents.
Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York City, who previously described the 1-year results as “almost too good to be true,” commented to theheart.org | Medscape Cardiology, “We just saw in this trial, no benefit whatsoever at 2 years in terms of target lesion failure. So it’s very important for us to evaluate this going forward.”
She continued, “We’ve always been talking about these biodegradable polymers and then going back to the bare metal stent, oh that’s great because polymers aren’t so good, but now we’re seeing durable polymers may be okay, especially with the current technology.”
Asked whether Cre8 EVO, which is CE mark certified in Europe, remains an option in light of the new results, Mehran said “I don’t think it kills it. It’s not worse, it’s another stent that’s available.”
Nevertheless, “what we’re looking for is some efficacious benefit for diabetic patients. We don’t have one yet,” observed Mehran, who is leading the ABILITY Diabetes Global trial, which just finished enrolling 3000 patients with diabetes and is testing PCI with the Abluminus DES+ sirolimus-eluting stent system vs the Xience everolimus-eluting stent. The study is estimated to be complete in August 2024.
The study was funded by the Spanish Society of Cardiology. Salinas reported consulting fees/honoraria from Boston Scientific, Abbott Vascular, Biomenco, and Medtronic.
Transcatheter Cardiovascular Therapeutics (TCT) 2022. Presented September 19, 2022.
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