Ultrathin Stent Holds Its Own in High-Bleeding-Risk Patients: COMPARE 60/80

SAN FRANCISCO, CA—In a battle of the skinny versus the skinnier, the COMPARE 60/80 study has shown that an ultrathin stent performed just as well as a conventional thin-strut stent in a cohort of patients at high risk for bleeding.

While investigators demonstrated the ultrathin-strut stent (Supraflex Cruz; SMT) was noninferior to a slightly-thicker-strut technology (Ultimaster; Terumo), it did not beat the thin-strut stent when it came to net adverse clinical events (NACE) or other endpoints in this relatively small trial.

Presentation TCT 2023

The Primary Endpoint Results from the COMPARE 60/80 HBR Trial: A Randomized Controlled Multi-Center Trial Comparing Ultrathin With Thin Strut Stents in High Bleeding Risk Patients With an Abbreviated DAPT Duration

Lead investigator Pieter Smits, MD, PhD (Maasstad Hospital, Rotterdam, the Netherlands), who presented the results at TCT 2023, said he wasn’t disappointed by the absence of superiority, telling the media the study goal was to show the ultrathin-strut stent was equivalent to the thin-strut Ultimaster stent platform.

“It is important for us in the changing landscape of shortening DAPT [dual antiplatelet therapy], especially in high-bleeding-risk patients, to have more evidence and more stents available that are safe and effective,” he said. “For me, it’s another stent with proven evidence.”

Both devices used in the trial were biodegradable-polymer sirolimus-eluting stents. The major difference between the two is the Supraflex Cruz stent has struts that are 60-μg thick whereas the Ultimaster device has a strut thickness of 80 μg.

Ultrathin-strut stents, which are defined as those measuring 70 μg or less, have been shown to be “less thrombogenic, less traumatic to the vessel wall, [provide] more rapid endothelialization, and [lead to] less intimal hyperplasia” when compared with thicker stents, said Smits. In a meta-analysis of trials pitting ultrathin-strut stents against second-generation DES, investigators showed that the ultrathin technology was associated with less target lesion failure after 2.5 years of follow-up, a benefit driven by less target lesion revascularization.

‘Enriched’ Patient Population

Like other studies in high-bleeding-risk patients, the 732 individuals randomized in COMPARE 60/80 were elderly (mean age 75 years; 73% men) and nearly one third had diabetes. Approximately 70% were treated for chronic coronary syndromes. Imaging, either with IVUS or optical coherence tomography (OCT) before or after the procedure, was performed infrequently: IVUS was used in a little more than 3.5% of cases and OCT in just over 1% of procedures. The mean duration of DAPT was 30 days.

“Our hypothesis was that the benefits of the ultrathin-strut DES might be enhanced in a high-bleeding-risk PCI population with shortened DAPT,” said Smits.

The NACE endpoint—a composite of cardiovascular death, MI, target vessel revascularization, stroke, and major bleeding—occurred in 17.1% of patients treated with the thin-strut stent and 15.4% of those treated with the ultrathin-strut stent (HR 0.89; 95% CI 0.62-1.28), which met the noninferiority margin of 4.0%. There was no difference in any of the secondary endpoints, but MIs and target vessel revascularizations, as well as target lesion revascularizations, were numerically fewer with the ultrathin-strut stent. There was no difference in the risk of definite/probable stent thrombosis.

A larger study will be needed to show the ultrathin-strut Supraflex Cruz stent can further improve outcomes of PCI patients, said Smits.

It’s another stent with proven evidence. Pieter Smits

To TCTMD, Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), who moderated the late-breaking clinical trial session, said neither stent is commercially available in the US, although the Ultimaster device does have CE Mark approval in Europe. The trial, he said, was “innovative” in that by taking on patients at high bleeding risk treated with a shorter duration of DAPT, investigators reduced the number needed to be enrolled to achieve noninferiority.

Duk-Woo Park, MD (Asan Medical Center, Seoul, Republic of Korea), who commented on the study following the late-breaking presentation, also pointed out that COMPARE 60/80 was two-to-three times smaller than other PCI trials. BIOFLOW-DAPT, for example, enrolled close to 2,000 high-bleeding-risk patients. He questioned the comparator stent chosen for this trial, noting that a number of different stents have been used in the host of studies over the past 5 years testing shortened DAPT.

“Many, many contemporary drug-eluting stents could work in the [high-bleeding-risk] population with abbreviated DAPT duration,” said Park.

In response, Smits said the Ultimaster thin-strut stent was chosen because it was used in the MASTER DAPT trial showing that 1 month of DAPT was safe and effective when compared with standard DAPT (at least 3 months) in patients at high risk for bleeding.

Panelist Margaret McEntegart, MD, PhD (NewYork-Presbyterian/Columbia University Irving Medical Center), said that from a “philosophical” perspective, she was surprised by the lack of imaging in a study trying to tease out differences between stents where strut thickness varied by just 20 μg. She countered that more widespread use of imaging rather than scaling back stents might be a better way to reduce the risk of adverse outcomes. Smits said the study reflects current European practice where imaging is used in just 5% to 10% of cases. “That’s the reality,” he said. “In a setting where you don’t have the ability to use intravascular imaging in a high percentage [of cases], I think the choice of stent becomes potentially more important.”

Robert Byrne, MBBCh, PhD (Mater Private Network, Dublin, Ireland), asked whether there could be a downside to thinner and thinner struts, but said he was reassured by the angiographic substudy that showed there was no difference in acute gain between the two stents. “We didn’t seem to be losing anything with these very thin struts,” said Byrne.

To TCTMD, Kirtane said that an ultrathin device would ultimately need to be tested in heavily calcified lesions to determine if it’s possible to be “too thin.” In that setting, greater radial strength is needed, but in a trial like COMPARE 60/80, it’s difficult to discern if there’s a downside to these ultrathin-strut devices, he said.

As for whether the market needs another stent, Kirtane said it could be argued that devices used for routine, daily use are somewhat interchangeable, but that having more commercially available stents tends to help exert pressure on price.