Balking at Bulk: SORT-OUT VIII Hints at Clinical Edge for Thinner-Strut Stents

PARIS, France—The latest SORT-OUT trial to pit two commercially available drug-eluting stents against one another in routine care suggests that the cobalt-chromium, everolimus-eluting Synergy stent (Boston Scientific) is noninferior to the stainless-steel, biolimus-eluting BioMatrix NeoFlex stent (BioSensors), but the former’s thinner struts appear to have given it the edge in terms of deliverability.

That enhanced deliverability may also explain a signal of fewer MIs and fewer “patient-centered events,” said Michael Maeng, MD (Aarhus University Hospital, Denmark), who presented SORT-OUT VIII during a late-breaking session at EuroPCR 2018.

The large, randomized trial results are in keeping with several other presentations here which also hint that enhanced deliverability with newer, thin-strut devices may pay off in terms of repeat cardiac events down the road.

Both the NeoFlex and the Synergy are commercially available in Europe—only the Synergy is available in the United States—and importantly both boast bioresorbable polymers. Where they differ is in their base material and strut thickness, which is 81 μm for Synergy and 112 μm for NeoFlex.

SORT-OUT VIII

The 2800-patient, investigator-initiated SORT-OUT VIII trial enrolled an “all-comers” population, randomizing patients to one of the two stents and then following them for 1 year. More than half of the patients in the trial were treated for ACS and nearly one in five had had a previous MI. Fewer than 25% were female and the mean age was 67 years.

The primary endpoint of target lesion failure (cardiac death, target lesion MI, or target lesion revascularization) within 12 months occurred in 4.0% of Synergy-treated patients and 4.4% of NeoFlex-treated patients, meaning that Synergy met criteria for noninferiority (P < 0.001) but not for superiority (P = 0.57).

There were no significant differences in the rates of stent thrombosis or a range of other secondary endpoints related to the target lesion or target vessel. Device delivery failure, however, was more common with the NeoFlex than the Synergy (1.8% vs 3.0%, P = 0.044). Rates of “any MI” were also higher in the NeoFlex group (1.9% vs 3.4%; HR 0.56; 95% CI 0.35-0.91). The latter was a key driver of the difference in the “patient-related composite endpoint” of all-cause mortality, any MI, or any clinically driven revascularization (11.2% vs 13.6%; HR 0.80; 95% CI 0.65-1.00).

“Successful implantation of the allocated stent was more frequent in the thin-strut Synergy group, which may be associated with the lower rate of MI and the patient-related composite endpoint,” Maeng concluded.

Deliverability and Clinical Events?

During the discussion following SORT-OUT VIII’s presentation, panelist Manel Sabaté, MD, PhD (Institut Clínic Cardiovascular, Barcelona, Spain), took issue with Maeng’s conclusion, pointing out that a thicker stent strut is unlikely to be the cause of an MI occurring in another vessel, saying “it would affect target vessel MI only,” he said.

Maeng countered, saying, “The thing is, if you have a stent that is more difficult to implant, you may be more aggressive with the guiding catheter, you might be more aggressive about using . . . guidewires to get the stent down, because we really tried to go with the allocated stent, not to change the stent. So that may be an explanation, but it is purely speculative.”

Commenting on the study for TCTMD, Julinda Mehilli, MD (Munich University Clinic, Germany), said that the results were “not a surprise.”

“The BioMatrix device is a thick-strut stent and the thickness of the struts causes many problems. You can have reinterventions, MI, side branches that you close during the procedure; you have difficulty putting the stent in, so there are technical problems.”

All of these things are known to be pitfalls of bulkier, earlier-generation devices, she continued. In current practice, the only time she will opt for a stainless-steel device is for ostial lesions or very calcified lesions, “in which you can have a lot of recoil with the cobalt-chromium devices.”

According to Mehilli, physicians are no longer worried about restenosis, since all of the current devices have low restenosis risk. “Xience (Abbott), Synergy, Ultimaster (Terumo), Orsiro (Biotronik)—these are all thin-strut stents, easy to place, they do less damage, and they are superior to thick-strut stents,” she said. As such, the SORT-OUT VIII results confirm what many people already believed, she concluded, that the new “family” of thin-strut stents are likely better than the old ones.

Indeed, in a separate presentation during a Wednesday late-breaking session, Floris Kauer, MD, PhD (Albert Schweitzer Hospital, Dordrecht, the Netherlands), presented a propensity-matched analysis of two international registries to address the relative safety and efficacy of the 80-μm, sirolimus-eluting Ultimaster stent and the 120-μm, biolimus-eluting Nobori stent (Terumo). Noting the limitations of the nonrandomized comparison, Kauer nevertheless concluded that rates of MI, TLF, and TVR at 1 year were significantly lower with the thinner-strut stent among a large cohort of propensity-matched patients. 

Why it Might Matter

Fewer thin-strut devices hold US Food and Drug Administration approval in the United States—coincidentally, the latest entry, Xience Sierra (Abbott), was cleared by the FDA yesterday—and because most hospitals negotiate purchasing agreements with a limited number of suppliers, most physicians don’t have a wide range of devices to choose from outside of academic studies.

Asked about the rationale for conducting SORT-OUT VIII given the constraints on choice, Maeng pointed out that the SORT-OUT series of trials have been designed with the aim of checking the safety and efficacy of market-approved devices in “real-world” patients over the long term.

“It is very important that we continue to evaluate the stents on the market because they are changing all the time,” he told TCTMD. “The BioMatrix is now being changed into a cobalt-chromium device and on the Synergy stent the polymer was changed, from a permanent polymer to an absorbable polymer with 3 months duration before it goes away. So, we have to continue to monitor the outcomes with these stents, and that is the main purpose of the SORT-OUT trials, to monitor new stents coming on the market to make sure they maintain the good results that we are seeing right now with drug-eluting stents.”

Also commenting on the trial for TCTMD, David Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), pointed out that the regulator pathway in Europe is much less rigorous than that in the United States, with no postmarketing requirement. As such, he said, “these studies do provide some insight into commonly used products that the medical community otherwise does not have a structure for studying. It seems boring in hindsight when the results are 'noninferior' but if a safety risk, for example, were identified with a product, it might not otherwise be identified. In an extreme example, think if BVS were approved as it was with CE Mark and with no dedicated postmarket study, its limitations would not come to the forefront without investigator-initiated studies.”