No Harm, No Help With Bioabsorbable-Polymer Stents: Registry

(UPDATED) There is no difference in in-hospital outcomes or longer-term mortality between patients undergoing revascularization with either a durable-polymer DES or newer technology with a bioabsorbable polymer, according to the results of a retrospective analysis.

Among more than 53,000 consecutive PCIs performed between 2015 and 2018 in Michigan, researchers found there was no difference in the risk of in-hospital mortality or stent thrombosis between patients who received the bioabsorbable-polymer everolimus-eluting stent (Synergy; Boston Scientific) and those treated with either the durable-polymer everolimus-eluting stent (Xience; Abbott Vascular) or the durable-polymer zotarolimus-eluting stent (Resolute; Medtronic).

Importantly, at 2 years, there was also no significant difference in the risk of death between the stent groups.

“Ultimately, one of the reasons we performed this analysis was because there is some data suggesting that perhaps use of the Synergy stent is associated with a higher risk of stent thrombosis,” lead investigator Nadia Sutton, MD (University of Michigan Cardiovascular Center, Ann Arbor), told TCTMD. “We use multiple different stent types and different stent types are used around the state of Michigan, so we were interested in looking at our database to see if there was any signal towards increased harm.”

In 2017, for example, researchers published data from the US Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database hinting at an increased risk of acute stent thrombosis with the bioabsorbable-polymer Synergy stent. That was followed by a report from the Bern PCI Registry that suggested a higher risk of acute stent thrombosis among high-risk patients who received Synergy, although there was no difference in stent thrombosis or device-oriented clinical events at 1 year. These potential signals were not observed in any of the randomized controlled trials, such as EVOLVE II or BIO-RESORT, however.

For Nigel Jepson, MD (Prince of Wales Hospital, Sydney, Australia), who wasn’t involved in the analysis, the new study confirms what most interventionalists tend to believe, namely that there isn’t an increased risk of acute stent thrombosis with Synergy compared with durable-polymer DES.

“It helps reassure operators and the institutions that default to Synergy, at least in-hospital and at 30 days, that the results are comparable to durable-polymer stents,” he told TCTMD. As for the mortality data, which are based on just 20% of the overall cohort, “it’s really hard to say what’s really happening at 2 years, but there are randomized data which are good for ultrathin, biodegradable-polymer stents and that at least match Xience and the zotarolimus-eluting Resolute Onyx platform at 2, 3, and even 5 years,” continued Jepson. “I see it as an even playing field with the major endpoints, both early and late.”   

Turning to the BMC2

To address any potential differences in safety or efficacy between the stent types, the researchers turned to the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). Published February 25, 2021, in Circulation: Cardiovascular Interventions, the new analysis included 53,724 patients from 48 hospitals who underwent PCI: 59% were treated with Xience, 27% with Resolute, and 14% with Synergy. Those given Synergy stents were more likely to present with NSTEMI but also were more likely to be higher-risk patients undergoing complex procedures. For example, they were more likely to require multivessel revascularization, left main PCI, revascularization for chronic total occlusion, mechanical support, and atherectomy.   

“We did observe unadjusted increased in-hospital complications in patients treated with [Synergy] stents,” said Sutton, “but it had more to do with patient selection and procedural characteristics than it had to do with the stents, based on the adjusted data.”

After propensity-matching, there was no significant difference in the risk of in-hospital mortality, stent thrombosis, or stroke (a falsification endpoint) between patients treated with the Synergy versus Xience stents. Compared with the Resolute stent, there also was no signal of higher in-hospital mortality, stent thrombosis, or stroke among the Synergy-treated patients. Finally, there was no difference in clinical events in a comparison between Xience- and Resolute-treated patients.     

Within the BMC2, the researchers also had access to mortality data from Medicare fee-for-service patients. After adjusting for baseline characteristics and procedural factors, there was no difference in the risk of death at 2 years among the three stent types.

“One of the limitations of our study is that we did not have the ability to look at late stent thrombosis, or very late thrombosis, because our registry doesn’t capture that data,” said Sutton. “However, we figured that the most catastrophic complication of stent thrombosis is death. So by looking at death as a primary outcome, which we did have access to, at least for the Medicare patients, that was a very reassuring finding.” She added that 2 years is the longest duration they could assess because the Synergy stent hasn’t been on the market long enough to have an adequate number of patients with extended follow-up.

If the stents all perform equally, it raises the question of how we justify choosing stents that are more costly. Nadia Sutton

The bioabsorbable-polymer DES, which include Synergy and other stent platforms, are being marketed toward patients in need of shortened dual antiplatelet therapy, said Jepson. Synergy introduced the aspect of “healing,” which was more a marketing than a biological concept, he commented, but there are a number of smaller studies that suggest patients at high bleeding risk do better with shortened dual antiplatelet therapy when treated with bioabsorbable-polymer DES.  

“That’s where we could conceivably be using these [bioabsorbable-polymer] stents in 2021, but I think that with second- and third-generation drug-eluting stents, it’s really hard to pick a winner,” said Jepson. “The data are really showing equipoise.”

He added that the ultrathin Orsiro stent (Biotronik) with bioabsorbable polymer does have good data when compared against Xience, particularly in the BIOFLOW V and BIOSTEMI studies, although those trials can be criticized for patient mismatch in the study arms and their endpoint definitions. The newer bioabsorbable-polymer stents, he added, don’t quite have as much data supporting their use in complex lesion sets, such as chronic total occlusions, left main coronary artery disease, or heavily calcified lesions. However, that’s mainly because they haven’t been around as long, said Jepson.

Ajay Kirtane, MD (NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY), who wasn’t involved in the study, said the distribution of stent use by hospitals participating in the BMC2 is one of the paper’s more interesting aspects, although the variability across centers is “likely as much a result of contracting [as it is] clinical decision-making,” he told TCTMD. While these new data further the ability to make comparisons between stent types, “given the differences in baseline characteristics, it’s hard to be definitive about specific differences between stents,” he said in an email.

Nonetheless, the absolute rates of adverse short-term events are low with Synergy, Resolute, and Xience, and this “speaks to the great strides made in stent development over the years,” said Kirtane.

Costs and Contracts

To TCTMD, Sutton said the theoretical advantage of devices with a bioabsorbable polymer is to dampen inflammation or delayed healing that can result from a durable polymer. Synergy, in particular, has an advantage in that the polymer coating is applied only on the abluminal side of the stent, the idea being it furthers more-rapid endothelialization, which in turn could translate into a lower risk of late stent thrombosis and shorter-duration dual antiplatelet therapy.

Despite the proposed advantages, however, several studies comparing different stent platforms with durable and biodegradable polymers in various patient populations have now challenged the theoretical benefits of these newer devices. At TCT Connect 2020, a Korean study of ACS patients treated with a wide range of durable- and bioabsorbable-polymer stent types found no difference in the risk of patient-oriented clinical outcomes, but did observe lower 1-year rates of cardiac death, target-vessel MI, or TLR with the durable-polymer devices. Like Kirtane, several experts also have noted that any new device will face large hurdles when trying to show superiority over existing technology. 

Sutton said that while their large analysis ended up showing no difference between stent types, the lack of difference is relevant and important for hospitals and interventionalists. The price of stents varies between hospitals, with prices sometimes tied to larger contracts with manufacturers and associated rebates, but their new study questions whether hospitals should be paying more for any specific stent type if there are no clinical differences.

“If the stents all perform equally, it raises the question of how we justify choosing stents that are more costly,” said Sutton. “This is particularly important in this past year, when hospitals are all looking for ways to cut down on costs.”