While the disappearing drug-eluting stent seems to have faded from view for the time being, several manufacturers have invested in fabrication of drug-eluting stents with polymers that absorb once the drug of elution has done its work. A new study indicates that patients who have already had a myocardial infarction fare better on stents made with these biodegradable polymers, an outcome that may soon push second-generation DES devices into med-tech history.
The study of more than 13,000 patients diagnosed with acute myocardial infarct, which appears in JACC; Cardiovascular Interventions, relied on a registry for patients in South Korea, all of whom underwent percutaneous coronary intervention (PCI) between November 2011 and December 2015. The study matched three biodegradable-polymer DES (BP-DES) units eluting biolimus (two of the three stents) and sirolimus with four durable-polymer DES (DP-DES) units, two each of which elute everolimus and zotarolimus. Roughly 5,500 of the treated patients were diagnosed with ST-segment elevated infarction (STEMI), while slightly fewer than 5,000 were non-STEMI cases.
Roughly 2,260 patients were randomized to the BP-DES arm, with the majority of these treated with the Biomatrix Flex stent by Biosensors Inc., of Newport Beach, Calif. The DP-DES arm of the study accounted for nearly 8,200 enrollees, the majority of which were treated with stents made by Boston Scientific Corp., of Marlborough, Mass., or Abbott Vascular of Santa Clara, Calif. Everolimus was the predominant antiproliferative used in the stents in the DP-DES arm of the study.
Thickest struts seen in biodegradable units
The analysis required a series of nearly 1,700 matched pairs from each arm, but there were significant differences in stent strut thickness and in stent material composition between the tested devices. The thickest struts were seen in the Biomatrix Flex and the Nobori stents, each at 120 micrometers (µm), both of which fell into the BP-DES group and eluted biolimus. The sirolimus-eluting Orsiro stent by Biotronik SE & Co., of Berlin was the thinnest at 60µm, while all the devices in the durable-polymer group came in at either 81µm or 91µm. The Orsiro was the only BP-DES unit that relied on a non-stainless-steel stent frame, using instead cobalt-chromium (CC), while the second-generation durable polymer devices relied on a variety of alloys, including CC, platinum-chromium, and cobalt-nickel.
The rate of major cardiac adverse events (all-cause death, recurrent infarct or any revascularization) was seen in 14.3% of the BP-DES patients at a median follow-up of 723 days for the entire study population, significantly lower than the rate in the DP-DES group as demonstrated by the hazard ratio of 0.845. That hazard ratio fell to 0.669 after propensity matching. The all-cause death component suggested a similar hazard ratio favoring the BP-DES devices (0.831), another measure that more heavily favored the BP-DES group after propensity matching (0.752). Rehospitalization again favored the BP-DES group, although the difference between the entire cohort and the propensity-matched cohort was narrower than in the primary outcome measures.
One of the more interesting outcomes from this study, however, was that the differences in revascularization, stroke and definite/probable stent thrombosis did not significantly vary in either the entire cohort or in the propensity-match analysis. Prior infarct was significantly higher in the cohort as a whole (4.2% BP-DES vs. 6.3% for DP-DES) for the legacy devices, although the difference narrowed to statistical insignificance in the propensity-matched analysis. Diabetes mellitus was another difference that failed to reach statistical significance in the propensity-matched group despite reaching a significant p score in the cohort as a whole.
Class effect a dangerous assumption
In an accompanying editorial, three cardiologists from Bern University Hospital in Bern, Switzerland, said the outcome of this study corroborates earlier findings from other randomized, controlled trials as well as large-scale observational data sets. However, the Swiss cardiologists noted that the design of the study presumes a class effect between polymer types despite that strut design, material and thickness also play a role in outcomes. Other factors cited include polymer thickness and coating distribution, as well as rate/timing of elution. They noted that the difference in strut thicknesses seen in the BP-DES group calls into question the notion that the three devices can be analyzed as a group.
The authors also questioned whether a roughly two-year follow-up suffices to evaluate the effect of polymer on adverse events, and argued that the clinical endpoints in this study were more patient-directed than device-oriented. The absence of measures for target-vessel infarct and target-lesion revascularization would have lent more credibility to the device-versus-device analysis, and thus the selection of endpoint provides less clarity as to whether patient-specific factors played a primary role in outcomes.
There are other studies that lend credence to the notion that a BP-DES device improves outcomes compared to durable-polymer devices, including the BIOSTEMI study, but the authors of the editorial also remarked that reduced stent strut thickness can improve outcomes, assuming radial force is not compromised. Despite the lack of utter clarity seen in this latest study, the authors said, the combination of biodegradable polymers and ultra-thin stent struts “achieve the best stent-related outcomes in (PCI) patient with STEMI.”