Drug-eluting stents with biodegradable polymers have theoretical advantages over drug-eluting stents with permanent polymers—even second-generation drug-eluting stents—because they may be able to resolve the issue of late catch-up. While these advantages have not been observed with first-generation biodegradable polymer stents, they may yet be seen with the newer generation of biodegradable polymers stents.
Second-generation drug-eluting stents reduce the risk of stent thrombosis compared with first-generation devices. However, these advantages may decrease over time. Jose de la Torre Hernandez (Interventional Cardiology Department, Hospital University Marques de Valdecilla, Santander, Spain), speaking at the Intravascular Imaging in Complex PCI meeting, commented that, according to the results of the SPIRIT III study,1 percutaneous coronary intervention (PCI) with everolimus-eluting stents are associated with significant reductions in target lesion failure at five years compared with PCI with paclitaxel-eluting stents. However, he added there was a “continuous accrual of events” with everolimus-eluting stents: the rate of target lesion failure with these stents was 5.4% at one year vs. 12.7% at five years. Furthermore, two-year data from the study indicate that in-state lumen loss increases over time with everolimus-eluting stents. “The phenomenon of late catch-up [with second-generation drug-eluting stents] atherosclerosis is a real problem,” de la Torre Hernandez stated.
This issue of late catch-up may be related to the permanent polymer. In an autopsy review of patients who received a first-generation drug-eluting stent, Finn et al report that the “most powerful predictor” of stent thrombosis was endothelial coverage and the “best morphometric predictor of late stent thrombosis was the ratio of uncovered to total stent struts”.2 They add: “Although the mechanisms by which the current-generation drug-eluting stents induce non-union incomplete healing are not fully understood, lesion characteristics, drug properties, dose, and distribution, and polymer biocompatibility play important roles.” Furthermore, Finn et al note that the non-absorbable polymers of the first-generation stents provoke “chronic eosinophilic infiltration of the arterial wall” in a small of patients “suggesting hypersensitivity reactions in a small number of cases”. “To what extent polymer-induced inflammation also plays a role in retarding healing is unknown, but in some cases, it clearly is casual in inducing thrombosis”, they add.
Therefore, a stent with biodegradable polymer has theoretical advantages compared with a permanent polymer stent. However, data for the first generation of biodegradable polymer stents have been mixed. A meta-analysis indicated that Yukon Choice (Translumina) and BioMatrix Flex (Biosensors)—both of which have biodegradable polymers—had superior safety and efficacy outcomes at four years compared with the first-generation drug-eluting stent Cypher Select (Cordis).3
However, de la Torre Hernandez said that these data may no longer be relevant for clinical practice, commenting “We are not using Cypher; we are not using Taxus. We are using second-generation drug-eluting stents.” He added that a large-scale network meta-analysis4 found that stents with a biodegradable polymer had similar rates of cardiac death/myocardial infarction and target vessel revascularisation compared with second-generation drug-eluting stents but had higher rates of stent thrombosis than everolimus-eluting stents with a cobalt-chromium platform.
In a different meta-analysis, Bangalore et al5 found that biodegradable polymers were not superior to second-generation drug-eluting stents and concluded: “Newer generation durable polymer stents, and especially cobalt chromium everolimus-eluting stents, have the best combination of safety and efficacy. The utility of biodegradable polymer stents in the context of excellent clinical outcomes with newer generation durable polymer stents need to be proven.”
According to de la Torre Hernandez, the concept of biodegradable polymers is “evolving”. He explained that with newer generations of biodegradable polymer stents, both the release of the drug and the absorption of the polymer are quicker. For example, with Boston Scientific’s Synergy stent, the drug is released within three months and the polymer is absorbed within four months. However, with the BioMatrix stent, the drug is released over six months and the polymer is absorbed within nine months—de la Torre Hernandez commented that: “the polymer is still there at 12 months” in some studies”. He added that second-generation biodegradable polymers also have thinner polymers compared with earlier generations (eg. Synergy has a strut thickness of 74µg vs. 120µg for BioMatrix).
De la Torre Hernandez reported that the data for these second-generation biodegradable polymer stents are encouraging, noting: “They have equal or less stent thrombosis than Xience [a second-generation, everolimus-eluting stent that is considered to be the gold standard].” He added that a “promising signal” from the EVOLVE II study,6 which compared the Synergy stent to Promus Element Plus (an everolimus-eluting stent from Boston Scientific), was that no cases of stent thrombosis were observed with the biodegradable polymer stent after six days. The study also found that, overall, Synergy was non-inferior to Promus Element Plus, in terms of the rate of primary endpoint of target lesion failure at 12 months.
Second-generation biodegradable polymer stents, de la Torre Hernandez explained, could potentially reduce the rate of late stent thrombosis compared with second-generation permanent polymer stents but “three or four-year follow-up data” for these devices are needed to show this. He added that if biodegradable polymer stents were found to reduce to risk of late stent thrombosis, this could have implications for optimal duration of dual antiplatelet therapy (DAPT)—ie. shorter DAPT periods could be prescribed. “There is no class-effect for drug-eluting stents in this regard and stents-specific studies are required. But for clinical trials to have enough power to compare DAPT periods, they need to have very large patient cohorts.” he stated. Before such trials can be conducted, de la Torre Hernandez added, early healing (as a surrogate marker of the risk of stent thrombosis) studies with optical coherence tomography (OCT) are warranted. Thus, if such studies do not show better early healing (or show worse healing) with the Synergy, shorter DAPT studies should not be performed.
De la Torre Hernandez commented that the ongoing ESTROFA OCT multi DES study is comparing OCT evaluation (at six months and 12 months) of patients treated with biodegradable polymer stents with that of patients treated with the bioresorbable vascular scaffold (Absorb, Abbott Vascular). All patients in the study have ≥2 lesions that have comparable characteristics and are being treated with non-overlapping stents. The aim is to enrol 100–125 patients (at present, 91 patients have been enrolled).
A case report, by de la Torre Hernandez and colleagues,7 has already indicated that Synergy may be associated with better early healing than Absorb. In this report, a 43-year-old man with lesions in his left anterior descending artery received the Synergy stent in his most distal lesion and Absorb scaffolds in his mid and proximal lesions (the original treatment plan was for him to receive Absorb in all lesions). OCT imaging data at two months showed “complete and smooth coverage” over all struts of the Synergy stent whereas the degree of strut coverage bioresorbable vascular scaffolds was “high but not complete”. De la Torre Hernandez et al note that this difference in strut coverage “could be related mostly to the large different in strut thickness (74µm for Synergy vs. 150µm for Absorb)”. According to de la Torre Hernandez, the six-month OCT data are very different for Synergy than for Absorb.
“The new generation of biodegradable-polymer drug-eluting stents are much thinner and have quicker polymer absorption, which may provide an advantage in terms of early healing,” de la Torre Hernandez concluded. He noted that this could lead to greater safety with shortened, interrupted or discontinued DAPT.
References
- Gada et al. JACC Cardiovasc Interv 2013; 6(12): 1263–66.
- Finn et al. Circulation 2007; 115; 2435–41.
- Stefanini et al. European Heart Journal 2012; 33: 1214–22.
- Palmerini et al. JACC 2014: 63: 299–307.
- Bangalore et al. BMJ 2013; 347: Epub.
- Kereiakes et al. Cir Cardiovasc Interv 2015; Epub.
- de la Torre Hernandez et al. EuroIntervention 2015; Epup
This article was published in the supplement Current issues in PCI: The latest data (download here). The supplement reported on The Intravascular Imaging in Complex PCI meeting, which was supported by an unrestricted educational grant from Boston Scientific, AstraZeneca, and Infraredx. Boston Scientific also provided an educational grant for the production of the supplement but had no input into the final editorial content.
