Clinical rationale and experimental feasibility of the first national drug-eluting stent platform

Background.The availability of drug-eluting stents with evidence-based clinical safety and efficacy produced in the Russian Federation is one of the relevant goals for successful treating of patients with coronary artery disease, including acute coronary syndrome. Aim To confirm clinical rationale and experimental feasibility of the first Russian drugeluting stent, Calypso (Angioline, LLC, Russian Federation), for the clinical practice.

Methods.The study included four phases. The first phase was aimed at selecting the optimal stent platform with superior healing properties. Then, the selected Russian coronary stents based on the optimal platforms underwent preclinical studies. The third phase included the clinical assessment using optical coherence tomography (OCT) in order to confirm the preclinical results. The last phase was focused on assessing clinical safety and efficacy of the Russian coronary stent based on the comparative analysis of angiographic findings within the 12-months follow-up.

Results.At the first phase, biodegradable polymer sirolimus-eluting stent showed superior healing properties in comparison with the healing score of 18±14.97 for Orsiro stents (Biotronik, Germany) versus 25.6±1.0 for Xience stents (Abbott Vascular, USA) versus 32.5±20.3 for Synergy (Boston Scientific, USA), p<0.001. The Russian stent consistently demonstrated a high healing profile in preclinical and OCT clinical studies. The results of the comparative clinical study proved the clinical safety and efficacy of the Russian stent that was similar to the best foreign stents. None of the differences in the incidence of binary restenosis were found between the groups (p<0.05).

Conclusion.The biodegradable polymer sirolimus-eluting stent Calypso manufactured in the Russian Federation demonstrated superior neointimal healing pattern with no signs of chronic inflammation in the experiment. This stent reported high neointimal healing properties according to the clinical OCT study. According to the angiographic findings, the incidence of binary restenosis between the Russian biodegradable polymer sirolimus-eluting stent and durable polymer everolimuseluting stents was similar at the 12-months follow-up (p>0.05).

1. Alekyan B.G., Grigor'yan A.M., Staferov A.V., Karapetyan N.G. Endovascular diagnostics and treatment in the russian federation (2017). Russian journal of Endovascular surgery. 2018; 5(2): 93-240. (In Russian)

2. Byrne R. A., Joner M., Kastrati A. Polymer coatings and delayed arterial healing following drug-eluting stent implantation. Minerva cardioangiologica. 2009; 57(5): 567-584.

3. Cook S., Wenaweser P., Togni M., Billinger M., Morger C., Seiler C., Vogel R., Hess O., Meier B., Windecker S. Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation. Circulation. 2007; 115 (18): 2426-2434. doi: 10.1161/CIRCULATIONAHA.106.658237

4. Iakovou I., Schmidt T., Bonizzoni E., Ge L., Sangiorgi G.M., et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. Jama. 2005; 293(17): 2126-2130.

5. Joner M., Finn A.V., Farb A., Mont E.K., Kolodgie F.D., Ladich E., Kutys R., Skorija K., Gold H.K., Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. Journal of the American College of Cardiology. 2006; 48 (1): 193-202. doi: 10.1016/j. jacc.2006.03.042

6. Daemen J., Wenaweser P., Tsuchida K., Abrecht L., Vaina S., Morger C., et al. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. The Lancet. 2007; 369 ( 9562): 667-678. doi: 10.1016/ S0140-6736(07)60314-6

7. Moreno R., Fernández C., Hernández R., Alfonso F., Angiolillo D.J., Sabaté M. et al. Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies. Journal of the American College of Cardiology. 2005; 45 (6): 954-959. DOI: 10.1016/j.jacc.2004.11.065

8. Nebeker J. R., Virmani R., Bennett C.L., Hoffman J.M., Samore M.H., Alvarez J. et al. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. Journal of the American College of Cardiology. 2006. 47 (1): 175-181. doi: 10.1016/j. jacc.2005.07.071

9. Prokhorikhin A.A., Verin V.V., Osiev A.G., Ganyukov V.I., Protopopov A.V., Dyomin V.V., Abugov S.A., Baystrukov V.I., Grazhdankin I.O., Ponomaryov D.N., Kretov E.I. Prospective rAndomized, single-blind, mulTicenter control clinical study of sirolimus-eluting coRonary stent “Calypso” vs everolimus-elutIng cOronary sTent “Xience Prime”: design and rationale for “PATRIOT” trial. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2016; 20(4): 96-101. doi: 10.21688/16813472-2016-4-96-101 (in Russian)

10. Prokhorikhin A.A., Baystrukov V.I., Grazhdankin I.O., Ponomarev D.N., Verin V.V., Osiev A.G., Ganyukov V.I., Protopopov A.V., Dyomin V.V., Abugov S.A., Boykov A.A., Malaev D.U., Karaskov A.M., Pokushalov E.A., Kretov E.I. Prospective randomized, single-blind, mulTicenter study of sirolimus-eluting coronary stent “Calypso” vs everolimuseluting coronary stent “XiencePrime”: results of the PATRIOT trial. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2017;21(3):76-85. doi: 10.21688/1681-3472-2017-3-76-85 (In Russian)

11. Vorobev V.L., Semenihin A.A., Grachev N.I., Verin V.V. Clinical outcomes of one-year prospective study on application of Calypso coronary stents in patients with acute coronary syndrome. Patologiya krovoobrashcheniya i kardiokhirurgiya. 21(1): 44-49. doi: 10.21688/1681-3472-2017-1-44-49 (In Russian)

12. Lopotovskiy P.Y., Parkhomenko M.V., Kokov L.S. Preliminary results of a retrospective study register for the use of Russian stents "Sinus" and "Calypso". Vestnik Roszdravnadzora. 2015; 5: 44-49. (In Russian)