Safety and Efficacy of Ultra-Thin , Biodegradable Polymer Coated Sirolimus-Eluting Supralimus-Core Stents in Real-World Patients : Outcomes at 24-Month Follow-Up

Aim: The purpose of this registry was to establish long-term safety and efficacy through implantation of Supralimus-Core sirolimus-eluting stents (SES) in real-world patients with coronary artery disease (CAD). Methods: The present registry was a retrospective, singe-arm, single-centre, investigator-initiated registry. A total of 372 consecutive patients were implanted with Supralimus-Core SES between January 2015 and November 2016. The primary endpoints were major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR) at 24 months. The secondary endpoints were all-cause death and all separate components of the primary endpoint. Additional endpoints included events of stent thrombosis classified as definite, probable, and possible stent thrombosis. Follow-ups were conducted at 30-days, 6-months, 12-months and 24-months after the index procedure. Results: The mean age of the registry population was 56.3 ± 11.1 years. Males constituted 276 (74.2%) patients. Hypertensives, diabetics, alcoholics, tobacco chewers and smokers comprised 198 (53.2%), 160 (43.0%), 93 (25.0%), 91 (24.5%) and 88 (23.7%) of the registry population, respectively. The mean length and diameter of stents implanted was 19.3 ± 8.8 mm and 2.9 ± 0.3 mm, respectively. At the 24-month follow-up, MACE was reported in 14 (3.8%) patients. Cardiac death, MI, TLR and TVR was reported in 7 (1.9%), 4 (1.1%), 3 (0.8%) and 4 (1.1%) patients, respectively. Overall stent thrombosis occurred in 4 (1.1%) patients. Conclusions: The low MACE rate of 3.8% at the 24-month follow-up indicates favorable long-term results after implantation of the ultra-thin strut Supralimus-Core SES in all-comer, How to cite this paper: Jain, K.J.K., Dasarapu, S., Oruganti, S.S., Maddury, J., Bhyravavajhala, S., Nuthalapati, R.K., Lakshmi, K.S.B., Betham, R. and Enikapalli, A.K. (2018) Safety and Efficacy of Ultra-Thin, Biodegradable Polymer Coated Sirolimus-Eluting Supralimus-Core Stents in Real-World Patients: Outcomes at 24-Month Follow-Up. World Journal of Cardiovascular Diseases, 8, 523-532. https://doi.org/10.4236/wjcd.2018.811051 Received: November 2, 2018 Accepted: November 27, 2018 Published: November 30, 2018 Copyright © 2018 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access K. J. K. Jain et al. DOI: 10.4236/wjcd.2018.811051 524 World Journal of Cardiovascular Diseases real-world patients.


Introduction
Percutaneous coronary intervention (PCI) has emerged as the standard treatment for coronary artery disease (CAD) [1].Naturally, stent design has rapidly evolved over the past decades.Bare-metal stents (BMS) were the first stents licensed for use in cardiac arteries [2].These BMS caused neointimal hyperplasia consequential of proliferation and migration of smooth muscle cells and extracellular matrix production [3].The resultant restenosis rates led to the downfall of BMS and inception of the drug-eluting stent (DES) era.The first generation DES incorporated release of an antiproliferative drug from a permanent polymer coated on a BMS platform.The drug sirolimus displayed efficacy in preventing hyperplasia due to vascular injury after stent implantation.Hence, it is being considered as an agent for prevention of restenosis [4].Although these stents achieved reduced restenosis and revascularization rates, presence of the permanent polymer is linked to delayed healing, inflammatory reactions, hypersensitive reactions, and late and very late thrombosis [3].To resolve this issue, second generation stents were introduced.These stents have the advantage of a biodegradable polymer.The polymer degrades after drug elution to avoid unfavourable effects due to their permanent existence [3].Polymer degradation reduces local inflammatory reaction and irritation, leaving behind only a metal stent adhered to the artery wall [2].Despite this benefit, concerns regarding long-term safety and efficacy are still prevalent.Supralimus-Core sirolimus-eluting stent (SES) (Sahajanand Medical Technologies Pvt. Ltd., Surat, India) utilizes a 60 μm ultra-thin, L605 cobalt-chromium stent platform coated with a biodegradable polymer for delivery of sirolimus drug.This ultra-thin platform provides flexibility for easy deliverability [3].The serpentine strut design permits uniform stress distribution at expansion whereas alternate links permit vessel trackability [2].The present registry aimed to establish long-term safety and efficacy through implantation with Supralimus-Core SES in a "real-world" population.

Study design and patient population
This was a retrospective, singe-arm, single-centre, investigator-initiated registry conducted at a tertiary-care centre in India.Patients, diagnosed with CAD and underwent PCI with at least one Supralimus-Core SES between January World Journal of Cardiovascular Diseases 2015 and August 2016, were included in the registry.The registry was aimed at studying a "real-world" population; hence, no major clinical or angiographic exclusion criteria were defined.All patients provided informed consent for the procedure, and subsequent data collection and analysis for the research purpose.

Description of study stent
The Supralimus-Core SES has a 60 μm thin stent platform made of L605 cobalt-chromium alloy.This platform is coated with a combination of biodegradable polymers and 1.4 μg/mm 2 sirolimus drug.This coating is conformal around the stent struts and is not limited to the abluminal surface of the stent.The biodegradable polymer matrix comprises poly L-lactide (PLLA), 50/50 poly DL-lactide-co-glycolide (PLGA) and polyvinyl pyrrolidone (PVP), which control drug release from the stent.Approximately 70% of the drug is released within 7 days whilst the remaining drug is released over an interval of 48 days [4].After drug release, the polymers degrade naturally and are excreted from the body in the form of their metabolites.The average coating thickness of Supralimus-Core ranges from 5 -6 μm.Supralimus-Core was made available in lengths of 8, 12, 16, 20, 24, 28, 32, 36 and 40 mm and diameters of 2.5, 2.75, 3.0 and 3.5 mm during the registry.

Interventional procedure and adjunctive medications
All procedures and medication regimes followed standard hospital procedures.
Other devices were also permitted however, stent implantation with a Supralimus-Core SES was mandatory.Pre-procedure patients were administered a dose of 300 mg clopidogrel orally 24 hours before the procedure.An intra-arterial bolus of 100 IU/kg unfractionated heparin was administered to patients to achieve an activated clotting time ≥ 250 sec and to initiate the procedure.Administration of glycoprotein IIb/IIIa inhibitors IIb/IIIa inhibitor was left to the investigator's discretion.Post-procedural antiplatelet regimen included indefinite aspirin therapy (75 mg/day) along with clopidogrel orally for at least 6 after the procedure.

Data collection and patient follow-up
Demographic data such as age, gender, cardiovascular risk factors and cardiovascular history were extracted from patient hospital records.Details of affected lesions and stent implantation were collected from angiography and angioplasty reports.Adverse events, angina status, and cardiovascular medication intake were assessed during hospital stay.Patients were followed up at 30-day, 6-months, 12-months and 24-months.The follow-up data were collected retrospectively from existing databases where index and follow-up data existed or was obtained by telephonic contact.

Study endpoints
The primary endpoint of the registry was major adverse cardiac event (MACE).MACE was defined as a composite of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and non-target lesion target vessel revascularization (non-TL TVR).The secondary endpoints included all-cause death and all separate components of the primary endpoint.Additional end-World Journal of Cardiovascular Diseases points included events of stent thrombosis classified as definite, probable, and possible stent thrombosis based on the criteria defined by the Academic Research Consortium (ARC) [5].
Death due to undetermined cause was defined as cardiac death unless a non-cardiac cause was established through clinical and/or pathological study.MI was defined as either development of new pathological Q waves in at least two contiguous leads of the electrocardiogram with or without elevated cardiac enzymes or elevation of creatine kinase greater than three times the upper limit of normal and without pathological Q waves in the electrocardiogram.TLR was considered when there was stenosis in the treated segment (5 mm proximal and 5 mm distal edges).TVR was defined as repeat revascularization of the same vessel treated in the index procedure.Stent thrombosis was defined as: "definite" when detected angiographically; "probable" if the patient had a target vessel-related MI or died of a coronary event within the first 30 days; and "possible" if any unexplained death occurred from 30 days after the index procedure until the final follow-up.

Discussion
The purpose of the current registry was to evaluate long-term safety and efficacy of the Supralimus-Core SES in real-world patients.The low MACE rates observed at 12 (3.0%)and 24 months (3.8%) demonstrate favorable results.
MACE rates are favourable with the Supralimus-Core SES even at the 24-month follow-up.The SPIRIT III [14] trial reported MACE in 49 (7.7%) and 42 (13.8%)patients in everolimus-eluting stent (EES) and paclitaxel-eluting stent (PES) groups, respectively [14].Similarly, Erdim et al. [15] reported two-year MACE in 4 (8.3%) and 13 (16.4%)patients in SES and PES groups, respectively [15].The SIRIUS trial [16] examined two-year clinical outcomes in patients with de novo native coronary lesions.The study reported MACE in 55 (10.3%) and 132 (25.1%) patients in SES and control stent groups, respectively [16].The present registry reported MACE in 14 (3.8%) patients at the 24-month follow-up.These previous studies indicate lower rates of MACE achieved with SES as compared to other control stents.These studies also highlight the even lower MACE rate Supralimus-Core has achieved compared to earlier studies of SES.
Statistical analysis Continuous variables are represented as means with standard deviations and categorical variables as counts and percentages.All data were processed using the Statistical Package for Social Sciences (SPSS, Chicago, IL, USA) program version 15.The Kaplan-Meier graph was used to summarize cumulative MACE at 24 months.
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[10]anent polymers were the pitfall of first generation SES.These permanent polymers were associated with inflammation at the vessel site and delayed healing.These occurrences partially justify increased incidences of late stent thrombosis, very late stent thrombosis and long-term adverse effects[5].This has in turn brought about the advent of biodegradable polymers.Degradation of the polymer reduces risks of stent thrombosis experienced with first generation stents as evidenced by several trials[8][9][10].