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ORIGINAL ARTICLE
Year : 2016  |  Volume : 4  |  Issue : 1  |  Page : 5-9

Clinical performance of biodegradable polymer coated Sirolimus-eluting stent in multivessel disease: Results from MULTIDES study


1 Department of Cardiology, Heart and Brain Centre, Lalitha Super Speciality Hospital Pvt. Ltd., Guntur, Andhra Pradesh, India
2 Department of Cardiology, Apollo Hospitals, Ahmedabad, Gujarat, India
3 Department of Cardiology, Yashfeen Cardiac Hospital, Navsari, Gujarat, India
4 Department of Clinical Trials, Sahajanand Medical Technologies Pvt. Ltd., Surat, Gujarat, India

Date of Web Publication4-Mar-2016

Correspondence Address:
Ashok Thakkar
Department of Clinical Trials, Sahajanand Medical Technologies Pvt. Ltd., Surat - 395 004, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2321-449X.178118

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  Abstract 

Context: The role of percutaneous coronary intervention in the treatment of multivessel coronary artery disease (CAD) is still controversial and widely discussed. Aim: The aim of this study was to examine the incidence of clinical outcomes after utilization of Indolimus, biodegradable polymer coated sirolimus-eluting stent (SES), in multivessel coronary stenting in an unselected patient population. Settings and Design: From April-2012 to June-2014, patients with multivessel (≥2 vessels) disease were examined in the retrospective, nonrandomized, observational, multicenter MULTIDES study. Materials and Methods: A total of 151 patients, exclusively treated with Indolimus SES in multivessel, were included in the study. The study was conducted in accordance with the Declaration of Helsinki and country-specific regulatory requirements. All patients signed informed consent form. Statistical Analysis Used: Continuous variables are presented as mean ± standard deviation and categorical variables as counts and percentages. All data were analyzed using Statistical Package for Social Sciences program. Results: The mean age was 53.7 ± 10.7 years; male gender represented 108 (71.5%) patients. A total of 314 Indolimus stents were implanted. Clinical follow-up was performed at 30-day, at 6-month, and at 9-month. The primary endpoint, major adverse cardiac events (MACEs) at 9-month follow-up, occurred in 5 (3.3%) patients, consisting of 1 (0.7%) cardiac death, 2 (1.3%) myocardial infarction, 2 (1.3%) target lesion revascularization, 0 (0%) target vessel revascularization, and 0 (0%) stent thrombosis. Conclusion: The present study describes that Indolimus implantation is safe and effective treatment in multivessel CAD, showing low rates of MACEs during 9-month follow-up.

Keywords: Biodegradable polymer, multivessel, sirolimus-eluting stent


How to cite this article:
Polavarapu A, Polavarapu RS, Prajapati J, Raheem A, Mayall T, Thakkar A. Clinical performance of biodegradable polymer coated Sirolimus-eluting stent in multivessel disease: Results from MULTIDES study. Heart India 2016;4:5-9

How to cite this URL:
Polavarapu A, Polavarapu RS, Prajapati J, Raheem A, Mayall T, Thakkar A. Clinical performance of biodegradable polymer coated Sirolimus-eluting stent in multivessel disease: Results from MULTIDES study. Heart India [serial online] 2016 [cited 2020 Jul 10];4:5-9. Available from: http://www.heartindia.net/text.asp?2016/4/1/5/178118


  Introduction Top


Multivessel disease (MVD) in comparison to single vessel disease relates to a worsened prognosis and is evidenced in up to half of the patients referred for urgent angiography.[1],[2] The optimal revascularization treatment for patients with MVD remains a subject of debate.[3] However, with recent advancements in endovascular technology and adjunctive pharmacotherapy, multiple-vessel percutaneous coronary intervention (PCI) is now feasible and is associated with outcomes similar to those of single vessel or staged procedures.[4] We, therefore, conducted this observational, multicenter, nonrandomized study to examine the safety and efficacy of the Indolimus sirolimus-eluting stent (SES) in real-world patients with multiple (≥2) coronary lesions.


  Materials and Methods Top


Study design and patient population

From April-2012 to June-2014, a total of 151 patients, exclusively treated with Indolimus SES in multivessel (≥2 vessels), were examined in the retrospective, nonrandomized, observational, multicenter MULTIDES study. The study was conducted in accordance with the declaration of Helsinki and country-specific regulatory requirements. All patients signed informed consent form which was reviewed and approved by the Institutional Review Board or Independent Ethics Committee.

The inclusion criteria for the study were:

  1. Patients of age 18 years or above.
  2. Patients who had stable or unstable angina or acute recent myocardial infarction (MI) and
  3. Patients who were undergoing coronary intervention with MVD.


The patients were excluded if they refused to give written informed consent or if they had any allergy to aspirin, clopidogrel, ticlopidine, heparin, cobalt-chromium (Co-Cr), sirolimus, or polymers used in a study stent.

Description of the study stent

The Indolimus biodegradable polymer coated sirolimus-eluting coronary stent involves L605 (Co-Cr) alloy as its stent platform. The biodegradable polymer gives it a strut thickness of 60 µm and drug load of 1.4 µg/mm 2. About 70% of drug is released within 7 days, and remaining drug is released over a period of 48 days [Figure 1]. The drug is released within 7 weeks after the stent implantation from the polymeric layers coated onto the surface of the stent. The biodegradable polymeric film is a blend of different biodegradable polymers-Poly L-Lactide, 50/50 Poly DL Lactide-co-Glycolide, and Polyvinylpyrrolidone, which undergoes hydrolysis. This process takes approximately 9-12 months after which all the polymer degrades naturally and excretes from the body in the form of their metabolites.
Figure 1: In vitro drug release from Indolimus stent

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The average coating thickness of Indolimus stent is between 5 and 6 µm. The Indolimus stent is available in various lengths and diameters.

Interventional procedure and adjunctive medication

All patients received a loading dose of 300 mg of aspirin and clopidogrel (300 mg) or prasugrel (60 mg) or ticagrelor (two tablets of 90 mg each). The procedural anticoagulation was brought about either with heparin or bivalirudin. However, the intraprocedural administration of glycoprotein IIb/IIIa-inhibitor was at the investigator's volition. The procedure was performed according to the standard treatment guidelines of each participating center. All the patients received dual antiplatelet therapy (aspirin 75-300 mg/day indefinitely and clopidogrel 75 mg/day or prasugrel 10 mg/day or ticagrelor 90 mg twice daily for at least 6 months) after the procedure.

Endpoints of the study

The primary endpoint of the study was major adverse cardiac events (MACEs), which is a conglomerate of cardiac death, MI (Q-wave and non-Q-wave) and target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis (ST). These endpoints were observed during in-hospital stay, at 30-day, 6-month, and 9-month follow-up. MACE will be evaluated as secondary endpoints at 12 and 24 months.

Definition of endpoints and clinical events

Procedural success was defined in terms of in-hospital MACE. MACE is composed of cardiac death, MI, TLR, and TVR. Death can be cardiac or noncardiac death. Any death due to undetermined cause was reported as cardiac death. Q-wave MI was considered when there was development of new Q-wave of more than 0.04 s in two or more adjoining leads along with an increase in cardiac markers such as Troponin I or T, creatine kinase, or MB isoform. Non-Q-wave MI was considered when there was more than 3 times elevation in creatine kinase levels along with elevation in MB isoform and Troponin markers T or I without development of new Q-waves.[5] TLR was considered when there was stenosis in treated segment (5 mm proximal and 5 mm distal edges). TVR was considered when there was stenosis in any segment of the treated vessel. ST was considered acute when it occurred within 24 h, subacute when it occurred between 1 and 30 days, and late when it occurred after 30 days.[5] “Definite” ST was defined by symptoms suggestive of an acute coronary syndrome and angiographic or pathologic confirmation of ST. “Probable” ST was described as unexplained death within 30 days or target vessel MI without angiographic confirmation of ST. “Possible” ST was defined as any unexplained death after 30 days.[6]

Follow-up

All patients were subjected to in-hospital, 30-day, 6-month, and 9-month follow-up. Clinical follow-up was scheduled by telephone communication or clinic visit at 30-day, 6-month, and 9-month. Follow-up data were collected relating to the clinical status, any hospitalization and occurrence of any adverse events. Further follow-up is scheduled to be taken at 12-month and at 24-month.

Statistical analysis

Continuous variables are presented as mean ± standard deviation and categorical variables as counts and percentages. The event-free survival curve was calculated according to the Kaplan-Meier method [Figure 2]. All data were analyzed using the Statistical Package for Social Sciences (IBM SPSS Statistics; Chicago, IL, USA) program, version 15.
Figure 2: Cumulative event-free survival curve at 9-month follow-up

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  Results Top


Baseline demographics and lesion characteristics

A total of 151 patients were enrolled in the study. The basic demographic details of the patients are outlined in [Table 1]. The mean age was 53.7 ± 10.7 years; male gender represented 108 (71.5%) patients; there were 58 (38.4%) and 56 (37.1%) patients of diabetes and hypertension, respectively. The most prevalent clinical presentation was unstable angina in 44 (29.1%) patients, followed by stable angina in 18 (11.9%) patients. Type B2 and C lesions accounted for 82 (27.2%) and 163 (54.0%), respectively. Patients with two and three diseased vessels were 137 (90.7%) and 14 (9.3%), respectively. A total of 314 Indolimus stents (two, three, and four stents in 92.7%, 6.6%, and 0.7% of patients, respectively) were implanted at index procedure (2.1 stents/patients) with an average diameter and total stent length of 3.1 ± 0.4 mm and 26.8 ± 9.2 mm, respectively. The lesion and angiographic procedural details are outlined in [Table 2].
Table 1: Baseline demographic characteristics

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Table 2: Lesion and procedural characteristics

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Clinical outcomes

The primary endpoint, MACE at 9-month follow-up, occurred in five (3.3%) patients, consisting of 1 (0.7%) cardiac death, 2 (1.3%) MI, 2 (1.3%) TLR, 0 (0%) TVR, and 0 (0%) ST. The detailed clinical outcomes of the study are outlined in [Table 3]. Long-term follow-up of the study would further confirm safety and efficacy.
Table 3: Cumulative clinical outcomes up to 9-month (n = 151)

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  Discussion Top


The optimal strategy for the treatment of patients with multivessel coronary artery disease (CAD) has been a matter of conflict.[3] Before the advent of drug-eluting stent (DES), the preferable and superior treatment for MVD was coronary artery bypass grafting (CABG) as compared to bare metal stents (BMS). This was highlighted in Arterial Revascularization Therapies Study (ARTS) and ERACI II trials [7],[8] and also in other studies. The superiority of CABG was due to lower incidences of revascularizations and MACE. However, when the era of DES commenced, these trials as ARTS II and ERACI III further compared CABG with DES in MVD using the same historical control groups.[9],[10] The results of these trials showed a better performance of DES, even though contemporary candidates treated with DES were at higher clinical and anatomical risk than their surgical counterparts.

Overall, four prospective randomized trials have been published comparing CABG with DES in MVD. The results in terms of death, MI, and stroke were similar (P = 0.56) in these trials.[11] As the years passed, the disparity in the need for repeat revascularization following CABG and PCI, which favored surgery, has decreased.[12] Multivessel DES implantation is likely to be considered on a growing proportion of patients who were traditionally referred for CABG surgery. However, the magnitude of this shift has been difficult to quantify and prognosticate.[13]

There have been incessant attempts to find new approaches for the development of DES techniques and devices, from the antecedent durable polymer-based DES toward the biodegradable polymer-based DES, which led to a decrease in the occurrence of adverse events with time.[14],[15] Earlier studies had been performed using Indolimus as the study stent. In the “All-Comers” study, MACE at 6-month was 3.4%,[16] other studies that involved diabetic, and acute MI patients reported MACE to be 4.1% and 4.2%, respectively.[17],[18] These studies depict the consistent efficacy and safety of Indolimus regardless of patient characteristics and complexities. In this study, patient population had higher rates of hypertension (37.1%) and diabetes (38.4%), 26.5% were smokers, and unstable angina (29.1%). The combination of these factors along with an average of 2.1 stents per patient makes the study population atypically complex. In spite of such complications, cumulative MACE at 9-month follow-up was found to be only 3.3% which consisted of one case of cardiac death, two cases of MI, and two cases of TLR.

There have been many recent studies that reflect the preferability of DES in complex anatomical conditions. In a real-world cohort study,[19] comparison of the results of following approaches were performed: BMS only, DES and BMS in the same patient (hybrid stenting), and DES only. The cumulative MACE at 1-year follow-up was 19.3%, 17.9%, and 16.4% for BMS, mixed, and DES, respectively. Whereas the SEEDS study which demonstrated the clinical outcomes of XIENCE V in complex MVD came up with 0.27% cardiac deaths, 4.11% MI, 0.27% TLR, 0.27% acute ST, and 0.40% subacute ST at 30-day follow-up.[20]

Previous studies state that multivessel SES implantation can be safely performed on patients with complex CAD,[21] and it was also identified that independent predictors for consequent cardiac events or repeat revascularization following stent interventions; unstable angina, prior angioplasty or CABG, diabetes mellitus, and reference vessel diameter were associated with clinical events in a multivariate model. Interestingly, the number of vessels treated or stents used did not associate with adverse cardiac end points.[22] Thus, despite of more complex profile and clinical risk factors in this study, there were fewer incidences of MACE which prove the safety and efficacy of Indolimus SES in patients with multivessel, complex CAD.

Study limitations

The study suffers a limitation of its retrospective nature, which resulted in incomplete availability of data regarding many variables.


  Conclusion Top


The present study portrays that Indolimus SES implantation is safe and effective treatment in multivessel coronary artery disease, showing low rates of major adverse cardiac events during 9-month follow-up. Long-term follow-up would further justify the clinical safety and efficacy of Indolimus SES in multivessel disease.

Financial support and sponsorship

Nil.

Conflicts of interest

Tamanpreet Mayall and Ashok Thakkar are employees of Sahajanand Medical Technologies Pvt. Ltd. Other authors do not have any conflicts of interest.

 
  References Top

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Varani E, Balducelli M, Aquilina M, Vecchi G, Hussien MN, Frassineti V, et al. Single or multivessel percutaneous coronary intervention in ST-elevation myocardial infarction patients. Catheter Cardiovasc Interv 2008;72:927-33.  Back to cited text no. 1
    
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Toma M, Buller CE, Westerhout CM, Fu Y, O'Neill WW, Holmes DR Jr, et al. Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: Insights from the APEX-AMI trial. Eur Heart J 2010;31:1701-7.  Back to cited text no. 2
    
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Panchal K, Patel S, Bhatt P. Drug-eluting stents in multivessel coronary artery disease: Cost effectiveness and clinical outcomes. Adv Pharmacol Sci 2012;2012:679013.  Back to cited text no. 3
    
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Corpus RA, House JA, Marso SP, Grantham JA, Huber KC Jr., Laster SB, et al. Multivessel percutaneous coronary intervention in patients with multivessel disease and acute myocardial infarction. Am Heart J 2004;148:493-500.  Back to cited text no. 4
    
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Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Clinical end points in coronary stent trials: A case for standardized definitions. Circulation 2007;115:2344-51.  Back to cited text no. 5
    
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Rodriguez AE, Baldi J, Fernández Pereira C, Navia J, Rodriguez Alemparte M, Delacasa A, et al. Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II). J Am Coll Cardiol 2005;46:582-8.  Back to cited text no. 7
    
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Serruys PW, Ong AT, van Herwerden LA, Sousa JE, Jatene A, Bonnier JJ, et al. Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: The final analysis of the arterial revascularization therapies study (ARTS) randomized trial. J Am Coll Cardiol 2005;46:575-81.  Back to cited text no. 8
    
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Serruys PW, Ong AT, Morice MC, De Bruyne B, Colombo A, Macaya C, et al. Arterial revascularisation therapies study part II – Sirolimus-eluting stents for the treatment of patients with multivessel de novo coronary artery lesions. EuroIntervention 2005;1:147-56.  Back to cited text no. 9
    
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Rodriguez AE, Grinfeld L, Fernandez-Pereira C, Mieres J, Rodriguez AM, Berrocal D, et al. Revascularization strategies of coronary multiple vessel disease in the drug eluting stent era: One year follow-up results of the ERACI III trial. EuroIntervention 2006;2:53-60.  Back to cited text no. 10
    
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From AM, Al Badarin FJ, Cha SS, Rihal CS. Percutaneous coronary intervention with drug-eluting stents versus coronary artery bypass surgery for multivessel coronary artery disease: A meta-analysis of data from the ARTS II, CARDia, ERACI III, and SYNTAX studies and systematic review of observational data. EuroIntervention 2010;6:269-76.  Back to cited text no. 11
    
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Eagle KA, Guyton RA, Davidoff R, Edwards FH, Ewy GA, Gardner TJ, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: Summary article. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to update the 1999 guidelines for coronary artery bypass graft surgery). J Am Coll Cardiol 2004;44:e213-310.  Back to cited text no. 12
    
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Poulin F, Rinfret S, Gobeil F. Potential shift from coronary bypass surgery to percutaneous coronary intervention for multivessel disease and its economic impact in the drug-eluting stent era. Can J Cardiol 2007;23:1139-45.  Back to cited text no. 13
    
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Palmerini T, Biondi-Zoccai G, Della Riva D, Mariani A, Sabaté M, Smits PC, et al. Clinical outcomes with bioabsorbable polymer- versus durable polymer-based drug-eluting and bare-metal stents: Evidence from a comprehensive network meta-analysis. J Am Coll Cardiol 2014;63:299-307.  Back to cited text no. 14
    
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Pilgrim T, Heg D, Roffi M, Tüller D, Muller O, Vuilliomenet A, et al. Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): A randomised, single-blind, non-inferiority trial. Lancet 2014;384:2111-22.  Back to cited text no. 15
    
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Rajasekhar D, Vanajakshamma V, Shashank C, Srinivasakumar M, Sivasankara C. The real world experience of the biodegradable polymer coated sirolimus eluting coronary stent system. Catheter Cardiovasc Interv 2014.  Back to cited text no. 16
    
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Rajasekhar D, Vanajakshamma V, Babu S, Sivasankara C, Thakkar A. Clinical outcomes from unselected real-world patients with acute myocardial infarction receiving biodegradable polymer coated sirolimus-eluting stents. J Cardiol Ther 2013;1:64-70.  Back to cited text no. 18
    
19.
Karbassi A, Kassaian SE, Poorhosseini H, Salarifar M, Jalali A, Nematipour E, et al. Selective versus exclusive use of drug-eluting stents in treating multivessel coronary artery disease: A real-world cohort study. Tex Heart Inst J 2014;41:477-83.  Back to cited text no. 19
    
20.
Xu B, Yang Y, Han Y, Li B, Liu Q, Zhu G, et al. TCT-607 clinical outcome in chinese patients with long lesion or small vessel/multivessel disease receiving XIENCE V everolimus-eluting stent: Early results from the SEEDS study. J Am Coll Cardiol 2012;60:B176.  Back to cited text no. 20
    
21.
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22.
Kornowski R, Mehran R, Satler LF, Pichard AD, Kent KM, Greenberg A, et al. Procedural results and late clinical outcomes following multivessel coronary stenting. J Am Coll Cardiol 1999;33:420-6.  Back to cited text no. 22
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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