Maximizing the safety and effectiveness of revascularization of the coronary arteries has been the aim of coronary interventional treatment since the development of percutaneous intervention. ^[1] An efficient approach of treating coronary heart disease is PCI. PCI is widely used to treat difficult lesions including diffuse, calcified, and other complex lesions.^[2] Early DES were less trackable and delivered across the lesion due to their shorter length and larger (120 mm) struts; these DES were subsequently replaced with stents with thinner struts made of biodegradable polymer.^[3] The present low strut DES has demonstrated to have a higher efficacy/safety profile in the treatment of simple as well as complex coronary disease using percutaneous coronary angioplasty (PCI) compared to the prior thick strut drug eluting stent (DES).^[3,4]

Standard DES designs feature a metallic platform and a drug polymer that is biocompatible and degradable.^[5] Durable polymer has been linked to neoatherosclerosis, delayed arterial healing, and extremely late stent thrombosis.^[6,7] These are highly prevalent in the Indian population, where 30% to 50% of patients with coronary artery multivessel disease exhibit small vessel ailment.^[8] It prompted the development of new generations of reduced strut thickness DES, which might conceivably resolve these problems.^[9] The goal of this trial was to assess the effectiveness and safety of the M’Sure-S, Sirolimus Eluting Coronary Stent System (Multimedics LLP) in the treatment of coronary artery disease. This has an ultra- low thin strut thickness of 59µm cobalt chromium platform, stent recoil of <3% and fore shortening of <0.29%.

The retrospective data of 350 subjects were collected from Sudha Hospital, who got implanted with M’Sure-S stent by Dr. Rajasekhar during the period from 2019 till 2022. These subjects were contacted by telephone to check the follow up visit data. The retrospective data is captured in the PMCF checklist – MM SES -PCH from the source data at the hospital. The telephonic visit details are recorded in Case Report Form (MM-SES-CRF) by the study team from Sudha hospital. The Ethical approval was received from the Sudha Hospitals Institutional Ethics Committee. The trial is registered in Clinical trial Registry India (CTRI).

Participants in the Study

Subjects of age >18 years with ischemic heart disease due to coronary artery lesion eligible for Percutaneous Transluminal Coronary Angioplasty (PTCA) who got implanted with M’Sure-S, Sirolimus Eluting Coronary Stent were included in the study. Subjects who are ineligible for PTCA, known allergies to L605 Chromium cobalt, contraindicated for anti-coagulant therapy, history of GI Bleed, recent CVA, diabetic hemorrhagic retinopathy, past transplant cases, with diffuse disease were excluded from the study.

Description of the study stent

The Multimedics LLP, CE approved M’Sure-S, Sirolimus Eluting Coronary Stent Systems are manufactured from L-605 Cobalt Chromium (Co-Cr) alloy are coated with a mix of biodegradable polymer and anti-restenotic drug (Sirolimus) to cater the design requirements of diameters 2.25 mm to 4.0 mm and lengths 08 to 48mm and are mounted on Tamarin Blue Rapid Exchange Delivery System. It has a stent mounted balloon near the distal tip. The balloon has two radiopaque marker bands to aid in positioning the balloon in the PCI procedures. The distal section of catheter is dual lumen and coaxial. The outer lumen is used for inflation of the balloon with contrast medium, and the inner lumen permits the use of guide wires

≤0.014 inches (0.35 mm) to facilitate advancement of the catheter to and through the stenosis or stent to be dilated. The catheter’s tip is tapered to facilitate advancement of the catheter to and through the stenosis or stent.

The effective length of the Sirolimus Eluting Coronary Stent System is 141 - 142 cm. Marks on the proximal portion of the catheter shaft indicate the exit of the balloon catheter tip out of the guide catheter (one at 90 cm and two at 100 cm). Radiopaque marker bands, in conjunction with fluoroscopy, aid in the placement of the catheter’s balloon segment. All Sirolimus Eluting Coronary Stent System sizes have two radiopaque marker bands. Sirolimus Eluting Coronary Stent Systems are intended for use in the treatment of patients with clinical symptoms of myocardial Ischemia, related to the pathological condition of one or more coronary arteries. Recognized use of Intra Vascular coronary Stents currently includes but is not limited to the treatment of de-novo or restenotic lesions in native coronary arteries and in de-novo lesions of saphenous vein grafts.

Interventional Procedure

PCI was performed following standard technique and pre-dilatation step was done in each case with a suitable rapid- exchange PTCA balloon dilatation catheter. Once a visual assessment of the vessel diameter and lesion characterization had been completed, an M’Sure-S, SES was deployed. All the patients received dual antiplatelet therapy (DAPT) (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 12 months) after the procedure. A successful device implantation with a residual stenosis of less than 20% of the vessel diameter, an event-free sheath removal, and subsequent hospital discharge were considered successful procedures.

Study Endpoints

The Primary safety endpoint of the study was to observe any undesirable adverse cardiac events in the subjects and included to analyse the residual risks during the follow-up of the study. It means the occurrence of vessel blockage, Arterial perforation/ rupture, occlusion of coronary artery, stent embolism, etc. Secondary endpoints were to understand and record the clinical outcomes that are associated/ correlated with the survival rate (life span) of the Sirolimus Eluting Coronary Stent System that is implanted in the subject population and to ensure the continued acceptability of benefit – risk ratio.

Data Collection & Statistical Evaluation

The retrospective data is captured in the PMCF checklist – MM SES -PCH from the source data at the hospital. The telephonic visit details are recorded in Case Report Form (MM-SES-CRF) by the study team from Sudha hospital. The data from PMCF checklist and the case report from were transferred to a clinical data sheet and the data is analysed by the statistician from CRO using SPSS statistics vr 28 and MS excel.

A total of 350 subject’s data was analysed and out of 26 subjects (7%), 90 subjects (26%), 129 subjects (37%), 77 subjects

(22%), 25 subjects (7%) and 3 subjects (1%) were recruited from the age groups, 30-40, 40-50, 50-60, 60-70, 70-80, and

80-90 years respectively. ^[10] The mean age was 55.83 ± 10.34 years. 291 patients, 83.14% of patients were male and 59 patients, 16.85% of patients were females.^[11] In the total cohort, 48 (13.71%) patients had a history of smoking, 18 (5.14%) patients had a history of alcohol consumption and comorbidities such as hypertension and diabetes mellitus were present in 101 (28.85%) and 256 (73.14%) patients, respectively. The baseline demographics of patients are shown in Table 1.

Table 1. Baseline demographics

Lesion and procedural characteristics

In 350 patients, there were a total of 521 lesions. Out of these, 459 lesions were treated with M’Sure-S SES (1.31 stents per patient). A total of 195 (55.71%) patients had single-vessel disease, 110 (31.42%) had double-vessel disease and 45 (12.85%) had multiple vessel disease. Total number of study stents deployed were 396. The most common target vessel was the left anterior descending artery in 224 (64%) patients followed by right coronary artery in 88 (25.14%) and left circumflex artery in 20 (5.71%) patients. ^[12] The mean lesion length and diameter was 31.37 ± 14.56 mm and 2.9 ± 0.3 mm, respectively. The average length and diameter of the study device was 31.57 ± 14.65 mm and 3.1 ± 0.25 mm, respectively. The majority of the patients were prescribed ticagrelor 309 (88.28%) followed by clopidogrel 35 (10%), and prasugrel 6 (1.71%).^[13] The lesion and procedural characteristics were shown in (Table 2).

Table 2. Lesion and Procedural Characteristics

Clinical outcomes through 3-year follow-up

The cumulative incidence of MACE at 3-year follow-up was 1 (0.2). The cumulative deaths due to cardiac causes at 3- year follow-up was zero. The cumulative deaths due to non-cardiac causes at 3-year follow-up was 5 (1.4%). There was no case of TLR or TVR at 3-year follow-up. There were three (0.3%) incidences of probable ST as per ARC definitions during the 3-year follow-up and no new cases were reported during the subsequent follow-up period. The Cumulative MACE at 3-year follow-up were shown in (Table 3).

Table 3. Cumulative Major Adverse Cardiac Events at 3-year Follow-Up

Values are expressed as n (%). MACE is defined as a composite of cardiac death, myocardial Infarction (MI) attributed to target vessel and target lesion revascularization. ST: stent thrombosis; TLR: target lesion revascularization; TVR: target vessel revascularization; MI: myocardial infarction; TVMI: target vessel myocardial infarction.

Subgroup analysis

A subgroup analysis was carried out to compare the rate between the long stent (≥ 40 mm) and short stent length (< 24 mm) groups. The comparison of M’Sure-S stent lengths was shown in (Table 4). The comparison of M’Sure-S stent diameters was shown in (Table 5).

Table 4. Comparison of M’Sure-S Stent Lengths

Table 5. Comparison of M’Sure-S Stent Diameters

Clinical Safety Monitoring Parameters like Restenosis, Infection or pain at the insertion site, Allergic reaction, Vascular complications, Drug reaction to antiplatelet agents, Chest pain or shortness in breathing were not reported in 350 subjects. The known risks from the product which are identified in our Risk Management file as well as from published literature sources were included for analysis.^[14] As per the analysis, there were no new risks identified for the Sirolimus Eluting coronary stent system. Hence, we conclude that no additional risks were imposed by the product.^[8]

No adverse events were reported for the 350 subjects who had undergone implantation using Sirolimus eluting coronary stent system. The outcome of the Implantation of M’Sure-S stent is evaluated and observed that the implantation is successful in the 350 subjects in this study as well as others too in his experience. All the subjects got their cardiac output improved after the implantation.^[15]

The clinical safety and performance are measured as qualitative responses during the telephonic follow up visit of the population who responded during the call made by the study team from Sudha Hospital. The mortality rate in 350 population who got implanted with Sirolimus Coronary stent system is 1.42% (5 subjects). These subjects had passed away in this study period however the reason of death is not known. Hence the remaining 345 subjects were included in the post- operative result. After reviewing all the parameters, it is obvious that there were no events or safety issues reported in these subjects whom the telephonic follow up was made. The 345 subjects follow up data was collected.

Complications and other pathologies

None of these complications had been reported in 345 subjects who were available for telephonic follow up.^[7] The summary of complications, pathologies, Adverse events and Residual Risks were shown in (Table 6).

Table 6. Complications and Pathologies

Quality of Life

Out of 345(100%), 2 (0.6%) of the subject population had faced discomfort after the stent implantation, these subjects had revisited the hospital due to breathing difficulty. It was observed that they never came for any regular checkups and the medical therapy was not revised in them since they refused to visit hospital due to Pandemic situation. Out of 345 (100%), 3 (0.9%) of the subject population had faced chest pain or shortness of breath after the implantation of stent and those subjects never came for any regular checkups and the medical therapy was not revised in them since they refused to visit hospital due to Pandemic situation. None of the subjects reported any recurrence of heart attack or heart failure after the implantation of stent. Out of 345(100%), 1 (0.3%) of the subject population had undergone re-angioplasty, this re- angioplasty was performed at different site in the coronary artery and the existing stent was performing well in that subject.^[13]

Out of 345 (100%), 2 (0.6%) of the subject population had taken new medications after the surgery which was or non- related cardiac issues. Out of 345 (100%), 4 (1.1%) of the subject population faced difficulties while doing exercise or any physical activity, these subjects have not done any follow up visits, these subjects were asked to come back for a checkup during a telephonic follow up visits. Out of 345(100%), 1(0.3%) of the subject population found difficulties that were experiencing before stent placement occurring even after the surgery.^[16] These subjects have not done any follow up visits, the subjects were asked to come back for a checkup during a telephonic follow up visits. Out of 345 (100%), 1 (0.3%) of the subject population had faced difficulty after the stent placement. These subjects have not done any follow up visits, the subjects were asked to come back for a checkup during a telephonic follow up visits. All the 345 (100%) subjects reported they are satisfied with the product. The Quality-of-Life parameters and results were shown in (Table 7) and the Quality- of-Life improvement scale was shown in (Figure 1).

Table 7. Quality of Life

Health condition before and after surgery

The overall health and the discomfort in chest and doing activities were assessed during the post implantation visit. All of them confirmed the discomfort is reduced to nil. The rate of the health condition before and after surgery was shown in (Table 8).

Table 8. Rate of the health condition before and after surgery

M’Sure-S, SES treated a total of 350 patients included in this retrospective study. Construction of M’Sure-S, SES consist an ultra-low thin cobalt-chromium platform and intelligent cell design comprising of open and closed cells provide optimal radial strength, high degree of flexibility & excellent Scaffolding. The special electro-polishing technique ensures an ultra- low strut thickness of 59μm.^[9]

Results of the current study stated that, in CAD patients during follow-up, the M’Sure-S, SES exhibited favourable clinical safety and performance in the management of coronary artery multivessel disease.^[17]

Demographic data showed Less than 1% of the subject population had experienced adverse events other subjects never had experienced any adverse events or side effects. Out of 345(100%), 2(0.6%) of the subject population had faced discomfort after the stent implantation where these subjects did not come for any follow-up visits post procedure. 332 subjects responded that totally the quality of life is improved, remaining 11 also confirmed mostly their quality of life is improved. 99.6% of the subject population had improved their quality of life.^[13] Several meta-analyses have also reported reduced rates of Target Lesion Failure with ultrathin DES (strut thickness <70 μm) compared to contemporary thicker strut DES at short-term (1 year) and even at long-term (mean 2.5 years) follow-up.^[9,15] An article published the meta-analysis report which demonstrated that reduce rate of device oriented composite events by 11% with ultrathin strut DES compared to thicker strut DES at a maximum follow-up of three years.^[5] Lack of complete strut coverage and optimal healing have been strongly associated with the incidence of late stent thrombosis. The prime determinant factor for the duration of strut coverage after stent implantation is strut thickness.^[18]

Various studies have reported that thinner struts provide complete endothelial coverage with rapid healing and thus may lessen the risk of platelet aggregation and stent thrombosis. In support to these, the present registry reported 99.6% of the subject population had improved their quality of life with ultrathin M’Sure-S, SES at the follow-up.^[14] Hence, M’Sure-S, SES in consecutive patients for the treatment of CAD was carried out as retrospective observational study to evaluate clinical outcomes. The most convincing clinical results of this retrospective study are 100% procedural success rate. Moreover, <1% cardiac adverse events. M’Sure-S, ultra-low thin strut (59 µm) SES has already been proved as a most deliverable DES and as efficacious as standard of care DES.^[19] The study results are as summarised below:

We clinically investigated all the 350 subjects to review through Clinical Study data. As per the study, the M’Sure-S, Sirolimus eluting coronary stent system have met the primary and secondary objectives. The primary objective of confirming clinical performance and safety throughout the expected lifetime of the medical device the acceptability and to assess the Safety and Performance of the Sirolimus Eluting coronary stent system were proved by this post market clinical study and the results were outlined. Any undesirable adverse events under normal condition were observed. The results outlined proves the secondary objective of determining any undesirable events under normal condition of use and assess whether the risks outweigh the intended benefits of the device. The Sirolimus Eluting Coronary stent system from Multimedics LLP has reached all the safety and performance requirements with respect to the intended use of the Device from the retrospective clinical study. The clinical evidence is demonstrated with the relevant GSPR. There were no new risks identified from the study for the product hence there is no addition to the residual risks which we have already identified in the Risk Management Report and that is been mitigated and are acceptable when weighed against the benefits to the patient. The results of this study on wide range of complex and heterogenous patient population all around the globe will take it closer towards the title of an ideal DES for all sorts of patients.