|Year : 2022 | Volume
| Issue : 3 | Page : 130-137
Outcomes of supraflex Sirolimus-eluting coronary stents
Vishal Virendra Singh1, Sheikh Mohamad Tahir2, Sanjiv Sharma3
1 Department of Cardiology, Apusnova Multi-Super Speciality Hospital, Meerut, Uttar Pradesh, India
2 Department of Cardiology, Super Speciality Hospital, GMC, Srinagar, Jammu and Kashmir, India
3 Batra Hospital and Medical Research Centre, New Delhi, India
|Date of Submission||04-Mar-2022|
|Date of Decision||23-Apr-2022|
|Date of Acceptance||01-May-2022|
|Date of Web Publication||01-Aug-2022|
Dr. Sheikh Mohamad Tahir
Super Speciality Hospital, GMC, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
Background: The development of a sirolimus-eluting coronary stent (SES) was a big step forward in interventional cardiology. SES has been demonstrated in large, randomized clinical studies to reduce angiographic restenosis and target vessel revascularization (TVR) when compared to bare-metal stents and other drug-eluting stents (DESs). However, there is little information on the outcomes of Indian patients treated with Drug-eluting stents (DES). As a result, the study's goal was to assess the efficacy of Supraflex sirolimus-eluting coronary stents in the treatment of coronary artery disease and to identify severe adverse cardiovascular and cerebrovascular events. Methods: This single-center, observational, nonrandomized study enrolled unselected real-world patients at a tertiary care center who had undergone implantation with Supraflex sirolimus-eluting stents. The primary endpoint of the study was major adverse cardiovascular and cerebrovascular events (MACCE), which is a conglomeration of cardiac death, target lesion revascularization, TVR, cerebrovascular accident (CVA), and heart failure at 1-year follow-up. Results: A total of 100 patients were intervened successfully with sirolimus-eluting stents. Out of total patients, diabetes and hypertension were observed in 38% and 35% of patients, respectively. According to the American College of Cardiology/American Heart Association classification, there were 68% of type B lesions and 32% of type C lesions. At 1-year follow-up, major adverse cardiovascular events were 11%, a composite of 4% target lesion revascularization, 3% target vessel revascularization, 1% CVA, and 5% heart failure. Diabetes (P = 0.02), hypertension (P = 0.01), kidney dysfunction (P = 0.002), and left ventricular (LV) function (P = 0.01) strongly correlated with outcome (MACCE). Conclusion: There was an acceptable rate of adverse events after implantation of the Supraflex sirolimus-eluting stents, although slightly higher than in other studies. Diabetes, hypertension, kidney dysfunction, and LV function strongly correlate with the outcome (MACCE).
Keywords: Acute coronary syndrome, drug-eluting stents, percutaneous coronary intervention outcomes, percutaneous coronary intervention
|How to cite this article:|
Singh VV, Tahir SM, Sharma S. Outcomes of supraflex Sirolimus-eluting coronary stents. Curr Med Issues 2022;20:130-7
| Introduction|| |
Since Andreas Gruentzig's invention of percutaneous coronary intervention (PCI) in 1977, the treatment of coronary artery disease (CAD) has been radically transformed., Balloon angioplasty and coronary stenting have had a considerable impact on the treatment of both stable and unstable CAD. Although the initial results of percutaneous balloon angioplasty were encouraging, there was concern about periprocedural complications such as plaque rupture and coronary dissection, which are frequently clinically translated into acute myocardial infarction (MI), particularly in the days following the procedure. Emergency coronary artery bypass grafting (CABG) was common due to acute vascular closure due to dissection. Furthermore, during follow-up, the advantages of revascularization were further offset by the high frequency of restenosis, which might approach 40%. More than a million patients are treated with PCI every year in the USA, often for nonacute CAD.
Several trials demonstrated a significant reduction in restenosis, and target vessel revascularization (TVR) in patients assigned to bare-metal stent (BMS) implantation compared to those assigned to percutaneous transluminal coronary angioplasty (PTCA) demonstrated the beneficial angiographic and clinical effects of stents (PTCA). By providing a mechanical framework to maintain radial support and limiting elastic recoil, BMSs lowered restenosis rates from 30%–40% in the balloon angioplasty period to 20%–25%., The capacity of coronary stents to minimize elastic rebound and unfavorable negative vasculature remodeling that occurs after balloon dilation is primarily responsible for their benefit in minimizing the incidence of restenosis following PCI.
However, with the widespread use of BMS, two notable complications emerged: in-stent restenosis and stent thrombosis. Although stent thrombosis was significantly reduced with helpful antiplatelet therapy after stent implantation, in-stent restenosis remains a challenge. In-stent restenosis is a more superficial, more straightforward reaction to the coronary intervention resulting from an excessive proliferative neointimal response. In the pathophysiology of in-stent restenosis, there are four clears but overlapping components: platelet deposition, leukocyte recruitment, smooth muscle cell migration, and proliferation and matrix deposition. While the risk of developing in-stent restenosis is linked to various clinical and procedural factors (particularly diabetes, long lesions, small vessels, and procedural failure), all BMS, regardless of the thickness of the struts, provoke a considerable proliferative response.
First-generation drug-eluting stents (DESs) were designed to target in-stent restenosis caused by neointimal hyperplasia. To this end, coronary artery stents were coated with a polymer allowing controlled local delivery of a pharmaceutical agent with antineoplastic and anti-inflammatory properties. Subsequently, DESs replaced BMSs in most PCI procedures. However, as the use of DESs expanded beyond the well-studied indications of the randomized controlled trials, concern arose regarding the safety profile of the first-generation DES.,,
DES was based on the concept of local drug release at the site of tissue injury to resist smooth muscle proliferation. The astonishing results of the first studies performed with rapamycin- and paclitaxel-eluting stents confirmed the concept that a high local concentration was essential to control the excessive proliferative response.
First-generation drug-eluting stents
Sirolimus, a naturally occurring macrolide, has powerful antiproliferative, anti-inflammatory, and immunosuppressive properties. It is also known as rapamycin since it was discovered to be generated by a bacteria in an Easter Island soil sample (also known as Rapa Nui). The antirestenotic characteristics of sirolimus are mediated by binding to the FK506-binding protein 12 (FKBP12); the sirolimus/FKBP12 combination causes the cell cycle to halt in the G1 phase by inhibiting mTOR, an important cell cycle regulatory protein.,, A patient-level pooled meta-analysis of these studies found that using the Cypher SES versus BMSs resulted in a permanent decrease in repeat revascularization with no increase in mortality, MI, or stent thrombosis. Supraflex stents are composed of a Millennium Matrix stent, sirolimus medication, and a totally biodegradable polymer covering. Sirolimus has a dual mode of action in that it controls inflammatory cell activity when also inhibiting smooth muscle cell growth. Even with smaller struts, the innovative design and strut locking mechanism provide outstanding radial strength and little rebound. The smooth surface, round edges, and thin struts of the stent help reduce vascular damage and thrombus development.
Paclitaxel is eluted by Taxus PES. Paclitaxel, a lipophilic chemical produced from the Pacific yew tree Taxus brevifolia, exhibits antirestenotic characteristics that limit smooth muscle cell proliferation and migration during the mitotic phase of the cell cycle. The Taxus studies indicated that the modest dosages of paclitaxel might halt the cascade of restenosis without causing harm.,,,
Next-generation drug-eluting stents
Zotarolimus is a sirolimus analog with a shorter in vivo half duration but the same high-affinity binding to the immunophilin FKBP12. In vivo trials (ENDEAVOR II) demonstrated zotarolimus-eluting stents (ZES) Endeavor™ (Medtronic, MN, US) to be superior over BMS in terms of TVR, with a similar rate of major adverse cardiac events (MACEs). In comparison to the other DESs, ZES proved to be less successful than SES but more effective than PES after 3 years of follow-up, as validated by the ENDEAVOR IV trial's 3-year findings.
Everolimus (Certican, Novartis Corporation, NJ, USA) is a sirolimus analog. It is an immunosuppressive macrolide that operates as a mTOR inhibitor after binding to FKBP12. As a result, several cell types (such as vascular smooth muscle cells) become trapped in the G1 phase of the cell cycle. The EES copolymer is made up of two layers: a priming layer and a drug–polymer reservoir layer. There is no topcoat. PBMA is used as a thin primer adhesion layer. Polybutylmethacrylate copolymer (PBMA) is used as a thin primer adhesion layer and the drug–polymer reservoir layer consists of polyvinylidene fluoride-co-hexafluoropropylene blended with everolimus in an 83/17 polymer/everolimus ratio by weight. The copolymer coating is about 8 m thick and is applied to the stent's luminal and abluminal surfaces. Because it is lubricious and nonsticky, it will not attach to the stent delivery balloon or struts. DES has shown a tremendous promise in recent years, and numerous stents containing various types of medicines have been tried. Some drugs, such as paclitaxel, can be directly coated on a metal stent. The bulk of medications, on the other hand, must be connected to a polymer that functions as a drug reservoir. With this goal in mind, we undertook a trial to evaluate the efficacy of Supraflex sirolimus-eluting coronary stents for the treatment of CAD. The study's goals were to identify serious adverse cardiovascular and cerebrovascular events such as TVR, target lesion revascularization (TLR), cerebrovascular accident (CVA), cardiac mortality, and heart failure.
This was a longitudinal study.
The study was undertaken in the cardiology department of cardiology, Batra hospital and medical research center in New Delhi.
Study participants and duration
All consecutive patients who had undergone PCI with Supraflex sirolimus-eluting coronary stents in our hospital from May 2019 to May 2020 recorded in our coronary intervention registry were enrolled in the study. The sample size was calculated based on the previous analysis, in which the prevalence of CAD was 11%. Considering the significance level at 5% and the margin of error at 10%, a sample size of 40 was calculated, which was considered sufficient for our study. However, we planned to include 100 patients.
Inclusion and exclusion criteria
We included patients who had undergone coronary artery stenting with Supraflex sirolimus-eluting stent for any of the following reasons: (a) patients who had stable angina, (b) patients who had unstable angina, (c) patients who had ST-elevation MI or non-ST-elevation MI, and (d) all such patients who had single vessel/multivessel disease on coronary angiography and who underwent coronary artery stenting with Supraflex sirolimus-eluting stents. We excluded those patients who had undergone coronary artery stenting other than Supraflex sirolimus-eluting stent.
The patients' baseline clinical and coronary artery lesion characteristics were recorded as available in the records and summarized as per the protocol drafted for the study. Clinical follow-up of all these patients was done at 6 months and 1 year after the index procedure. The following measures were carried out:-
- We selected patients who visited the follow-up clinics. Their status was recorded by clinical history, physical examination, laboratory tests, and coronary angiography if required and indicated
- Patients who do not report for the following were telephonically interviewed. For this, a questionnaire was drafted and validated.
Variables used in the study
MACE is applied to major adverse cardiovascular events. The SPIRIT trials used MACE as an endpoint in their study, and we planned to do the same. Major adverse cardiac vascular events were described as death; all deaths were considered cardiac unless documented otherwise. MI was defined as an elevation of troponin above the upper range limit in combination with at least one of the following: symptoms of ischemia. Electrocardiography changes indicate new ischemia (ST wave changes or new left bundle branch block [LBBB]) or the development of pathological Q waves on electrocardiography., The ST-T wave changes indicative of further ischemia were followed. Target vessel revascularization was defined as repeat revascularization of a lesion in the same epicardial vessel treated in the index procedure. Target lesion revascularization: TLR was described as a repeat intervention in the stent or within 5 mm proximal or distal to the stent or CABG of the target vessel.
TVR and TLR were available only if follow-up CAG was done.
We planned to look for major adverse cardiovascular and cerebrovascular events (MACCE).
- Angiographic success is defined as residual stenosis <20% in the presence of thrombolysis in MI flow grade 3
- The coronary lesions are classified as per the American Heart Association/American College of Cardiology guidelines for percutaneous coronary angioplasty
- Hypertension is defined as blood pressure >140/90 mmHg or the use of antihypertensive medications
- Stent thrombosis is defined as “acute” if within 24 h of the procedure, “subacute” at 1–30 days, and “late” after 30 days. The definition of ST is by the Academic Research Committee definitions of definite, probable, and possible ST)
- Electrocardiogram manifestations of acute myocardial ischemia (in the absence of LBBB or left ventricular hypertrophy) ST-elevation.
New ST elevation at j point in two contiguous leads with the cut off points; ≥0.2 mV in men and ≥0.15 mV in women in leads V2–V3 and ≥0.1 mV in other charges.
ST depression and T wave changes.
New horizontal or downsloping ST depression ≥0.05 mV in two contiguous leads, T inversion ≥0.1 mV in two contiguous leads with prominent R wave or R/S ratio.
Statistical method used
A categorical variable was expressed as frequency and proportions (%) and a continuous variable as mean ± standard deviation or median (inter quartile range), when skewed in distribution. The continuous variable was compared using a t-test. The categorical variable was compared using Fisher's exact or Chi-square test. The study was compared with similar studies in the literature and analyzed statistically using P < 0.05 as statistically significant. The data were tabulated in the MS Office Excel worksheet. Descriptive statistics were computed for all the numerical data. All statistical analyses were performed using the Statistical Package for the Social Sciences IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.
Institutional ethics committee
This study design, tools for data collection, consent forms, and patient information sheets were reviewed by the institutional ethics committee at our institute as a part of the procedure involved for all researches requiring human participation. The study was conducted after the approval of the Institutional Ethics Committee vide order No. B. H./23/2018.
| Results|| |
From May 2019 to May 2020, all patients who underwent PCI with Supraflex sirolimus-eluting coronary stents in our facility were serially enrolled. For this investigation, a total of 108 patients were recruited. During the follow-up period, eight patients died. All patients were handled in accordance with conventional treatment recommendations and were discharged on approach-driven medical therapy. One year following the index surgery, these 100 patients were given a 6-month clinical follow-up. The patients' ages varied from 45 to 78 years, with a mean age of 62.32 ± 6.6 years, and male patients predominated with 62% of the overall sample, as shown in [Table 1].
In our study, 35% of patients were hypertensive, 38% had diabetes, 52% had a history of tobacco consumption, 2% had a history of CABG, 6% had a history of the previous PCI, and 6% had a history of MI and had not been treated with any revascularization procedure. Furthermore, in our study, 81% of patients had no signs of renal impairment, 14% had stage 1 kidney disease, 4% had stage 2 kidney disease, and 1% had stage 3 kidney disease [Table 2].
About 61% of patients had normal left ventricular (LV) function, 23% had mild LV systolic dysfunction, 13% had moderate LV systolic dysfunction, and 3% had severe LV systolic dysfunction. The most common form of presentation for systolic dysfunction was unstable angina (33%), followed by anterior wall ST-elevation myocardial infarction (STEMI) (23%). [Table 3] shows that stable angina was the mode of presentation in 21% of patients, inferior wall STEMI was shown in 13%, and non-ST-elevation myocardial infarction (NSTEMI) was presented in 10% of patients.
|Table 3: Mode of presentation to the cardiac physician/emergency room found among the studied patients|
Click here to view
[Table 4] shows the procedural and angiographic features of the individuals investigated. The majority of the patients, 68%, had type B lesions, whereas 32 had type C lesions. The majority of patients, 46%, had double-vascular disease, whereas 44% had the single-vessel disease. Triple-vessel disease was seen in 10% of the patients. The most common vessel stented was left anterior descending (LAD) > right coronary artery > left circumflex (LCX); Graft's vessel was stented only in (1.6%). None of our study patients has bifurcation or left primary stenting. Single-vessel stenting was done in 78% of cases, whereas multivessel stenting was done in 22% of cases.
|Table 4: Procedural and angiographic characteristic among the studied patients|
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The mean stent length of the first stented vessel was 26.6 ± 6.01 mm, and the mean stent diameter was 3.01 ± 0.37 mm, whereas the mean stent length of the second stented vessel was 20.4 ± 3.2 mm, and the mean stent diameter was 2.86 ± 0.24 mm. In addition, 3% of patients needed intra-aortic balloon pump support, 3% needed TPI support, 4% needed inotropic support, and 3% needed defibrillation.
[Table 5] summarizes the treatment outcomes of the individuals investigated. In 93% of cases, the procedure was simple. Two patients experienced slow flow. Two individuals had CIN, which was treated medically under the supervision of a nephrologist. Flow-limiting dissections occurred in 3% of the cases, and they were all collected with a stent. There was no fatality, stroke, or MI during the procedure. One patient who presented with NSTEMI 4 months later exhibited angiographic signs of in-stent restenosis. Therefore, his target lesion revascularization was done.
About 7% of patients reported poststenting angina, with six patients undergoing stress imaging and four demonstrating signs of ischemia. These four patients received repeat coronary angiography, and two of them were discovered to have in-stent restenosis and underwent TLR. One patient was discovered to have a new illness in the same artery and had target vessel revascularization.
On stress imaging, the other two patients were determined to have no indication of proven myocardial ischemia and were handled with therapy optimization. One of the patients was discovered to be highly anemic. Her symptoms improved once her anemia was corrected. In the first 6 months, two patients suffered cardiac failure; one underwent TVR, while the other was handled with a medication adjustment. At 4 months, one patient experienced an ischemic stroke, which was largely recovered on follow-up.
Between 6 and 12 months, three more patients presented with poststenting angina, all of them subjected to stress imaging, out of which one patient had evidence of provocable ischemia, underwent coronary angiography, and was found to have a proof of in-stent restenosis, hence underwent target lesion revascularization. The other two patients were found to have no evidence of provable ischemia on stress imaging managed with optimization of treatment. A total of three patients had developed heart failure between 6- and 12-month duration, out of which one patient underwent target vessel revascularization. The rest two were managed with an optimization of treatment.
No additional CVA and death occurred in the 6–12-month follow-up. At the end of 1 year, the incidence of TLR was 4% and TVR 3%. One patient developed CVA at 4-month postprocedure. No cardiac death or stent thrombosis occurred during the entire follow-up. A cumulative MACCE rate was 11%. The incidence of MACCE in different subgroups of the studied patients is described in [Table 6]. Age and sex did not affect MACCE in our cohorts. Diabetes, hypertension, kidney dysfunction, and LV function strongly correlate with the outcome (MACCE). At the same time, the length of the stent, the diameter of the stent, and the type of lesion did not affect MACCE in our cohorts.
|Table 6: Incidence of major adverse cardiovascular and cerebrovascular event in different subgroups of the studied patients|
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| Discussion|| |
The introduction of SES was a big step forward in interventional cardiology. Large, randomized clinical studies using SES have revealed a significant reduction in angiographic restenosis and TVR when compared to BMSs, with equivalent outcomes to other DESs. Evidence from common practice and noncontrolled clinical studies appears to corroborate these experiments as well.
However, there is a lack of data on the outcomes of Indian patients treated with DES; hence, the purpose of this study is to assess the performance of an Indian origin sirolimus-eluting stent (Supraflex) in the Indian population.
Our prospective observational study was conducted at a specialist tertiary cardiac center in North India. Follow-up was completed in 100 (92%) of the 108 recruited patients, while the remainder were lost during follow-up and were eliminated from the research.
The mean age of our study patients was 62.326.6 years, which is comparable to previous Indian research. In a survey conducted by Seth et al., the average age was 58.10 years; in a study conducted by Lemos et al., the average age was 61.6 ± 10 years. Patients' age ranged from 45 to 78 years, with the majority being between the ages of 55 and 75.
The proportion of male patients in our study was 62%, which is consistent with the proportion of male patients in other Indian and Western studies.
The prevalence of diabetes was 38%, which is comparable to the study of Seth et al. at 39%, slightly higher compared with the study of Lemos et al. at 23%, prevalence of hypertension was 35% which is somewhat lower as compared to studies of Seth et al. and Lemos et al. Finally, the history of tobacco abuse was 52% in our study cohort, higher than the study of Seth et al., 30%, and Lemos et al. was 7.1%.
Kidney injury was present in 19% of our patients, out of which 14% of patients were in stage 1, 4 in stage 2, and 1 in stage 3. Seth et al.'s study excluded patients with impaired renal function.
In our study, 23% of patients had mild LV systolic dysfunction, 13% had moderate LV systolic dysfunction, and 3% had severe LV systolic dysfunction. In a study by Seth et al. and Shetty et al., patients with EF <30% were excluded from the analysis.
Most of the patients in our study had type B lesion (68%), and type C lesion was present in 32% of patients, which is higher than the study of Seth et al. and lower than the study of Lemos et al. In the survey by Seth et al. type C lesion was 7%, and in the study by Lemos et al., type C lesion was 57%.
The most common target coronary artery was LAD in our study%, comparable to Seth et al. and the study of Lemos. In addition, SVG graft intervention was performed in 1.6% of cases in our survey, while in the study of Lemos et al., SVG graft intervention was performed in 1.1%.
The mean stent length was 26.6 ± 6.01 in our study, 19.72 ± 9.2 in the study of Seth et al., and 26.6 ± 9.3 in the survey of Lemos et al. The mean stent diameter was 3.01 ± 0.37 in our study and 3.1 ± 0.4 in Lemos et al.
In our study, the overall MACCE (11%), target lesion, and TVR were higher than in most of the other studies; this might be because the study of Seth et al. excluded patients' with impaired renal function and studies by Seth et al. and Shetty et al. excluded patients with severe LV systolic dysfunction.
CVA occurred in 1 patient, similar to the study of Seth et al. No death occurred during the entire follow-up period, although a high MACCE rate may be an incidental finding.
Diabetes was an essential predictor of MACCE in our study, with a 9% MACCE rate (P = 0.02). A similar trend was observed in a survey of Kuchulakanti et al.
Kidney dysfunction was also a significant predictor of MACCE in our study (P = 0.02); a similar trend was observed in a survey by Lemos et al.
Hypertension was an essential predictor of MACCE in our study, with a 10% MACCE rate (P = 0.01), although it was not directly found to be correlated in a study by Lingman et al.
LV dysfunction was also a significant predictor of MACCE in our study (P = 0.01). This was also observed in the Mamas et al.'s study.
While age, sex, stent length and diameter did not influence the 1-year MACCE rate.
The key recommendations from the study are:
- A large multicenter randomized study is needed to delineate better outcome of Indian origin stents in the Indian population
- MACCE criteria should be standardized to compare studies from different geographic regions
- Community awareness regarding lifestyle modification through information, education, and communication needs to be done.
It is a nonrandomized observational analysis with a total number of patients being small, a single-center study that can have a selection bias. We also did not look at the risk scores of the study population as it was out of the study's objectives, and study follow-up was a mere 1 year only due to protocol boundaries. The drug and antiplatelet regimen compliance of these patients to medications has not been recorded, which is a very important factor in recurrent events poststenting. Furthermore, no intravascular imaging intravascular ultrasound/optical coherence tomography was done either during initial angioplasty or among those who presented with ISR or repeat cardiac events.
| Conclusion|| |
This 1-year prospective single-center observational study for the outcome of Supraflex sirolimus-eluting coronary stents for the treatment of CAD at tertiary cardiac centers in North India showed a high MACCE rate compared to available data despite standard care of treatment. Diabetes, hypertension, kidney dysfunction, and LV function strongly correlate with the outcome (MACCE). Age, sex length of the stent, the diameter of the stent, and the type of lesion did not affect MACCE in our cohorts.
We would like to thank all the authors whose studies have been consulted when framing this manuscript. Also, We would like to thank all the patients who participated out of their own will in this study. Also, we would like to pay our regards to the staff and administration of Batra Hospital and Medical Research Centre, New Delhi, for their support during the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
This study design, tools for data collection, consent forms, and patient information sheets were reviewed by the Institutional Ethics Committee at our institute as a part of the procedure involved for all research requiring human participation. The study was conducted after the approval of the Institutional Ethics Committee vide order no B.H./23/2018.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]