In spite of the reduction of restenosis and the need for repeat revascularization with drug-eluting stents (DESs), the persistence of adverse events with first-generation durable polymer-based DES enlightens the opportunity for further improvement in DES technology [
The design and engineering of stent platforms is constantly evolving with major advancements made over the years [
This was a prospective, nonrandomized, multicenter, single-arm study which enrolled 189 patients with
Flow chart of the study.
The Supraflex SES is designed, using the Flexinnium bare-metal stent as a platform, with highly flexible “S-link” (Figure
Supraflex sirolimus-eluting stent: a schematic view of the stent structure (circle shows flexible “S-link”).
Scanning electron microscopy (SEM) images of a (a) normal, (b) crimped, and (c) expanded Supraflex sirolimus-eluting stent.
Drug release kinetics of the Supraflex sirolimus-eluting stent.
Coronary interventional procedures and adjuvant medications were performed according to standard guidelines [
Clinical data were collected before and after the index procedure and recorded in a dedicated database for all patients. Total 61 patients underwent angiographic evaluation at 9 months. Clinical/telephonic follow-up was scheduled for all enrolled patients at 30 days, 6 months, and 12 months, and collected details like assessment of angina status, monitoring of cardiovascular and antithrombotic drug use, interim hospitalisations, occurrence of major adverse cardiac events, and any invasive and noninvasive diagnostic test or interventional treatment that had occurred since the previous contact. An independent clinical events committee (CEC) reviewed and adjudicated all major adverse cardiac events.
The primary endpoint of the study was target lesion failure (TLF), including cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) during 12-month follow-up after the index procedure. Secondary endpoints included acute success (lesion success, device success, and procedural success) and in-stent late lumen loss at 9 months by QCA. Lesion success was defined as a final diameter stenosis <30% with any device with TIMI 3 flow; device success was defined as stenosis of <30% diameter with TIMI 3 flow in the absence of device malfunctions; and procedure success was defined as a final diameter stenosis <30% with TIMI 3 flow, without the occurrence of death, MI, or repeat revascularization of the target lesion during the hospital stay.
Any death was considered cardiac, unless clear noncardiac causes could be determined. MI was defined by elevation of cardiac troponin (cTn) values [>5 × 99th percentile upper reference limit (URL)] in patients with normal baseline values (≤99th percentile URL) or a rise of cTn values >20% if the baseline values are elevated and are stable or falling. TLR was defined as repeat percutaneous intervention of the stented lesion including 5 mm proximal and distal from the edge of the stent or bypass surgery of the target vessel that was performed for a clinical indication and was due to restenosis or closure of the target lesion. Target vessel revascularization (TVR) was defined as repeat revascularization by either percutaneous coronary intervention (PCI) or CABG of the target vessel. We also evaluated the incidence of stent thrombosis (ST) as a safety endpoint during 12-month follow-up period, as defined by the Academic Research Consortium (ARC) [
Angiographic assessments were performed at baseline, after procedure, and at 9-month follow-up, in two orthogonal views after the intracoronary administration of nitroglycerin. A quantitative offline coronary angiographic analysis was performed [Coronary Angiography Analysis System (CAAS, version 5.9.2); Pie Medical Imaging, Maastricht, Netherlands] with automatic edge detection by senior interventional cardiologist who had experience in reading coronary angiograms with performing QCA and was blinded to the clinical data. For every patient, in-stent (bordered by the stent margins) and in-segment (in-stent region plus 5 mm margins proximal and distal to the stent) measurements were performed by QCA. The quantitative angiographic parameters including reference vessel diameter (RVD), percentage diameter stenosis (DS), minimal lumen diameter (MLD), late luminal loss, binary restenosis, and acute gain were evaluated. Percent diameter stenosis was defined as 1 − [MLD/RVD] × 100, late luminal loss was defined as the difference between the MLD at the completion of the stenting procedure and the MLD measured at angiographic follow-up, binary restenosis was defined as a diameter stenosis of ≥50% at angiographic follow-up, and acute gain was defined as the MLD immediately after the procedure minus the MLD before the procedure.
The MANIPAL-FLEX study was designed to provide adequate preliminary data about the safety and efficacy of the Supraflex SES and was therefore considered explorative. Resulting values will be the basis for sample size calculations for future studies. Based on similar studies with other drug-eluting stent systems, a sample size of 189 patients (61 patients for angiographic assessments) was expected to be sufficient for preliminary evaluation of the safety and efficacy of the device. Data are presented using descriptive statistical methods. Continuous variables were presented as mean ± standard deviation, whereas categorical variables were expressed as percentages. All data were processed using the Statistical Package for Social Sciences, version 15 (SPSS, Chicago, IL, USA).
The baseline clinical characteristics are outlined in Table
Baseline clinical characteristics for the entire population (
Variables |
|
|
---|---|---|
Age, (mean ± SD, years) |
|
|
Male, |
136 (72.0%) | 49 (80.3%) |
|
||
|
||
Diabetes mellitus, |
58 (30.7%) | 13 (21.3%) |
Hypertensive, |
97 (51.3%) | 26 (42.6%) |
Hypercholesterolemia, |
61 (32.3%) | 18 (29.5%) |
Current smoker, |
45 (23.8%) | 11 (18.0%) |
Family history of CAD, |
12 (6.3%) | 4 (6.6%) |
Previous MI, |
13 (6.9%) | 4 (6.6%) |
Previous PCI, |
17 (9.0%) | 5 (8.2%) |
|
||
|
||
Stable angina, |
8 (4.2%) | 5 (8.2%) |
Unstable angina, |
18 (9.5%) | 16 (26.2%) |
ST-elevation myocardial infarction, |
58 (30.7%) | 18 (29.5%) |
Non-ST-elevation myocardial infarction, |
105 (55.6%) | 22 (36.1%) |
CAD = coronary artery disease; MI = myocardial infarction; PCI = percutaneous coronary intervention.
Lesion and procedural characteristics for the entire population (
Variables |
|
|
---|---|---|
Number of lesions ( |
217 | 66 |
|
||
|
||
Left anterior descending artery, |
105 (48.4%) | 33 (50.0%) |
Right coronary artery, |
73 (33.6%) | 22 (33.3%) |
Left circumflex artery, |
38 (17.5%) | 11 (16.7%) |
Left main, |
1 (0.5%) | 0 (0) |
|
||
|
||
Type A, |
6 (2.8%) | 4 (6.1%) |
Type B1, |
30 (13.8%) | 17 (25.8%) |
Type B2, |
108 (49.8%) | 30 (45.5%) |
Type C, |
73 (33.6%) | 15 (22.7%) |
Total occlusion, |
69 (31.8%) | 14 (21.2%) |
Total number of stents, ( |
230 | 76 |
Number of stents per patient (mean ± SD, mm) |
|
|
Number of stents per lesion (mean ± SD, mm) |
|
|
Average stent length (mean ± SD, mm) |
|
|
Average stent diameter (mean ± SD, mm) |
|
|
Predilation, |
187 (98.9%) | 59 (96.7%) |
Postdilation, |
127 (67.2%) | 34 (55.7%) |
Lesion success (%) | 100% | 100% |
Device success (%) | 100% | 100% |
Procedure success (%) | 100% | 100% |
ACC/AHA = American College of Cardiology/American Heart Association.
Results of quantitative coronary angiography analysis at preprocedure, postprocedure, and 9-month follow-up (
In-segment | In-stent | |
---|---|---|
|
||
Reference vessel diameter (mm) |
|
— |
Diameter stenosis (%) |
|
— |
Minimal lumen diameter (mm) |
|
— |
Lesion length (mm) |
|
— |
|
||
|
||
Reference vessel diameter (mm) |
|
|
Diameter stenosis (%) |
|
|
Minimal lumen diameter (mm) |
|
|
Acute gain (mm) |
|
|
|
||
|
||
Reference vessel diameter (mm) |
|
|
Diameter stenosis (%) |
|
|
Minimal lumen diameter (mm) |
|
|
Late lumen loss (mm) |
|
|
Binary restenosis (%) | 1.5 | 1.5 |
Pre- and postprocedural and 9-month QCA measurements were performed on the first 61 consecutive patients (66 lesions) who consented to a 9-month follow-up evaluation by QCA, irrespective of presence of symptoms, and are presented in Table
Cumulative frequency distribution curves of in-stent minimal lumen diameter by QCA.
The in-hospital incidence of cardiac death, MI, TLR, TVR-nontarget lesion, and/or stent thrombosis was 0%. Clinical follow-up up to 12 months was completed in all 189 patients (100%) and is summarized in Table
Cumulative clinical outcomes up to 12 months (
Variables | 30 days | 6 months | 12 months |
---|---|---|---|
Cardiac death, |
1 (0.5%) | 3 (1.6%) | 3 (1.6%) |
Noncardiac death, |
0 (0%) | 2 (1.1%) | 6 (3.2%) |
Myocardial infarction, |
1 (0.5%) | 1 (0.5%) | 3 (1.6%) |
Target lesion revascularization, |
0 (0%) | 2 (1.1%) | 4 (2.1%) |
Target vessel revascularization-non-TL, |
0 (0%) | 1 (0.5%) | 3 (1.6%) |
Stent thrombosis, |
0 (0%) | 0 (0%) | 1 (0.5%) |
Definite stent thrombosis, |
0 (0%) | 0 (0%) | 1 (0.5%) |
Target lesion failure, |
2 (1.1%) | 6 (3.2%) | 10 (5.3%) |
TL = target lesion.
Due to concern related to impaired healing and inflammation associated with first-generation durable polymer DES, scientific interest has been created in developing newer devices, with improved polymer and metallic platform technologies [
Furthermore, in clinical circumstances, thin-strut stents have been shown to produce less neointimal hyperplasia than thick-strut bare-metal stents [
In this MANIPAL-FLEX study, patient population had higher rates of hypertension (51.3%), hypercholesterolemia (32.3%), type B2/C (83.4%) lesions, and total occluded (31.8%) lesions compared to real-world Supralimus-Cores’ S-CORE registry and CORE registry [
Additionally, in-stent late lumen loss at 9-month poststent implantation was one of the secondary endpoints of the MANIPAL-FLEX study. The main aim to select this endpoint was that late lumen loss as an angiographic factor is confirmed to be a dependable predictor of the long-term clinical efficacy of DES and also strong predictor of binary restenosis and TLR [
In this study, the primary outcome, 5.3% TLF rate at 12 months, compares well to the 5.1% TLF rate reported for the Orsiro DES in the BIOFLOW-III registry [
This study is limited by the fact that it is a single-arm, nonrandomized study without comparator or adequate statistical power for conclusive definition of angiographic outcomes. In addition, limited clinical outcomes up to 12 months may not be enough to capture all the adverse events, especially very late stent thrombosis. Accordingly, these results must be measured in a comparative study with larger population, over longer follow-up duration.
This MANIPAL-FLEX study provided preliminary evidence for the feasibility, safety, and efficacy of the Supraflex SES. In this study, the Supraflex, thin-strut biodegradable polymer coated sirolimus-eluting stent demonstrated high-level efficacy, by the relatively low late lumen loss, at 9-month angiographic follow-up. Also, implantation of the Supraflex SES was proven to be safe, with high acute lesion, procedure, and device success rates. A randomized study with larger study population and over long-term follow-up is needed for further information and validation.
The authors declare that there is no conflict of interests regarding the publication of this paper.