Abstract
Background: Safety and efficacy of newer-generation and World’s thinnest everolimus eluting stent (Evermine 50) in patients with very long and multiple lesions. Method: Total of 711 patients received >40 mm long, World’s thinnest (50 µm) Evermine 50 Everolimus eluting stent (Meril Life Sciences Pvt. Ltd., India) for various indications at LPS Institute of Cardiology, GSVM Medical College, Kanpur, UP, India between August 2017 and December 2018. Primary outcome as Device-oriented composite outcome (DOCO)- composite of cardiovascular death, target vessel myocardial infarction, and target lesion revascularization, secondary end points including peri-procedural device failure (failure of stent delivery, change of stent, edge dissection, stent fracture), target vessel failure (TVF), Global Cardiovascular End Points (GCEP)- composite of all-cause death, any MI, and any revascularization, and stent thrombosis (ST) were evaluated at 1-year follow-up. Result: Mean age was 52.7±15.9 years and majority (78.6%) were male. Indications for implantation were STEMI (n=284; 46.2%), NSTEMI (n=201; 32.8%), UA (n=78; 12.6%), and CCS (n=52; 8.4%). Total of 989 lesions were treated among 711 patients. Median length of stent per lesion was 54±14 mm. DOCO occurred in 47 (6.6%) which was contributed by target vessel MI and TLR in 23 (3.2%) and 15 (2.1%) patients respectively. GCEP was observed in 117 (16.4%) at 12-month follow-up mainly attributed by any revascularization 60 (8.4%). Stent failure was seen in 36 (5.1%) patients mainly as result of failure of assigned stent delivery (n=18; 2.5%), and edge dissection (n=15; 2.1%). Definite and probable ST were observed in 8 (1.1%) and 6 (0.8%) patients respectively. Conclusion: Evermine 50 Everolimus eluting stent is safe and effective to treat unduly long and multiple lesions.
Keywords: Ultrathin stent, device-oriented composite outcome, global cardiovascular end points, stent thrombosis, evermine 50
Introduction
In the last four decades, world of percutaneous coronary intervention (PCI) has witnessed plain only balloon angioplasty, bare metal stent, drug eluting stent (DES), and finally bioresolvable vascular scaffold but the quest for best is still going on. Bare metal stent are associated with higher rate of restenosis and repeat revascularization. These complications were reduced by drug eluting stents. Higher long-term mortality secondary to stent thrombosis was one of concern of DES [1-3]. Diffuse, calcified lesions and complex high risk interventions (CHIP) are frequently being performed now. Older generation of DES had technical issues like trackibility and deliverability as they were shorter and bulkier because of their design. Current generation of DES, because of their profile (thinner struts) and different design (biodegradable vs. biostable polymer), has reduced the risk of stent thrombosis by nearly 50% [4]. Longer lesion, smaller reference vessel diameter (RVD), and diabetes are most important determinants of adverse outcome following revascularization. The prevalence of coronary artery disease in small vessel is 30%-50% among India population [5-7]. Lesions among such patients are mostly multiple and often diffuse which sometimes requires longer and multiple stents for optimal coverage, which makes PCI not only technically challenging but also carries higher risk of adverse cardiovascular outcome as a result of repeated revascularization [8,9]. In those patients, superiority of single long stent over overlapping multiple stents is not well defined [10].
The design of a typical DES consists of a metallic platform (stainless steel, cobalt chromium etc.) of variable thickness and polymer coating (biodegradable vs. biostable) which elutes antiproliferative drugs (sirolimus, paclitaxel, everolimus, zotarolimus) to prevent lesion recurrence [11]. The durable polymer carries potential of late or very late stent thrombosis (≥ 1-year) as it acts as a nidus for chronic inflammation, delayed arterial healing and neo-atherosclerosis. These risks were subsequently mitigated by introduction of biodegradable polymer stent as they disappear after releasing the drug over a certain period of time, thereby leaving only bare metal stent-like platform [12-15]. Pooled analysis from multiple trials has shown superiority of biodegradable polymer stent over durable polymer stent [16]. As stents with thicker struts are associated with increased risk of stent thrombosis and lesion recurrence, there was a quest for stents with thinner struts. Ultrathin stents (strut thickness <70 μm) with biodegradable polymer have replaced first-generation drug-eluting stents as older generation stents were relatively thicker (struts thickness- 120 μm). Ultrathin stents are more flexible, trackable and easily deliverable across complex lesions especially in smaller vessels (2.25-2.5 mm) [17]. The present study was undertaken to assess clinical safety and efficacy of World’s thinnest (50 μm) and very Long (>40 mm) Evermone-50 Everolimus Eluting Stent (SES) in spectrum of coronary lesions among real world patients.
Material and method
Study design and participants
This was a prospective, observational study conducted among patients who received Evermine 50 (Meril Life Sciences Pvt. Ltd., India) between August 2017 and December 2018 at LPS Institute of Cardiology, GSVM Medical College, Kanpur, UP, India. Indications for implantation were- (1). Acute coronary syndrome (ACS) including ST segment elevation myocardial infarction (STEMI), non ST segment elevation myocardial infarction (NSTEMI), and unstable angina (UA) (2). Chronic coronary syndrome (CCS) refractory to guideline directed medical treatment, (3). In-stent restenosis (ISR), (4). Bifurcation lesion (true and provisional lesion based on Medina classification), and (5). Intervention of degenerated grafts following post coronary artery bypass graft surgery. Baseline demographics of patients including clinical (age, sex, clinical presentation and indication for intervention), angiographic outcome (target lesion, type and character of lesion) and procedural data (type of guiding catheter, guidewire, stent, lesion preparation) were recorded. Lesion was classified as type A, B1/B2, or C as per the American Heart Association/American College of Cardiology (AHA/ACC) criteria [18]. Cut-off for significant stenosis and reference vessel diameter were ≥70% and ≥2.25 mm respectively. Among bifurcation lesion, vessel receiving long stent (≥40 mm) was included irrespective of diameter of side branch. Procedures were performed after obtaining signed informed consent from all patients and study protocol was approved by institutional ethical committee. Major exclusion criteria were intolerance to antiplatelet agents (aspirin, clopidogrel, ticagrelor, prasugrel), heparin, and sirolimus, expected major surgery within 6-months following PCI, life expectancy <12 months, and patient having cardiogenic shock.
Device description and procedural details
Evermine 50, the world’s thinnest stent having strut thickness of 50 μm, is combination product of a device (L-605 cobalt chromium alloy as stent platform) and drug (formulation of everolimus with blend of biocompatible - biodegradable copolymer acting as drug reservoir and drug releasing platform). The polymeric matrix coating consists of 50:50 mixture of lactide (poly-L-lactic acid) and glycolide (poly-lactic-co-glycolic acid) based biodegradable polymers. It has a unique hybrid cell design because of open cells in mid segment and closed cells at edges. The minimal balloon overhang (0.5 mm) with abrupt balloon shoulder further minimizes balloon induced trauma at edges. It elutes everolimus at 1.25 μg/mm2 of stent area. The average thickness of coating is 2 μm which remains same irrespective of stent diameter. It completely elutes the drug within 7 weeks while polymer takes 10 weeks to get completely degraded. The currently available diameter and length are 2-4.5 mm and 8-48 mm respectively. The thin-strut provides low-crossing profile which translates into excellent deliverability, crossability and conformability across the lesion.
The procedures were performed either through transfemoral or transradial route following standard techniques using unfractionated heparin (70-100 U/kg) as anticoagulant. Lesion modification was done using semicompliant, noncompliant, or cutting balloon except in cases of very soft lesion (thrombus laden) where direct stenting was performed. Post dilatation was performed accordingly. Multi vessel intervention was performed during index procedure except in ACS where revascularization of only culprit artery was performed followed by other vessels within 4 weeks. All patients were pre-treated with aspirin and P2Y12 inhibitors (ticagrelor, prasugrel, or clopidogrel) and dual antiplatelet (DAPT) were continued for at least 12-months followed by aspirin alone indefinitely. Preference of antiplatelet agent was ticagrelor, followed by prasugrel and clopidogrel depending on economy and drug availability. In cases of failure of stent delivery due to various technical challenges, buddy wire with or without balloon anchoring, and rarely GuideZilla extension catheter (GEC) were used [19]. In refractory cases, different stent was chosen as per operator’s preference. Cardiac biomarkers (creatine kinase-myocardial band, troponin- I and T) were measured 24 hr before and within 8 hr following intervention to diagnose periprocedural MI. All patients were followed up clinically (history, electrocardiogram, and echocardiogram) at 1 week, and then at 1, 3, 6, 9, and 12 months period. Check angiogram was performed only if they were symptomatic or when presented with acute coronary syndrome.
Study endpoints
The primary endpoint of the study was device-oriented composite outcome (DOCO), a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization driven by ischemia (TLR) which was assessed at 12 months. Secondary endpoints included individual components of primary end point, all-cause death (cardiac and non-cardiac), any revascularization, ischemia-driven target vessel revascularization (TVR), stent thrombosis, periprocedural and spontaneous MI, and device failure (composite of failure of delivery of assigned, change of stent, edge dissection, coronary perforation and stent fracture). Global cardiovascular end point (GCEP) was defined as composite of all-cause death, any MI, and any revascularization. Stent thrombosis, periprocedural MI, and spontaneous MI were defined using criteria proposed by Academic Research Consortium (ARC) [20], World Health Organization [21], and third universal definition of MI [22] respectively. Target vessel MI was attributed to entire territory (upstream and downstream) of coronary artery having target lesion or when could not be assigned to another vessel on basis of clinical presentation, laboratory data, electrocardiogram and angiographic findings [20]. Device success was defined as successful trackibility, delivery and deployment of assigned stent at target lesion with final residual stenosis ≤ 30% following post dilatation if any.
Statistical evaluation
Statistical analyses were performed using SPSS 19.0 (SPSS Inc., Chicago, IL, USA). Baseline characteristics of patients were presented as frequencies and percentages for categorical variables and mean (SD) for continuous variables. Kaplan-Meier estimate was used to construct survival curve for time-to-event variables. For it, confidence interval on each survival proportion was calculated which led to confidence curve enclosing survival curve. 95% confidence interval (CI) was calculated after deducing value of standard error of estimate (SEE) for every death at a given time. Landmark analysis of survival was performed by using 1-year landmark after censoring patients who lost follow up at various stages.
Results
During index period, revascularization was performed in 6991 patients of whom 711 patients received Evermine 50. They were followed as per protocol and finally 665 (93.5%) of them completed the follow up at 12-months (Figure 1). Baseline characteristics of the patients are presented in Table 1. Mean age of patients was 51.4±16.6 years and majority (n=454; 72.3%) were male. Risk factor were smoking (n=228; 31.9%) either in form of ciggarette/bidi (n=120; 16.8%) or smokeless tobacco (n=108; 15.1%) [37] followed by hypertension (n=161; 22.6%) and dyslipidemia (n=157; 22.1%). Various indications for PCI were STEMI (n=318; 44.7%), NSTEMI (n=225; 31.6%), UA (n=103; 14.5%), and CCS (n=65; 9.2%). On angiogram, SVD was found in 438 (61.7%) patients where left anterior descending artery (LAD), right coronary artery (RCA) and left circumflex artery (LCx) were involved in 200 (28.1%), 151 (21.2%), and 87 (12.2%) patients respectively. Similarly, DVD and TVD were reported in 176 (24.7%) and 91 (13.6%) patients respectively.
Figure 1.
Flow chart of patients enrolled in the study with follow up over 12 months (N=711).
Table 1.
Baseline and demographic characteristics of patients (N=711)
| Characteristic | No (%) |
|---|---|
| Age (years) | 51.4±16.6 |
| Male | 454 (72.3%) |
| Female | 197 (27.7%) |
| BMI (kg/m2) | 23.8±3.6 |
| Serum creatinine (mg/dL) | 1.2±0.3 |
| CAD risk factors | |
| Hypertension | 161 (22.6%) |
| Diabetes mellitus | 136 (19.1%) |
| Smokers (Ciggerette/Bidi) | 120 (16.8%) |
| Smokeless tobacco | 108 (15.2%) |
| Family history of CAD | 34 (4.8%) |
| Dyslipidemia | 157 (22.1%) |
| Clinical Presentation | |
| STEMI | 318 (44.7%) |
| NSTEMI | 225 (31.6%) |
| UA | 103 (14.5%) |
| CCS | 65 (9.2%) |
| LVEF (%) | |
| >45% | 487 (68.5%) |
| 35-45% | 123 (17.3%) |
| <35% | 101 (14.2%) |
| Medications | |
| Aspirin | 699 (98.3%) |
| Clopidogrel | 403 (56.7%) |
| Prasugrel | 206 (28.9%) |
| Ticagrelor | 102 (14.4%) |
| Statin | 697 (98.1%) |
| Beta-blocker | 492 (69.2%) |
| ACEI/ARB | 649 (91.3%) |
| CCB | 62 (8.7%) |
| Ivabradine | 69 (9.7%) |
| Aldosterone antagonist | 99 (13.9%) |
| Angiographic severity of CAD (Target vessel location) | |
| 1. SVD | 438 (61.7%) |
| a. LAD | 200 (28.1%) |
| b. LCx | 87 (12.2%) |
| c. RCA | 151 (21.2%) |
| 2. DVD | 176 (24.7%) |
| 3. TVD | 97 (13.6%) |
Data presented as mean ± standard deviation or number (percentage). BMI-Body mass index; CAD = Coronary artery disease; DM = Diabetes mellitus; PCI-Percutaneous Coronary Intervention; STEMI-ST Segment Elevation Myocardial Infarction; NSTEMI-Non ST Segment Elevation Myocardial Infarction; UA-Unstable Angina; CCS-Chronic Coronary Syndrome; LVEF-Left ventricular ejection fraction; ACEI-Angiotensin-converting enzyme inhibitor; ARB-Angiotensin-receptor blocker; CCB-Calcium-channel blocker; SVD-Single vessel disease; LAD-Left anterior descending coronary artery; LCx-Left circumflex coronary artery; RCA-Right coronary artery; DVD-Double-vessel disease; TVD-Triple-vessel disease.
Procedural details (Table 2)
Table 2.
Procedural characteristics of patients (N=711)
| Variables | Values (No; %) |
|---|---|
| Intervention (transfemoral/Radial) | 588 (82.7%)/123 (17.3%) |
| Catheter size (6 F/7 F) | 615 (86.5%)/96 (13.5%) |
| Size of vessels | |
| a. 2.25-2.5 mm | 176 (24.7%) |
| b. 2.5-3 mm | 215 (30.2%) |
| c. 3-3.5 mm | 242 (34%) |
| d. 3.5-4 mm | 78 (11.1%) |
| TIMI flow pre procedure | |
| a. Grade 0 | 103 (14.5%) |
| b. Grade 1 | 52 (7.3%) |
| c. Grade 2 | 27 (3.8%) |
| d. Grade 3 | 529 (74.4%) |
| Number of vessels stented | |
| a. 1 | 553 (77.8 %) |
| b. 2 | 103 (14.5%) |
| c. 3 | 55 (7.7%) |
| Lesion characteristics | |
| a. At least 1 complex lesion | 638 (89.8%) |
| b. At least 1 bifurcation lesion | 30 (4.2%) |
| c. At least 1 chronic total occlusion | 93 (13.1%) |
| d. At least 1 osteo-proximal lesion | 87 (12.2%) |
| e. At least 1 calcified lesion | 33 (4.6%) |
| f. In-stent restenosis (ISR) | 17 (2.3%) |
| Stents per patient | 1.4±0.3 |
| Lesions per patient (total lesion = 998) | 1.4 |
| Number of stents used per lesion | 1.1 |
| Median Stent length per lesion (mm) | 49±0.8 |
| Stent diameter (mm) | 2.8±0.3 |
| Procedural details | |
| Lesion Modification | |
| a. Direct Stenting | 25 (3.5%) |
| b. Predilataion (semi/noncompliant balloon) | 686 (96.5%) |
| c. Cutting Balloon | 43 (6.1%) |
| Stent Delivery | |
| a. Direct (On workhorse wire alone) | 647 (93.4%) |
| b. Buddy Wire | 28 (3.9%) |
| c. GuideZilla mother-in-child system | 19 (2.6%) |
| Patients who received assigned stents only (≥40 mm) | 693 (97.4%) |
| Post-dilation | 692 (97.3%) |
| TIMI flow post procedure | |
| a. Grade 0 | 06 (0.8%) |
| b. Grade 1 | 03 (0.4%) |
| c. Grade 2 | 18 (2.5%) |
| d. Grade 3 | 688 (96.2%) |
Most of procedures were performed through transfemoral route (n=588; 82.7%). 6F guide catheter was used in 615 patients (86.5%) while rest were performed using 7F guide catheter which included CTO (n=93; 13.1%) and bifurcation lesions (n=30; 4.2%). Majority of patients underwent single-vessel PCI (n=553; 77.8%). LAD was most commonly intervened artery in 200 (28.1%) patients followed by RCA and LCx in 151 (21.2%) and 87 (12.2%) patients respectively. Total of 998 lesions were treated. Direct stenting was performed in 25 (3.5%) patients. Assisted stent delivery was performed in 47 (6.5%) patients using buddy wire (n=28; 3.9%) and GuideZilla mother-in-child system (n=19; 2.6%). The lesion belonged to LCx (n=27; 57%) and RCA (n=20; 43%) as a result of tortuosity, angulation, and shepherd crook origin. Evermine 50 was used to treat all lesions except in few side branches and in cases of device failure (n=18; 2.5%).
Clinical outcomes (Table 3)
Table 3.
Peri-procedural End Point and Clinical Events during 1-Year Follow-Up (N=711)
| Variables | Value (No; %) |
|---|---|
| Device-oriented composite outcome (DOCO) | 47 (6.6%) |
| a. Cardiac death | 09 (1.2%) |
| b. Target vessel MI | 23 (3.2%) |
| c. TLR | 15 (2.1%) |
| Device Failure (Secondary) | 36 (5.1%) |
| a. Failure of assigned stent delivery | 18 (2.5%) |
| b. Edge dissection | 15 (2.1%) |
| c. Coronary perforation | 02 (0.2%) |
| d. Stent fracture | 01 (0.1%) |
| Target Vessel Failure (TVF) | 55 (7.7%) |
| Global Cardiovascular End Point (GCEP) | 117 (16.4%) |
| All-cause death | 23 (3.2%) |
| Any MI | 34 (4.7%) |
| Any revascularization | 60 (8.4%) |
| Ischemia-driven TVR | 23 (3.2%) |
| Definite stent thrombosis | 08 (1.1%) |
| a. Acute (≤ 24 hours) | 03 (0.4%) |
| b. Subacute (>24 hours to 30 days) | 04 (0.5%) |
| c. Late (>30 days to 1 year) | 01 (0.1%) |
| Probable or possible ST | 06 (0.8 %) |
| a. Acute (≤ 24 hours) | 03 (0.4%) |
| b. Subacute (>24 hours to 30 days) | 02 (0.2%) |
| c. Late (>30 days to 1 year) | 01 (0.1%) |
MI-Myocardial infarction; TLR-Target lesion revascularization; TVF-Target vessel failure (composite of cardiac death, target vessel MI, and ischemia-driven TVR); Global Cardiovascular End Points (GCEP)-composite of all-cause death, any MI, and any revascularization; ST-Stent thrombosis; TVR-Target vessel revascularization.
The primary endpoint, DOCO, observed in 47 (6.6%) patients, was mainly attributed by target vessel MI (n=23; 3.2%) and TLR (n=15; 2.1%). GCEP was observed in 117 (16.4%) patients at 12-month follow-up mainly because of any revascularization (n=60; 8.4%) and any MI (n=34; 4.7%). Assigned stent (≥40 mm) could not be delivered to target lesions in 18 (2.9%) subjects which were finally dealt by deploying shorter and overlapping stents in 6 (0.5%) patients and different stent (Yukon Choice Sirolimus eluting stent; Translumina, Germany) in 12 (1.6%) patients. Edge dissection was observed in 15 (2.1%) patients among whom site was proximal in 4 (0.5%) patients while distal in 11 (1.5%) patients. Another stent (shorter and overlapping with previous stent) was implanted in 6 (0.8%) patients to bail out them from threatened vessel closure. Stent fracture (Grade II) was seen in one patient who was asymptomatic. Definite ST was observed in 08 (1.1%) patients while probable or possible ST was reported in 06 (0.8%) patients. Among those with definite ST, acute cases were caused by malposition of stent which was finally dealt by post dilatation using oversized non-compliant balloon. Sub-acute and late ST was responsible in three and two cases respectively which were dealt by implantation of hetero DES (Xience Prime Everolimus eluting stent; Abott Vascular, USA). Figure 2 illustrates the Kaplan-Meier survival curves of patients over 12 months period which standard error of estimate was 0.0069 with 95% CI of 0.9521-0.9792. Of all deaths, fourteen deaths were attributed to non-cardiac conditions (eg, stroke, malignancy, renal failure, sepsis, and pneumonia).
Figure 2.
Kaplan-Meier survival curve of patients over 12 months period of follow up.
Discussion
The key findings in our study were: (a) PCI using ultra long and thinnest stent “Evermine 50” resulted in acceptable level of primary end point (DOCO-6.6%) and its individual components which included cardiac death (1.2%), target vessel MI (3.2%), and ischaemia driven TLR (2.1%) along with definite ST (1.1%) at the end of 12-month. These findings were consistent with event rates reported using contemporary third generation DES such as Orsiro (6%) as reported by Kandzari [14] and Synergy SES (7.5%) as reported by Lam [23].
Ultrathin strut (50 µm) may be one of the factors behind favourable result. The unique design (thinnest strut with hybrid cell) makes it swiftly trackable and deliverable across the various lesions when compared to currently available other ultrathin stents like Orsiro (Biotronik, Bülach, Switzerland)- 60 µm, Synergy Everolimus Eluting Platinum Chromium stent (Boston Scientific, USA)- 74 µm, Firehawk (Shanghai Micro Port Medical Group, Shanghai, China)- 86 µm, Supraflex Cruise SES (Sajahanand Medical Technology, Gujarat, India)- 60 µm, and MiStent SES (MiCell Technologies, Durham, NC, USA)- 64 µm. Another distinguishing feature is its unique drug elution kinetics which has shortest presence of drug (7 weeks) and polymer (10 weeks) in the vessels [24].
Thinner struts cause minimal encroachment of vessel lumen leading to maximum in-stent luminal gain, lesser turbulence with minimum eddy current formation causing lower shear stress, lower metal density, and easy strut nesting following implantation. Lower shear stress causes less platelet activation and neointimal hyperplasia. All these factors contribute to fewer acute events in form of early stent thrombosis and in-stent restenosis in longer term as thicker struts and smaller minimum in-stent lumen diameter are known independent predictors of in-stent restenosis [25]. Furthermore, thinnest strut gives more flexibility and conformability which made the stent easily trackable and deliverable during implantation [26]. These were evident in our study as only 2.6% of patients required GuideZilla mother-in-child system to assist the delivery of stent and most of them were in left circumflex vessel which had an angulated origin.
Device success (93.6%) was comparable to current generation stents like FIREHAWK (92.4%) and Xience group (94.8%) as reported in the TARGET all-comer Trial [27] but little lower than Supraflex Cruise (99.6%) as reported in TALENT Trial [28] and Orsiro SES (97.9%), Synergy EES (98.5%) as reported in BIORESORT Trial [23]. Slightly lower rate of device success in our study was because multiple parameters (including all procedural complications) were taken into consideration to define device failure while successful delivery of stent was considered as the only parameter for device success in contemprory studies [23,27,28].
Edge dissection in our study was 1.8% which was concordant with finding from TALENT Trial where it was reported as 2.8% and 2.2% for Supraflex Cruise and XIENCE respectively [28]. This was based on angiographic criteria alone. Our finding was also consistent with results from ILUMIEN II study which was based on intravascular ultrasound (IVUS) and optical coherence tomography (OCT) among patients receiving XIENCE where incidence was 2.4% and 2.8% respectively [29]. These factors support safety and efficacy of Evermine 50 further as median length of implantation in our study was 49 mm and sizeable proportion (24.7%) of patients had vessel size ≤ 2.5 mm which are known predictors of edge dissection.
Target vessel failure in our study (7.7%) was comparable to other contemporary trials which reported it as 9.9% in FIREHAWK group while 9.6% in Xience group in TARGET all-comer trial [27]. In BIO-RESORT trial which compared thin, very thin, or ultrathin strut stents using Orsiro SES, Synergy EES and Resolute Integrity ZES, it was reported as 8.5%, 8.8%, and 10% respectively [30] while it was 5.4% in TALENT trial using Supraflex Cruise stent [28]. It was mainly driven by slightly higher target vessel MI and ischemia-driven TVR as lesion length, median stent length, and proportion of small vessel involvement were higher in our study. Another trial of ultrathin sirolimus eluting stent from South Korea as reported by Youn [31] it was much lower (3.9%) which was mainly driven by higher proportion of transradial intervention (79.1% vs. 17.3%) and lower proportion of chronic total occlusion (4.2% vs. 13.1%) when compared to our study.
Global cardiovascular end point in our study was better than FIREHAWK and Xience stent (16.4% vs. 19.3% vs. 17.8%) as shown in TARGET all-comer trial [27], but higher than 9.9% as reported in TALENT trial [28]. Our finding was also discordant with result from DESSOLVE III trial where it was reported as 13.3% using MiStent [32] and 14.3% for Orsiro SES, 14.9% for Synergy EES and 15.6% for Resolute Integrity ZES as reported in BIO-RESORT study [30]. This was mostly driven by higher rate of all deaths and all myocardial infarction because of higher co-morbidities, complex lesion, higher transfemoral intervention, and longer mean length of stent per lesion.
Stent thrombosis (both definite and probable) was little higher (1.9%) in our study compared to Orsiro SES (1.1%), Synergy EES (1.1%), and Resolute Integrity ZES (0.9%) as reported in BIO-RESORT trial, [30] MiStent (1.1%) in DESSOLVE III trial [32], Supraflex Cruise (1.5%) in TALENT trial [28], and FIREHAWK (1.7%) and Xience stent (2.1%) as shown in TARGET all-comer trial [27]. The interesting point was that most of ST was either acute or sub-acute while late events were the least in our study which makes it quite safe over long term. The possible reasons for slightly higher acute ST may be longer stent and lesser number of patients receiving potent P2Y12 inhibitor like ticagrelor and prasugrel while reasons for lower rate of late ST may be reduced long-term inflammation as biodegradable polymer minimizes polymer volume and everolimus drug concentrations in the vessel.
There was a concern regarding its safety as median length per lesion in our study was 49±8 mm. Full lesion coverage with longer stent is essential to prevent in-stent restenosis (at edges) which often requires more than one stent, sometime resulting into full metal jacketing (>60 mm) [33]. In a study of 1,107 consecutive patients involving CTO procedures as reported by Lee [34], 406 (36.7%) patients underwent FMJ using overlapping stent. In their study, median length was 76.8±14.6 mm (range: 60-122 mm) which was higher than our study but DOCO was almost similar to our study (6.6% vs. 6.1%).
In India, cardiovascular diseases accounts for one quarter of deaths between 30 yrs to 70-years of population group [35]. Here, nearly half of patients have to bear their medical expenses as an organised insurance system is absent. In lieu of skyrocketing cost of multivessel PCI, many young patients opt for coronary artery bypass surgery because of economic restraint [36]. Recently, the government has drastically braught down the price of stents which carries a capping and with availability of ultra long stent (≥40 mm), cost of multivessel intervention has come down so that a lot more patients can achieve complete revascularisation. Our study also sheds important light regarding safety with ultrathin and ultra long stent in long lesion among Indian population where diffuse vessel disease is not so infrequent.
Limitation
Our study was observational study of not a large population. Moreover, disease of left main coronary artery was not included. Patients with cardiogenic shock were not included. Strut coverage and healing score was not studied using optical coherence tomography. Long term follow up (>5 years) would have provided safety data further.
Conclusion
The findings of the present study provide safety and efficacy of very long (>40 mm), and world’s thinnest DES (Evermine 50) which is a bioresorbable polymer, sirolimus eluting stent across all substrate of lesion of coronary artery. It also included full metal jacketing especially in patients with chronic total occlusion and also non-CTO diffusely diseased small vessels as well.
Disclosure of conflict of interest
None.
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