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Cardiology Research

Original Article

Volume 14, Number 4, August 2023, pages 291-301

A Randomized Controlled Trial Comparing BioMime Sirolimus-Eluting Stent With Everolimus-Eluting Stent: Two-Year Outcomes of the meriT-V Trial

Coronary artery disease (CAD) remains a current predominant cause of mortality for the global population, irrespective of ethnicity and despite the several technological advancements. Timely intervention is key to control the rising incidence of sudden cardiac death among elderly populations susceptible to CAD [1].

Totally percutaneous, catheter-based treatment utilizing balloon angioplasty and stent implantation remains as the mainstay of management of CAD, which transformed with the introduction of drug-eluting stents (DESs). The first-generation DES designs were composed of stainless steel and had a thick strut (> 100 µm), incorporating a thick polymer coating for carrying the antiproliferative drug. In the second-generation DES designs, both the polymer coating and strut were reduced in thickness, which minimized the bulkiness of the DES structure [2]. However, the second-generation DESs commonly had a permanent polymer coating, such as a fluorinated copolymer as is present in the well-established second-generation durable polymer (DP)-based everolimus-eluting stent (EES), XIENCE (Abbott Vascular, Santa Clara, CA, USA) (Table 1). This EES has an 81-µm strut structured on a L605 cobalt-chromium alloy frame. It has a 7.6-µm non-adhesive, fluorinated copolymeric coating that releases everolimus [2]. Emerging reports showed that although the second-generation DP-DES offered better flexibility and corrosion resistance in comparison to metallic stents, reduced the incidences of cardiac death and MI, and were able to maintain the low rates of restenosis and late stent thrombosis (ST) [3], the challenges related to delayed endothelialization [4] and risk for very late ST remain [5]. In addition to the relatively high rates of target lesion revascularization (TLR) and target vessel-related myocardial infarction (TV-MI) after 1 year, the propensity for delayed endothelialization and very late stent failure remains a challenge for all existing DES designs [4, 6]. Hence, comparative investigations between DES designs are necessary to ascertain the long-term implications of implanting them in increasing CAD populations. Furthermore, the advantages of DP-based DESs in comparison to stainless steel-based first-generation DESs are established. Even the advantages of biodegradable polymer (BP)-DESs in comparison to the first-generation DESs have been established; however, the comparisons between DP-based DES and BP-DESs remain controversial [7].

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Table 1. Design Characteristics of the DES Used in the meriT-V Trial [2]

One novel BP-based DES is the BioMime sirolimus-eluting coronary stent system (Meril Life Sciences Pvt. Ltd., India), which has aroused recent research attention. This is a Conformite Europeenne (CE)-marked device having an ultrathin strut thickness (65 µm) and a proprietary co-polymer matrix (BioPoly™) consisting of biocompatible and bioabsorbable polymers: poly-L-lactic acid (PLLA) and poly-lactic-co-glycolic acid (PLGA). The polymer coating pattern of BioMime sirolimus-eluting stent (SES) is conformal [8], which degrades within 30 - 60 days after complete elution of the drug (sirolimus) that occurs within 30 days [8-11]. The stent is composed of L605 cobalt-chromium alloy, which has a higher stent density and permits the design of ultrathin struts with a higher yield strength compared to stainless steel [3, 11, 12]. This SES has a hybrid structure composed of open and closed cells that exclusively prevents side-branch jailing. The novel stent design incorporating the Nextgen™ platform reduces the likelihood of edge dissection and favors adequate stent expansion because of the unique strut width variability that ensures < 3% recoil and 0.29% foreshortening [10, 11]. Earlier, various single-arm investigations of the BioMime SES have been conducted with angiographic and clinical endpoint assessments, which demonstrated satisfactory clinical outcomes, including high procedural success and absence of major adverse cardiac events (MACEs) or ST, as evidenced in the series of meriT trials [9, 13, 14] (Table 2) and the 9-month clinical and angiographic outcomes of the meriT-V trial established that the BioMime SES is not inferior to its contemporary XIENCE EES in terms of minimizing the in-stent late lumen loss (LLL) (0.15±0.27 vs. 0.15±0.29; 95% confidence interval (CI): -0.006 (-0.09; 0.07), P = 0.87) [15].

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Table 2. Clinical Outcomes of meriT Series Trials

The long-term implications of implanting different DES devices with respect to the effect of eluting everolimus or sirolimus remain to be clarified. Moreover, the factors contributing to the reduction of the late revascularization rates remain unassorted until now [6, 16], even though there have been large clinical investigations on different BP-DESs and DP-DESs eluting paclitaxel or rapamycin analogues. In that regard, the meriT-V trial compared the novel BP-based SES with the well-established second-generation DP-based XIENCE V [15] (Table 2). Herein, we report the 2-year clinical efficacy and safety among patients with ischemic heart disease randomized and implanted with either BioMime SES or XIENCE EES systems for the treatment of coronary lesions.

The meriT-V trial was a prospective, randomized, active-controlled trial with a multicenter, open-label design. The study design and trial methodology including the randomization process have been published earlier [15]. Overall, 256 subjects underwent percutaneous coronary intervention (PCI) using the BioMime SES or the XIENCE EES with a 2:1 randomization. This report presents the data of patients who successfully completed the 2-year observation period at 15 different clinical centers in Europe and Brazil.

The intended patient population included patients with myocardial ischemia (including silent ischemia) and ischemic heart disease. In brief, the inclusion criteria were: 1) patient age ≥ 18 years, 2) patients with documented evidence of silent ischemia/angina, de novo coronary lesions, 3) lesion length ≤ 46 mm, target lesion reference vessel diameter between 2.5 and 3.5 mm, and 4) willing to attend clinical and angiographic follow-up and provide consent for the total study duration. Exclusion criteria were as follows: patients with 1) evidence of Q-wave or non-Q-wave myocardial infarction (MI) within 72 h preceding the index procedure, unless the creatine kinase (CK) and creatine kinase-myocardial band (CK-MB) enzymes are less than twice the upper limit of normal, 2) prior PCI near the target lesion (within 10 mm or at the lesion site), 3) an untreated significant lesion of > 40% diameter stenosis (DS) remaining proximal or distal to the target site after the planned intervention, 4) significant side-branch lesion (branch diameter > 2 mm) that potentially could be covered by stenting, 5) known hypersensitivity or contraindication to aspirin, heparin, clopidogrel, prasugrel, ticagrelor, sirolimus, everolimus or the contrast media, 6) left main CAD, aorto-ostial lesion, unprotected left main lesion, or a lesion within 5 mm of the origin of the left anterior descending or left circumflex, and 7) calcified target vessel or lesion [15].

This study was initiated after protocol was reviewed and approved by the local ethics committee and Institutional Review Board by the respective sites according to local regulations. The study was conducted in conformity with the protocol and as per the International Conference on Harmonization Guideline for Good Clinical Practice (ICH-GCP).

The endpoint of three-point MACEs inclusive of cardiac death, ischemia-driven target vessel revascularization (ID-TVR), and all MI was considered for the combined safety and efficacy evaluation at the 2-year landmark. Other efficacy endpoints were individually evaluated, including ischemia-driven target lesion revascularization (ID-TLR) and late ST for the population that completed the 2-year follow-up. MI was adjudicated as any MI recorded on the basis of clinical symptoms of ischemia or infarction, in association with the electrocardiographic findings and cardiac biomarker findings or pathologic evidence of infarction [17, 18]. Periprocedural MI was defined as total CK-MB elevation > 3× the upper limit of normal [17, 19]. Spontaneous MI, periprocedural MI, and TV-MI were included in the MI event records as per the first Universal Definition of MI [17, 19]. According to the 2007 Academic Research Consortium (ARC) definitions, ID-TVR was defined as a repeat PCI or coronary artery bypass grafting (CABG) of the target vessel associated with ≥ 50% diameter reduction together with documented ischemia [20]. ID-TLR was defined as revascularization by PCI or CABG associated with DS of ≥ 50% with ischaemia-related symptoms, or DS of ≥ 70% observed even without any signs and symptoms of ischemia at the time of follow-up angiography, as per the 2007 ARC definition [20]. The cases of ST were assessed based on the definitions by the 2007 ARC document [20].

The results were reported as mean ± standard deviations for continuous variables and as counts and percentages for categorical variables. The P-values were calculated using the one-sided, two sample, equal-variance t-test for continuous data and Fischer’s exact test or Pearson’s Chi-squared test for categorical data. The P-value < 0.05 was considered for statistical significance. With reference to the SPIRIT III study [21] for the XIENCE arm and the meriT-2 study for the BioMime arm, we had earlier estimated the true difference (δ) = (µT - µS) between both groups to be 0.04 mm as the mean composite endpoint rate difference at the 9-month follow-up with standard deviation (σ) of 0.41 mm for both treatment groups (0.41 mm being the highest σ for XIENCE V as per SPIRIT III study).

Since the primary endpoint was in-stent LLL that is measured per lesion, with a randomization ratio of 2:1 and a non-inferiority margin of 0.195 mm, the minimum necessary study sample size was 258 patients (control arm: 86 and study arm: 172). This sample size was deemed adequate to reach the minimum necessary sample size of 231 subjects for the efficacy evaluation. As per the post-hoc power calculation using the one-sided, two-sample, equal-variance, t-test with a significance level (α) = 0.05 (α = 0.05, β = 0.10, both one-sided) and assuming 1.2 lesions per patient, 154 patients for BioMime SES arm and 77 for XIENCE EES arm were required to achieve target 88.4% power for non-inferiority determination. Whereas, the post-hoc power calculation revealed that the meriT-V achieved 88.6% power after accounting the drop-out rates and applying the exclusion criteria; the actual arm sizes were 170 and 86 subjects.

Of the 256 patients enrolled, 98.44% patients (n = 252/256) completed the 2-year follow-up. The BioMime arm had a slightly higher cardiac risk status as the XIENCE arm, though without statistically significance. This arm included a higher proportion of patients having a previous MI (n = 37/168 patients). The total study population had a high proportion of patients with stable angina (BioMime vs. XIENCE: 68.24% vs. 70.9%, P = 0.66) (Table 3). Detailed baseline characteristics of the study population have already been published earlier [15]. For the study population that completed the 2-year follow-up, the three-point MACEs for both arms were slightly high (BioMime vs. XIENCE: 7.74% vs. 9.52%, P = 0.63) including significantly lower cumulative incidence of MI in the BioMime arm (BioMime vs. XIENCE: 1.79% vs. 5.95%; P = 0.17). This trend of non-significant differences was reflected in the incidences of ID-TVR as well, including the TLR incidence (BioMime vs. XIENCE: 5.95% vs. 3.57%; P = 0.45) (Table 4).

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Table 3. Baseline Characteristics and Medical History of the Patients in BioMime™ and XIENCE Arm [15]

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Table 4. Cumulative Clinical Outcomes of Both Study Arms Through the 2-Year Follow-Up

In the BioMime arm, definite or probable ST did not occur over the 2-year study period, while one instance (1.19%) was documented in the XIENCE arm (P = 0.16). During the entire observational period of the trial, no events of cardiac death had occurred while the ID-TVR (non-TLR) across both the study arms (2.38%; P = 0.99) were similar. The 2-year clinical outcomes have been summarized as cumulative frequencies with percentages (Table 4).

The current study is the first-ever global randomized controlled clinical trial that provided long-term follow-up data on a novel ultrathin (65 µm) strut SES having the PLLA-PLGA coating and eluting sirolimus with the lowest drug dose density (1.25 µg/mm²) [10] and the best-in-class second-generation DES, XIENCE V. Although the meriT-V trial enrolled a limited population, the outcomes data provide substantial evidence on the safety of both these devices, as minimal MACE, negligible deaths, and ST were observed until the 2-year follow-up. The cumulative MACE of the BioMime arm (7.74%) included 10 revascularizations of the target vessel including those of the non-target lesions, three MI (1.79%), and no cardiac deaths. The cumulative frequency of MI for this study device is quite low, in comparison to that reported for contemporary devices (Table 5) [22-28].

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Table 5. Clinical Outcomes of Contemporary Trials on BP-DES and DP-DES Designs

Both the stents studied have a cobalt-chromium platform and a conformal coating of polymer [8]. The different DES design characteristics (such as type of polymer, strut thickness) can affect the long-term clinical outcomes such as ID-TLR, ID-TVR, and incidence of MI. In this trial, all types of MI including spontaneous MI, periprocedural MI, and TV-MI were included in the endpoint assessments. Of the total eight MI incidences across both the arms, two were related to the target vessel (one in each arm). Whereas, the frequency of revascularizations was numerically higher in the BioMime arm (10 ID-TLR events) in comparison to the XIENCE arm (three ID-TLR events), which could be attributed to the 2:1 randomization that provided an unequally larger arm size of the BioMime arm. Hence, the current 2-year data of ID-TVR and ID-TLR have insignificant differences (BioMime vs. XIENCE = 5.95% vs. 3.57%, 95% CI: -3.86 to 8.62; P = 0.45). Furthermore, we observed that the frequency of MACE was high in the first 12 months, which slowed down considerably after the 1-year landmark. No revascularizations were recorded after 1 year following PCI for both the study arms and only two incidences of MI have occurred after 1 year. We have conducted a Kaplan-Meier analysis of the individual components of MACE except for cardiac death (Figs. 1 and 2).

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Figure 1. Kaplan-Meier analysis of ID-TVR up to the 2-year follow-up. ID-TVR: ischemia-driven target vessel revascularization.

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Figure 2. Kaplan-Meier curve of the cumulative incidence of all MI events in both study arms. MI: myocardial infarction.

Reduction in strut thickness affects the late-term clinical outcomes, including the reduction of restenosis and incidence of target lesion failure (TLF). As pointed by Bangalore et al, in their meta-analysis of 10 randomized controlled trials (RCTs) (11,658 patients) [29], the newer-generation BioMime SES, Orsiro SES, and MiStent BP-DESs (60 - 65 µm) showed a moderate reduction (16%) in the incidence of TLF compared to the thicker strut DES counterparts - Resolute Integrity, Nobori, and XIENCE (81 - 120 µm). In this meta-analysis, TLF was a composite of cardiovascular death, TV-MI, or ID-TLR and evaluated for 1-year follow-up. Furthermore, Bangalore et al noted that the low risk of TV-MI with BP-DESs contributed to the reduction in TLF [29]. Among the BP-DESs assessed in that meta-analysis, BioMime has a consistent ultrathin strut thickness (65 µm) along with MiStent (64 µm), in contrast to Orsiro SES that has a 60-µm strut for stents up to the 3.0 mm diameters and 80 µm struts for 3 to 4.5 mm diameters [22].

The newer-generation BP-DES Orsiro has shown substantial reduction in the incidence of TLF, as observed in the BIOFLOW V trial over 12 months (6%), 3 years (8.2%), and 5 years (12.3%) [23, 30, 31] (Table 5). In comparison, the 2-year MACEs of the BioMime arm in this trial seem well-consistent; however, extended follow-up studies would be necessary to ascertain the long-term outcomes. From the meta-analysis conducted by El-Hayek et al on RCTs evaluating the efficacy and safety between DP-based and BP-based DESs (16 RCTs, 19,886 patients), it is clarified that BP-DESs are superior to first-generation DP-DES designs in reducing the incidence of MI and cardiac death. Moreover, they also remarked that very few studies (six of 16) have evaluated the outcomes after the 1-year landmark. They reported that the risk for TVR was similar between BP-DES and DP-DES (risk ratio (RR): 1.12, 95% CI: 0.93 to 1.35; P = 0.25). Even the incidence of very late ST was comparable between both arms (BP-DES vs. DP-DES: 0.37% vs. 0.45%, RR: 0.87, 95% CI: 0.49 to 1.53; P = 0.62) [7]. This meta-analysis concluded that in terms of TVR, cardiac mortality, and late ST, both BP-DES and DP-DES are comparable, while the frequency of very late ST (beyond 1 year) was only slightly higher for DP-DES without statistical significance (0.98% vs. 1.15%). The authors postulated that the current generation of BP-DESs and DP-DESs have a similar safety and efficacy profile [7].

The novel sirolimus-eluting ultrathin-strut BioMime stent is a CE-marked, newer-generation device incorporating a biodegradable copolymeric matrix with favorable reports of biocompatibility and enhanced drug deliverability [31]. Its novel design with an ultrathin-strut thickness (65 µm) is aimed at reducing intra-arterial injury and improving the deliverability of sirolimus through the 2-µm BP coating that degrades within 30-60 days [9, 10, 32].

In continuation of the previously reported single-arm meriT trials that show acceptable safety and efficacy outcomes of the BioMime SES up to the 1-year follow-up (Table 4), the 9-month outcomes of meriT-V trial show the non-inferiority between both DESs in terms of LLL (0.15±0.27 vs. 0.15±0.29; 95% CI: -0.006 (-0.09; 0.07), P = 0.87) [15]. Furthermore, the cumulative MACE of 8.1% (inclusive of 2.09% cases of cardiac deaths, 1.34% cases of MI, and 0.5% ST) was reported in the Billar registry for a large study population (n = 696) comprising patients with long, diffuse lesions treated using the non-tapered BioMime SES [33].

The design of this ultrathin-strut BP-DES incorporates a L605 cobalt-chromium platform (Nextgen™), which is considered superior to the stainless steel-based metallic platforms in terms of: 1) higher yield strength, 2) better radiopaque visibility, and 3) enabling the design of ultrathin struts that is targeted at reducing ST and late restenosis [8]. Hence, we can assert that this device has potential features necessary for reducing late (> 6 months) restenosis and ST, as observed in earlier single-arm multicenter studies on this device (Table 4), where minimal ST rates were reported (0-0.4%) up to the 1-year follow-up [9, 13, 14]. Similarly, minimal ST was observed in the meriT-V trial at the completion of 2-year follow-up for both XIENCE and BioMime arms.

As reported above, the 2-year outcomes of the meriT-V trial are congruent with the outcomes reported in contemporary literature for respective DESs (Table 5). The overall outcomes of the BioMime arm suggest that the BioMime SES possesses the potential characteristics necessary for reducing the late-term incidence of ID-TVR, MI, cardiac death, and very late ST (Table 4).

Regarding the numerical differences in the incidences of all MI between both study arms, we noted that in the BioMime SES arm, one elderly patient aged 76 years had prior PCI and MI, with liver disease, chronic lung disease, renal insufficiency, peripheral vascular disease, along with traditional cardiac risk factors (dyslipidemia and hypertension). This patient experienced recurrent MI after few months of the index PCI and underwent repeat PCI. The MI incidences in this group are relatively low (1.79%). Whereas, in the XIENCE arm (5.95%), one younger, highly comorbid patient experienced two recurrent MI events, which contributed to the high MI incidence rate in the XIENCE arm. This patient had lung and renal disease, along with peripheral vascular disease and was a regular smoker. The other MI incidences recorded of the XIENCE arm were among non-smoking patients who had significant underlying systemic diseases (liver disease, anemia, lung disease, and renal insufficiency) and cardiac risk factors (hypertension, and peripheral vascular disease). These factors may have contributed to the relatively higher MI frequency in the XIENCE arm.

It is worth noting that among the 10 patients in the BioMime arm who underwent repeat revascularizations, there were commonly younger patients. Moreover, 50% of these patients had diabetes. The revascularizations were more frequent in patients with prior MI or prior PCI in this arm. In addition, four of the revascularizations were in the non-target lesion. These potentially contributory factors were notable in the BioMime arm for the slightly high ID-TVR endpoint rate.

The limitations of the trial need to be acknowledged, including the small sample size and the short length of follow-up. However, since it is a prospective study, we believe that the study results hold high clinical significance particularly for the management of the patients with stable CAD, including myocardial ischemia. We have performed a post-hoc power calculation using a one-sided, two-sample, equal-variance t-test with the actual trial drop-out rates, which revealed that the study had obtained 88.6% power. Nevertheless, we ascertain the need for further larger randomized controlled studies with both devices that have a longer duration of observation. The increasing evidence of the efficacy and clinical outcomes of BioMime SES compared with contemporary BP- and DP-based designs would further establish its efficacy among DESs.

The objective comparisons between the newer-generation DES (BioMime SES) and the conventional DP-based XIENCE EES affirm that both the devices had acceptable safety outcomes up to the 2-year follow-up. Most importantly, the frequencies of ID-TVR, ID-TLR, and MI declined considerably after the 1-year timeframe in both the arms. Hence, the study shows acceptable efficacy of the respective devices in reducing the need for repeat vascularization and late-term ST. Since this trial had a moderate sample size, further research on these devices would be necessary to ascertain the satisfactory long-term safety and efficacy for increasing CAD populations.

Acknowledgments

None to declare.

Financial Disclosure

Meril Life Sciences Pvt. Ltd., India, sponsored the meriT-V trial.

Conflict of Interest

Dr. Udita Chandra is a fulltime employee of Meril Life Sciences Pvt. Ltd., India. The other authors affirm that that the study was carried out without any commercial or financial ties that might be viewed as a potential conflict of interest.

Informed Consent

Prior to enrolment, written informed consent was obtained from all subjects randomized in the study arms.

Author Contributions

All authors conceptualized and planned the study particulars. AA, RC, SK, EK, ST, AE, OH, MM, FF-O, KM, PL, RB, AI, JK, PK, LJ recruited and conducted the trial protocol at their respective sites. UC was involved in the drafting, editing, and reviewing of the manuscript. All authors have reviewed the final manuscript and agree to take responsibility for the content of the published manuscript.

Data Availability

The authors declare that data supporting the findings of this study are available within the article.

Abbreviations

ACS: acute coronary syndrome; ARC: Academic Research Consortium; BP: biodegradable polymer; CABG: coronary artery bypass grafting; CAD: coronary artery disease; CE: Conformite Europeenne; CK: creatine kinase; CK-MB: creatine kinase-myocardial band; DES: drug-eluting stent; DP: durable polymer; DS: diameter stenosis; EES: everolimus-eluting stent; ICH-GCP: International Conference on Harmonization Guideline for Good Clinical Practice; ID-TLR: ischemia-driven target lesion revascularization; ID-TVR: ischemia-driven target vessel revascularization; LLL: late lumen loss; MACE: major adverse cardiac event; MI: myocardial infarction; PCI: percutaneous coronary intervention; PLLA: poly-L-lactic acid; PLGA: poly-lactic co-glycolic acid; RCTs: randomized controlled trials; SES: sirolimus-eluting stent; ST: stent thrombosis; TLF: target lesion failure; TLR: target lesion revascularization; TV-MI: target vessel-related myocardial infarction

1. Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, Baker-Smith CM, et al. Heart disease and stroke statistics-2023 update: a report from the American Heart Association. Circulation. 2023;147(8):e93-e621.
   doi pubmed
2. Foin N, Lee RD, Torii R, Guitierrez-Chico JL, Mattesini A, Nijjer S, Sen S, et al. Impact of stent strut design in metallic stents and biodegradable scaffolds. Int J Cardiol. 2014;177(3):800-808.
   doi pubmed
3. Xu W, Sasaki M, Niidome T. Sirolimus release from biodegradable polymers for coronary stent application: a review. Pharmaceutics. 2022;14(3):492.
   doi pubmed pmc
4. Otsuka F, Byrne RA, Yahagi K, Mori H, Ladich E, Fowler DR, Kutys R, et al. Neoatherosclerosis: overview of histopathologic findings and implications for intravascular imaging assessment. Eur Heart J. 2015;36(32):2147-2159.
   doi pubmed
5. Serruys PW, Farooq V, Kalesan B, de Vries T, Buszman P, Linke A, Ischinger T, et al. Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial. JACC Cardiovasc Interv. 2013;6(8):777-789.
   doi pubmed
6. Yeh RW, Silber S, Chen L, Chen S, Hiremath S, Neumann FJ, Qiao S, et al. 5-year safety and efficacy of resolute zotarolimus-eluting stent: the RESOLUTE global clinical trial program. JACC Cardiovasc Interv. 2017;10(3):247-254.
   doi pubmed
7. El-Hayek G, Bangalore S, Casso Dominguez A, Devireddy C, Jaber W, Kumar G, Mavromatis K, et al. Meta-Analysis of Randomized Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-Generation Durable Polymer Drug-Eluting Stents. JACC Cardiovasc Interv. 2017;10(5):462-473.
   doi pubmed
8. Thakkar AS, Dave BA. Revolution of drug-eluting coronary stents: an analysis of market leaders. EMJ. 2016;1(4):114-125.
9. Dani S, Costa RA, Joshi H, Shah J, Pandya R, Virmani R, Sheiban I, et al. First-in-human evaluation of the novel BioMime sirolimus-eluting coronary stent with bioabsorbable polymer for the treatment of single de novo lesions located in native coronary vessels - results from the meriT-1 trial. EuroIntervention. 2013;9(4):493-500.
   doi pubmed
10. Leone A, Simonetti F, Avvedimento M, Angellotti D, Immobile Molaro M, Franzone A, Esposito G, et al. Ultrathin Struts Drug-Eluting Stents: A State-of-the-Art Review. J Pers Med. 2022;12(9):1378.
    doi pubmed pmc
11. Kumar AS, Hariram V. Indigenous stents: examining the clinical data on new technologies. Interventional Cardiology. 2014;6(3):319-333.
12. Lee DH, de la Torre Hernandez JM. The newest generation of drug-eluting stents and beyond. Eur Cardiol. 2018;13(1):54-59.
    doi pubmed pmc
13. Seth A, Costa RA, Kaul U, Wander GS, Mullasari A, Nanjappa CM, Heggunje-Shetty P, et al. Late angiographic and clinical outcomes of the novel BioMime™ sirolimus-eluting coronary stent with ultra-thin cobalt-chromium platform and biodegradable polymer for the treatment of diseased coronary vessels: results from the prospective, multicentre meriT-2 clinical trial. Asia Intervention. 2016;2:19-27.
14. Jain RK, Chakravarthi P, Shetty R, Ramchandra P, Polavarapu RS, Wander GS, Mohan B, et al. One-year outcomes of a BioMime Sirolimus-Eluting Coronary Stent System with a biodegradable polymer in all-comers coronary artery disease patients: The meriT-3 study. Indian Heart J. 2016;68(5):599-603.
    doi pubmed pmc
15. Abizaid A, Kedev S, Kedhi E, Talwar S, Erglis A, Hlinomaz O, Masotti M, et al. Randomised comparison of a biodegradable polymer ultra-thin sirolimus-eluting stent versus a durable polymer everolimus-eluting stent in patients with de novo native coronary artery lesions: the meriT-V trial. EuroIntervention. 2018;14(11):e1207-e1214.
    doi pubmed
16. Natsuaki M, Morimoto T, Furukawa Y, Nakagawa Y, Kadota K, Yamaji K, Ando K, et al. Late adverse events after implantation of sirolimus-eluting stent and bare-metal stent: long-term (5-7 years) follow-up of the Coronary Revascularization Demonstrating Outcome study-Kyoto registry Cohort-2. Circ Cardiovasc Interv. 2014;7(2):168-179.
    doi pubmed
17. Thygesen K, Alpert JS, White HD, Joint ESCAAHAWHFTFftRoMI. Universal definition of myocardial infarction. Eur Heart J. 2007;28(20):2525-2538.
    doi pubmed
18. Lansky AJ, Stone GW. Periprocedural myocardial infarction: prevalence, prognosis, and prevention. Circ Cardiovasc Interv. 2010;3(6):602-610.
    doi pubmed
19. Mythili S, Malathi N. Diagnostic markers of acute myocardial infarction. Biomed Rep. 2015;3(6):743-748.
    doi pubmed pmc
20. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115(17):2344-2351.
    doi pubmed
21. Gada H, Kirtane AJ, Newman W, Sanz M, Hermiller JB, Mahaffey KW, Cutlip DE, et al. 5-year results of a randomized comparison of XIENCE V everolimus-eluting and TAXUS paclitaxel-eluting stents: final results from the SPIRIT III trial (clinical evaluation of the XIENCE V everolimus eluting coronary stent system in the treatment of patients with de novo native coronary artery lesions). JACC Cardiovasc Interv. 2013;6(12):1263-1266.
    doi pubmed
22. Pilgrim T, Muller O, Heg D, Roffi M, Kurz DJ, Moarof I, Weilenmann D, et al. Biodegradable- versus durable-polymer drug-eluting stents for STEMI: final 2-year outcomes of the BIOSTEMI trial. JACC Cardiovasc Interv. 2021;14(6):639-648.
    doi pubmed
23. Kandzari DE, Koolen JJ, Doros G, Garcia-Garcia HM, Bennett J, Roguin A, Gharib EG, et al. Ultrathin bioresorbable-polymer sirolimus-eluting stents versus thin durable-polymer everolimus-eluting stents for coronary revascularization: 3-year outcomes from the randomized BIOFLOW V trial. JACC Cardiovasc Interv. 2020;13(11):1343-1353.
    doi pubmed
24. Zbinden R, Piccolo R, Heg D, Roffi M, Kurz DJ, Muller O, Vuilliomenet A, et al. Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable-polymer everolimus-eluting stent for percutaneous coronary revascularization: 2-year results of the BIOSCIENCE trial. J Am Heart Assoc. 2016;5(3):e003255.
    doi pubmed pmc
25. Katagiri Y, Onuma Y, Lurz P, Buszman P, Piek JJ, Wykrzykowska JJ, Asano T, et al. Clinical outcomes of bioabsorbable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents: two-year follow-up of the DESSOLVE III trial. EuroIntervention. 2020;15(15):e1366-e1374.
    doi pubmed
26. Lefevre T, Haude M, Neumann FJ, Stangl K, Skurk C, Slagboom T, Sabate M, et al. Comparison of a novel biodegradable polymer sirolimus-eluting stent with a durable polymer everolimus-eluting stent: 5-year outcomes of the randomized BIOFLOW-II trial. JACC Cardiovasc Interv. 2018;11(10):995-1002.
    doi pubmed
27. Buiten RA, Ploumen EH, Zocca P, Doggen CJM, van der Heijden LC, Kok MM, Danse PW, et al. Outcomes in patients treated with thin-strut, very thin-strut, or ultrathin-strut drug-eluting stents in small coronary vessels: a prespecified analysis of the randomized BIO-RESORT trial. JAMA Cardiol. 2019;4(7):659-669.
    doi pubmed pmc
28. Buccheri S, Sarno G, Erlinge D, Renlund H, Lagerqvist B, Grimfjard P, Witt N, et al. Clinical outcomes with unselected use of an ultrathin-strut sirolimus-eluting stent: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). EuroIntervention. 2021;16(17):1413-1421.
    doi pubmed pmc
29. Bangalore S, Toklu B, Patel N, Feit F, Stone GW. Newer-generation ultrathin strut drug-eluting stents versus older second-generation thicker strut drug-eluting stents for coronary artery disease. Circulation. 2018;138(20):2216-2226.
    doi pubmed
30. Kandzari DE, Mauri L, Koolen JJ, Massaro JM, Doros G, Garcia-Garcia HM, Bennett J, et al. Ultrathin, bioresorbable polymer sirolimus-eluting stents versus thin, durable polymer everolimus-eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial. Lancet. 2017;390(10105):1843-1852.
    doi pubmed
31. Kandzari DE, Koolen JJ, Doros G, Garcia-Garcia HM, Bennett J, Roguin A, Gharib EG, et al. Ultrathin Bioresorbable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents: BIOFLOW V final 5-year outcomes. JACC Cardiovasc Interv. 2022;15(18):1852-1860.
    doi pubmed
32. Bhatt S, Gujarathi S, De Benedictis M. Innovative DES technologies from Meril. Minerva Cardioangiol. 2015;63(5):441-448.
    pubmed
33. Ribas ED, Guindo J, Santos RC, Otaegui I, Gomez JA, Suarez XC, Juan S, et al. Clinical follow-up of long nontapered sirolimus-eluting coronary stent in real-world patients with de novo lesions. The Billar registry. REC Interv Cardiol. 2022;4(1):27-32.

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