Dr. Juan F. Iglesias is a Privat Docent at the University of Geneva and an interventional cardiologist at Geneva University Hospitals. He earned his medical degree and finished his general and interventional cardiology training at Lausanne University Hospitals in Switzerland, as well as at the London Chest Hospital (Barts Health NHS Trust, London, United Kingdom) and Hammersmith Hospital in London, United Kingdom (Imperial College Healthcare NHS Trust, London, United Kingdom). He is board certified in general cardiology and interventional cardiology, with a specialty on difficult and high-risk percutaneous coronary procedures such as chronic complete occlusions, intravascular imaging, and invasive coronary physiology at Lausanne University Hospital. In this video Dr. Iglesias speaks on the Differential Effects of Newer-Generation Ultrathin-Strut Versus Thicker-Strut Drug-Eluting Stents in Chronic and Acute Coronary Syndromes.
Link to Abstract-
The researchers wanted to see if ultrathin-strut and thicker-strut drug-eluting stents (DES) had different effects in individuals with chronic (CCS) and acute (ACS) coronary syndromes.
Newest-generation ultrathin-strut DES reduce target lesion failure (TLF) compared with thicker-strut second-generation DES in patients undergoing percutaneous coronary intervention.
Randomized controlled trials comparing newer-generation ultrathin-strut (70 m) DES to thicker-strut (70 m) DES were searched in PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Patients were separated into groups depending on their clinical presentation at the start of the study (CCS versus ACS). TLF, a composite of cardiac mortality, target vessel myocardial infarction, or clinically indicated target lesion revascularization, was the primary outcome (TLR).
There were 22,766 patients in all from 16 randomized controlled studies, with 9 trials reporting TLF rates in ACS patients. At a mean follow-up of 12.2 months, patients treated with ultrathin-strut DES had a reduced risk of TLF than those treated with thicker-strut DES (risk ratio [RR]: 0.85; 95 percent CI: 0.75-0.95; P = 0.006). The difference was due to a decreased risk of clinically indicated TLR in patients treated with ultrathin-strut DES (RR: 0.75; 95 percent CI: 0.63-0.89; P 0.001). Patients with CCS and ACS had similar treatment effects (relative risk ratio: 0.97; 95 percent confidence interval: 0.73-1.31; P for interaction = 0.854). TLF risk was decreased in individuals with ST-segment elevation myocardial infarction treated with ultrathin-strut DES compared to thicker-strut DES (RR: 0.74; 95 percent CI: 0.54-0.99; P = 0.049).
In patients receiving percutaneous coronary intervention, ultrathin-strut DES minimize the risk of TLF compared to thicker-strut second-generation DES, owing to a lower risk of ischemia-driven TLR. The therapy result was consistent in both CCS and ACS patients.
For patients with chronic (CCS) or acute (ACS) coronary syndromes having percutaneous coronary intervention (PCI), newer-generation drug-eluting stents (DES) are the current standard of therapy (1). Second-generation DES' superior safety and efficacy ratings compared to bare-metal stents (2) and early-generation thick-strut DES (3) have, however, essentially plateaued in recent years, revealing the need for more technical modifications in DES designs to further improve clinical outcomes.
In comparison to second-generation thicker-strut DES, newer-generation DES incorporate ultrathin-strut stent platforms and biodegradable polymers with the potential to mitigate chronic inflammation and arterial injury, accelerate endothelialization, and reduce neointimal proliferation and thrombogenicity. These characteristics may be especially beneficial in the extremely prothrombotic and proinflammatory situation of ACS (4), which is linked to delayed vascular repair (5) and a higher risk of recurrent stent-related adverse events (6). In a large-scale meta-analysis, newer-generation ultrathin-strut DES were found to improve 1-year stent-related results when compared to current second-generation thicker-strut DES (7), although the analysis did not differentiate clinical outcomes between CCS and ACS patients. When compared to thicker-strut newer-generation DES, recent evidence suggests that ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) reduce target lesion failure (TLF) at 1-year follow-up in ACS patients with (8) and without (9) ST-segment elevation myocardial infarction (STEMI). In patients with CCS or ACS having percutaneous coronary revascularization, we conducted a study-level meta-analysis of randomized clinical trials to assess the possible differential clinical effects of newest-generation ultrathin-strut DES against thicker-strut second-generation DES.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (10) standards were followed for conducting this systematic review and meta-analysis of randomized controlled trials (RCTs). PROSPERO was used to register the protocol ( CRD42021226073).
Sources of information and search method
As of September 30, 2020, we conducted a thorough literature search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases. We concentrated on RCTs published in peer-reviewed journals. Supplementary Table 1 lists the MeSH (Medical Subject Headings) phrases utilized in the literature search. Additional qualifying research were found in the reference lists of the studies, review articles, meta-analyses, and editorials identified. There were no limits on language or sample size.
Selection of research
We looked for RCTs that compared ultrathin-strut second-generation DES to thicker-strut second-generation DES for percutaneous coronary revascularization and reported clinical outcomes. Based on a prior study, an ultrathin-strut was described as a strut thickness of less than 70 m. (7). In this study, the stent strut thickness cutoffs were used as proxies for the totality of recent innovations seen in the most modern metallic DES designs, such as iterations in stent platform geometry, polymer composition, thickness, or distribution, and antiproliferative drug composition or elution kinetics. To guarantee a uniform follow-up, only results from the landmark time point of one year were considered in this meta-analysis. Individual reports from the same experiment with various follow-up periods were not included. Due to the inherent potential of bias, observational and unpublished studies were also omitted. Three authors (S.D., M.C., and Q.C.) worked separately to conduct the literature search, review the titles and abstracts found, and choose articles for inclusion based on predetermined criteria. Consensus and arbitration by a fourth author were used to settle disagreements (J.F.I.).
Extraction of data and evaluation of the danger of bias
Three independent investigators (S.D., M.C., and Q.C.) each extracted data independently, which was then validated by a fourth investigator (J.F.I.). For each study, the following data was extracted: authors, publication year, journal, study design, recruitment period, follow-up duration, number of patients randomized, and number of patients analyzed for each outcome), patient and lesion characteristics (including age, sex, comorbidities, baseline clinical presentation, relevant angiographic and procedural data), intervention and comparator characteristics (including age, sex, comorbidities, baseline clinical presentation, relevant angiographic and procedural data), intervention and comparat (including reported outcome definitions). Three investigators (S.D., M.C., and Q.C.) reviewed the studies and evaluated the risk of bias for each one using the Cochrane Collaboration criteria (11), which include allocation sequence generation, allocation concealment, participant, personnel, and outcome assessor blinding, completeness of outcome data, and selective outcome reporting. When outcome assessors were blinded, blinding was considered complete. Because of the procedural nature of the procedures, we did not think patient or performing physician blinding was necessary. High risk of bias was assigned to studies with a high or uncertain risk of bias, while low risk of bias was assigned to the other research.
Endpoints of the research
TLF, a composite of cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularization, was the primary outcome (TLR). Individual components of the primary endpoint were included as secondary endpoints, as well as any (definite, probable, or possible) or definite/probable stent thrombosis, as defined by the Academic Research Consortium (12). The same definitions as those used in the individual trials were employed (Supplemental Table 2). MI was classified as either procedural or spontaneous (Supplemental Table 2).
Given the low-to-moderate level of heterogeneity between studies, we utilized fixed-effects models with inverse variance weighting (13) to estimate relative risk ratios (RR) and their 95 percent confidence intervals for individual trials and combined values. In addition, for completeness, we produced random-effects estimates (13). Forest plots were used to show the relative contribution of each trials to the overall summary estimate. Higgins and Thompson's I2 statistic was used to quantify heterogeneity between trials, with values of 25%, between 25% and 75%, and 75% indicating low, moderate, and high heterogeneity, respectively (14). With respect to the primary endpoint of TLF, we did subgroup analyses based on baseline clinical presentation (CCS versus ACS), DES type (ultrathin-strut versus thicker-strut DES), and kind of ultrathin-strut DES employed. Using omitting RCTs with thick-strut (120 m) second-generation DES comparators, sensitivity analyses by leave-one-out were done for each individual outcome, permitting direct comparisons between ultrathin-strut (70 m) and thin-strut (81-91 m) DES. Visual inspection of funnel plots was used to determine publication bias. R program was used to conduct the statistical analysis (R-4.0.2, R Foundation for Statistical Computing).
A total of 22,766 individuals (8,15-29) were included from 16 randomized clinical studies who had percutaneous coronary revascularization with the latest-generation ultrathin-strut DES (n = 11,875) or thicker-strut second-generation DES (n = 10,891). (Figure 1, Table 1). Supplementary Table 3 summarizes the risk of bias assessment for the trials considered. The average duration of follow-up was 12.2 1.7 months. TLF rates were available for 18,356 patients, with 10,455 (57%) having ACS (ultrathin-strut DES, n = 5,359; thicker-strut DES, n = 5,096) and 7,901 (43%) having CCS (ultrathin-strut DES, n = 4,198; thicker-strut DES, n = 3,703). Table 1 shows the baseline clinical characteristics of patients participating in separate trials. Supplementary Table 4 details the dual antiplatelet medication regimen, suggested duration, and follow-up adherence. Orsiro (Biotronik) (13 trials, n = 10,284), MiStent (Micell Technologies) (1 trial, n = 703), BioMime (Meril Life Sciences) (1 trial, n = 168), and Supraflex (Sahajanand Medical Technologies) (1 trial, n = 720) biodegradable polymer sirolimus-eluting stents were among the latest-generation ultrathin-strut DES Xience (Abbott Vascular) everolimus-eluting stents (10 trials, n = 4,357); Resolute Integrity (2 trials, n = 1,295) and Resolute Onyx (1 trial, n = 1,243) zotarolimus-eluting stents (Medtronic); Nobori (Terumo) and BioMatrix (Biosensors) biolimus-eluting stents; (Biosensors). Table 2 summarizes the key properties of the newer-generation ultrathin-strut and thicker-strut DES that were examined. The ultrathin-strut DES group had strut thickness of 60 to 65 m, while the thicker-strut DES comparison group had strut thickness of 81 to 120 m.