Temporal Trends in the Outcomes of Percutaneous Coronary Intervention With Zotarolimus Eluting Stents Versus Everolimus Eluting Stents: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Long-term follow-up results of various trials comparing Zotarolimus eluting stents (ZES) with Everolimus eluting stents (EES) have been published recently. Additionally, over the last decade, there have been new trials comparing the ZES with various commercially available EES. We aim to conduct an updated meta-analysis in light of new evidence from randomized controlled trials (RCTs) to provide comprehensive evidence regarding the temporal trends in the clinical outcomes. METHODS: A comprehensive literature search was conducted across PubMed, Cochrane, and Embase. RCTs comparing ZES with EES for short (<2 years), intermediate (2-3 years), and long-term follow-ups (3-5 years) were included. Relative risk was used to pool the dichotomous outcomes using the random effects model employing the inverse variance method. All statistical analysis was conducted using Revman 5.4. RESULTS: A total of 18 studies reporting data at different follow-ups for nine trials (n = 14319) were included. At short-term follow-up (<2 years), there were no significant differences between the two types of stents (all-cause death, cardiac death, Major adverse cardiovascular events (MACE), target vessel myocardial infarction, definite or probable stent thrombosis or safety outcomes (target vessel revascularization, target lesion revascularization, target vessel failure, target lesion failure). At intermediate follow-up (2-3 years), EES was superior to ZES for reducing target lesion revascularization (RR = 1.28, 95% CI = 1.05-1.58, p < 0.05). At long-term follow-up (3-5 years), there were no significant differences between the two groups for any of the pooled outcomes (p > 0.05). CONCLUSION: ZES and EES have similar safety and efficacy at short, intermediate, and long-term follow-ups.

Structural Identification of Zotarolimus (ABT-578) Metabolites Generated by Human Liver Microsomes Using Ion-Trap and High-Resolution Time-of-Flight Mass Spectrometry in Combination with the Analysis of Fragmentation Patterns.

Zotarolimus (ABT-578) is a sirolimus derivative that, like sirolimus and everolimus, is an inhibitor of cell growth via inhibition of the mechanistic target of rapamycin (mTOR). Zotarolimus was developed for coating coronary stents to prevent smooth muscle cell proliferation and restenosis. Albeit zotarolimus-eluting cardiovascular devices have been on the market for years, details of zotarolimus drug metabolism in humans are still unknown. Hence, it was the goal of the present study to identify zotarolimus metabolites generated by incubation with human liver microsomes. Metabolite structures were identified using high-resolution mass spectrometry, MS/ion-trap (MSn), and comparison of fragmentation patterns of the metabolites with those of zotarolimus and other known sirolimus derivatives. Kinetic parameters such as incubation time, human liver microsomal protein concentrations, and drug concentrations were optimized before scaling up the metabolism experiments. Human liver microsomes mainly hydroxylated and/or demethylated zotarolimus. The structures of the following metabolites were identified: O-demethylated metabolites: 39-O-desmethyl, 16-O-desmethyl, and 27-O-desmethyl zotarolimus; hydroxylated metabolites: hydroxy piperidine zotarolimus, 11-hydroxy, 12-hydroxy, 14-hydroxy, 23-hydroxy, 24-hydroxy, 25-hydroxy, 45/46-hydroxy, and 49-hydroxy zotarolimus; demethylated-hydroxylated metabolites: 16-O-desmethyl, 23/24-hydroxy; 39-O-desmethyl, 23/24-hydroxy; 39-O-desmethyl, 25-hydroxy zotarolimus; 39-O-desmethyl, 11-hydroxy zotarolimus; 39-O-desmethyl, hydroxy-piperidine zotarolimus; 27-O-desmethyl, 45/46-hydroxy zotarolimus; didemethylated metabolites: 16,39-O-didesmethyl zotarolimus; 16,27-O-didesmethyl zotarolimus; 27,39-O-didesmethyl zotarolimus; and dihydroxylated metabolites: 11,24-dihydroxy zotarolimus, 12,24-dihydroxy zotarolimus, and 11,47/48-dihydroxy zotarolimus. It is concluded that zotarolimus is extensively metabolized by human liver microsomes. Twenty-four of these metabolites could be structurally identified using a combination of ion-trap MSn and high-resolution mass spectrometry.

Stent expansion in calcified coronary chronic total occlusions: The impact of different stent platforms.

OBJECTIVES: To evaluate the stent expansion of the durable-polymer Zotarolimus-eluting stent (dp-ZES), the durable-polymer Everolimus-eluting stent (dp-EES), and the bioabsorbable-polymer Sirolimus-eluting stent (bp-SES) in calcified coronary chronic total occlusions (CTO). BACKGROUND: The newer generation stents with ultrathin struts might raise concerns regarding reduced radial strength and higher stent recoil (SR) when implanted in calcified CTOs. METHODS: Between January 2017 and June 2021 consecutive patients with CTO undergoing percutaneous coronary intervention with dp-ZES, dp-EES, or bp-SES were evaluated. The analysis was performed in calcific and in noncalcific CTOs. Quantitative coronary angiography analysis was used to assess diameter stenosis (DS), absolute and relative SR, absolute and relative focal SR, absolute and relative balloon deficit (BD), and absolute and relative focal BD. The primary endpoint was DS. RESULTS: A total of 213 CTOs were evaluated, 115 calcific CTOs (dp-ZES:25, dp-EES:29, bp-SES:61) and 98 non-calcific CTOs (dp-ZES:41, dp-EES:11, bp-SES:46). In calcific CTOs, residual DS was lower in dp-ZES than in dp-EES and bp-SES (-1.00% [-6.50-6.50] vs. 13.00% [7.0-19.00] vs. 15.00% [5.00-20.00]; p < 0.001). Dp-ZES was also an independent predictor of residual DS ≤ 10% (OR 11.34, 95% CI 2.6-49.43, p = 0.001). Absolute and relative focal SR and absolute and relative SR were similar between dp-ZES, dp-EES, and bp-SES (p = 0.913, p = 0.890, p = 0.518, p = 0.426, respectively). In noncalcified CTOs, the residual DS was similar in the three groups (p = 0.340). High relative focal SR was less frequent in dp-ZES than in dp-EES and in bp-SES (19.5% vs. 54.5% vs. 37.0%; p < 0.048). CONCLUSIONS: The three stent platforms demonstrated an overall low residual DS when implanted in CTOs. However, dp-ZES was associated with the lowest residual DS and identified as independent predictor of residual DS ≤ 10% in patients with calcific CTOs. Dp-ZES was associated with a lower incidence of high relative focal stent recoil, in noncalcific CTOs. Balloon deficit might be considerate as a surrogate for stent expansion in calcified CTOs.

A technology evaluation of the Onyx Frontier drug-eluting stent.

INTRODUCTION: Onyx FrontierTM represents the latest iteration within the family of zotarolimus-eluting stents (ZES), designed for the treatment of coronary artery disease. Approval by the Food and Drug Administration was granted in May 2022, and Conformité Européenne marking followed in August 2022. AREAS COVERED: We hereby review the principal design features of Onyx Frontier, highlighting differences and similarities with other currently available drug-eluting stents. In addition, we focus on the refinements of this newest platform as compared with previous ZES versions, including the attributes yielding its exceptional crossing profile and deliverability. The clinical implications related to both its newest and inherited characteristics will be discussed. EXPERT OPINION: The nuances of the latest Onyx Frontier, together with the continuous refinement previously witnessed throughout the development of ZES, lead to a latest generation device ideal for a diverse spectrum of clinical and anatomical scenarios. In particular, its peculiarities will be of benefit in the settings often offered by a progressively aging population, such as high bleeding risk patients and complex coronary lesions.

Comparison of long-term clinical outcomes among zotarolimus-, everolimus-, and biolimus-eluting stents in acute myocardial infarction patients with renal impairment.

BACKGROUND: It is important to determine the best drug-eluting stent (DES) for acute myocardial infarction (AMI) in patients with renal impairment. In this studythe outcomes of everolimus-eluting stents (EESs), zotarolimus-eluting stents (ZESs) and biolimus-eluting stents (BESs) were evaluated. METHODS: From the Korea Acute Myocardial Infarction-National Institutes of Health registry, a total of 1,470 AMI patients with renal impairment undergoing percutaneous coronary intervention (PCI) were enrolled (816 with EES, 345 with ZES, and 309 with BES). Renal impairment was defined as creatinine clearance < 60 mL/min/1.73 m² estimated by the Cockcroft-Gault method. Major adverse cardiac and cerebrovascular events were determined as the composite of all-cause death, non-fatal myocardial infarction (MI), cerebrovascular accident, any revascularization, rehospitalization and stent thrombosis. All clinical outcomes were analyzed. RESULTS: The baseline characteristics of the patients revealed no significant difference between the three groups, except for Killip classification > 2, beta-blockers, lesion type, vascular approach, staged PCI, left main coronary artery (LMCA) complex lesions, LMCA PCI, and the number and length of implanted stents. In the Kaplan-Meier analysis, similar clinical outcomes were derived from the unadjusted data between the three DES groups. However, after the inverse probability of treatment weighting, a statistically significant difference was found in non-fatal MI, which implied a higher incidence of non-fatal MI in the ZES group than in the other two DES groups. CONCLUSIONS: In AMI patients with renal impairment, there was no significant difference between the three stent groups in terms of long-term clinical outcomes, except for non-fatal MI.

One-year outcomes of polymer-free amphilimus-eluting stents versus durable polymer zotarolimus-eluting stents in patients with diabetes mellitus: a meta-analysis.

BACKGROUND: Diabetes mellitus (DM) and cardiovascular diseases often co-exist. Today, percutaneous coronary intervention (PCI) is the preferred revascularization procedure for majority of patients with coronary artery disease. Polymer-free amphilimus-eluting stents (AES) represent a novel elution technology in the current era of drug-eluting stents. In this analysis, we aimed to systematically compare the cardiovascular outcomes which are associated with polymer-free amphilimus-eluting stents (AES) versus the durable polymer zotarolimus-eluting stents (ZES) for the treatment of patients with DM. METHODS: Http://www. CLINICALTRIALS: gov, EMBASE, Web of Science, MEDLINE, Cochrane database and Google Scholar were searched for publications comparing polymer-free AES versus durable polymer ZES in patients with DM. Selective cardiovascular outcomes were assessed. Statistical analysis was carried out by the latest version of the RevMan software. Risk ratio (RR) with 95% confidence interval (CI) was used to represent the data analysis. RESULTS: Four studies with a total number of 1795 participants with DM whereby 912 patients were assigned to be revascularized by the polymer-free AES and 883 patients were assigned to be revascularized by the durable polymer ZES were included in this analysis. In patients with DM, at one year, polymer-free AES were associated with significantly lower risk of major adverse cardiac events (MACEs) (RR: 0.69, 95% CI: 0.54-0.88; P = 0.002) and target lesion failure (TLF) (RR: 0.66, 95% CI: 0.48-0.91; P = 0.01) compared to durable polymer ZES. However, there was no significant change in all-cause mortality (RR: 0.79, 95% CI: 0.51-1.22; P = 0.28), cardiac death and the other cardiovascular outcomes. Similar risk of total stent thrombosis (RR: 1.13, 95% CI: 0.60-2.13; P = 0.70), including definite stent thrombosis (RR: 1.12, 95% CI: 0.38-3.31; P = 0.84), probable stent thrombosis (RR: 0.87, 95% CI: 0.37-2.09; P = 0.76), possible stent thrombosis (RR: 1.19, 95% CI: 0.50-2.87; P = 0.69) and late stent thrombosis (RR: 1.00, 95% CI: 0.17-5.72; P = 1.00) as between polymer-free AES and durable polymer ZES in patients with DM. CONCLUSIONS: At 1 year follow-up, polymer-free AES were associated with significantly lower MACEs and TLF compared to durable polymer ZES in these patients with DM, without any increase in mortality, stent thrombosis and other cardiovascular outcomes. However, this analysis is only based on a follow-up time period of one year, therefore, future research should focus on the long term follow-up time period.

Airway local endoscopic pharmacological treatment; current applications and future concepts.

INTRODUCTION: Local treatment of the airways and lung parenchyma has been used in clinical practice for several years for a variety of diseases. METHODS: A variety of endoscopic tools for local treatment exist, especially for treating malignancies. Using these endoscopic tools, one can administer drugs specifically designed for the airways. DISCUSSION: This article presents all locally administered treatment options and provides useful insights for future local endoscopically applied treatments.

Polymer-Free Biolimus-Eluting Stents or Polymer-Based Zotarolimus-Eluting Stents for Coronary Bifurcation Lesions.

BACKGROUND: A polymer-free biolimus-eluting stent (PF-BES) and a zotarolimus-eluting stent (ZES) recently showed similar clinical profiles and appear to be competing options in specific clinical settings of patients undergoing percutaneous coronary intervention (PCI). Whether they perform similarly also in complex procedural settings as coronary bifurcation lesions remains unaddressed. METHODS: All consecutive patients undergoing coronary bifurcation PCI with PF-BES or the new iteration of the ZES from three large multicenter real-world registries were included. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis (ST). Multiple analyses to adjust for baseline differences were carried out including propensity-score matching, propensity-score stratification and inverse-probability-weighting. Outcomes are reported according to Cox proportional hazard models censored at 400-day follow-up. RESULTS: 1169 patients treated with PF-BES (n = 440) or ZES (n = 729) on the main branch of a coronary bifurcation lesion were included (mean age 69 ± 11 years, 75.4% male, 53.8% acute coronary syndrome at presentation, 26.6% left main bifurcation, median dual antiplatelet therapy duration 12 [range 12-12] months). MACE, all-cause death, TLR and ST tended towards non-statistically higher rates with the PF-BES as compared to the ZES. Higher MI and target vessel revascularization occurrence was observed with PF-BES. CONCLUSIONS: In this large contemporary cohort of patients undergoing coronary bifurcation PCI, the occurrence of MACE was non-statistically different with the use of PF-BES and ZES devices. However, differences favoring the ZES device that may entail clinical relevance were observed. Further studies are needed to confirm these findings and explore whether they remain valid when a short dual antiplatelet therapy is adopted.

Anti-Cancer Effects of Zotarolimus Combined with 5-Fluorouracil Treatment in HCT-116 Colorectal Cancer-Bearing BALB/c Nude Mice.

Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1ß, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor ß (TGF-ß), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.

Ten-year clinical outcomes of polymer-free versus durable polymer new-generation drug-eluting stent in patients with coronary artery disease with and without diabetes mellitus : Results of the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol- and Zotarolimus-Eluting Stents (ISAR-TEST 5) trial.

BACKGROUND: Very long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus. METHODS: We investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years. RESULTS: This analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73-1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88-1.11; P = 0.88). CONCLUSION: At 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533 Kaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons).

Five-Year Comparative Efficacy of Everolimus-Eluting vs. Resolute Zotarolimus-Eluting Stents in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Among drug-eluting stents (DESs), the durable polymer everolimus-eluting stent (EES) and resolute zotarolimus-eluting stent (R-ZES) are widely used in clinical practice and have contributed to improve the outcomes of patients undergoing percutaneous coronary intervention (PCI). Few studies addressed their long-term comparative performance in patients with acute coronary syndrome (ACS). We aimed to investigate the 5 year comparative efficacy of EES and R-ZES in ACS. We queried ACTION-ACS, a large-scale database of ACS patients undergoing PCI. The treatment groups were analyzed using propensity score matching. The primary endpoint was a composite of mortality, myocardial infarction (MI), stroke, repeat PCI, and definite or probable stent thrombosis, which was addressed at the five-year follow-up. A total of 3497 matched patients were analyzed. Compared with R-ZES, a significant reduction in the primary endpoint at 5 years was observed in patients treated with EES (hazard ratio (HR) [95%CI] = 0.62 [0.54-0.71], p < 0.001). By landmark analysis, differences between the two devices emerged after the first year and were maintained thereafter. The individual endpoints of mortality (HR [95%CI] = 0.70 [0.58-0.84], p < 0.01), MI (HR [95%CI] = 0.55 [0.42-0.74], p < 0.001), and repeat PCI (HR [95%CI] = 0.65 [0.53-0.73], p < 0.001) were all significantly lower in the EES-treated patients. Stroke risk did not differ between EES and R-ZES. In ACS, a greater long-term clinical efficacy with EES vs. R-ZES was observed. This difference became significant after the first year of the ACS episode and persisted thereafter.

The Anti-Cancer Effects of a Zotarolimus and 5-Fluorouracil Combination Treatment on A549 Cell-Derived Tumors in BALB/c Nude Mice.

Zotarolimus is a semi-synthetic derivative of rapamycin and a novel immunosuppressive agent used to prevent graft rejection. The pharmacological pathway of zotarolimus restricts the kinase activity of the mammalian target of rapamycin (mTOR), which potentially leads to reductions in cell division, cell growth, cell proliferation, and inflammation. These pathways have a critical influence on tumorigenesis. This study aims to examine the anti-tumor effect of zotarolimus or zotarolimus combined with 5-fluorouracil (5-FU) on A549 human lung adenocarcinoma cell line implanted in BALB/c nude mice by estimating tumor growth, apoptosis expression, inflammation, and metastasis. We established A549 xenografts in nude mice, following which we randomly divided the mice into four groups: control, 5-FU (100 mg/kg/week), zotarolimus (2 mg/kg/day), and zotarolimus combined with 5-FU. Compared the results with those for control mice, we found that mice treated with zotarolimus or zotarolimus combined with 5-FU retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; decreased inflammation cytokines levels (e.g., IL-1ß, TNF-α, and IL-6); reduced inflammation-related factors such as cyclooxygenase-2 (COX-2) protein and nuclear factor-κB (NF-κB) mRNA; enhanced anti-inflammation-related factors including IL-10 and inhibitor of NF-κB kinase α (IκBα) mRNA; and inhibited metastasis-related factors such as transforming growth factor ß (TGF-ß), CD44, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). Notably, mice treated with zotarolimus combined with 5-FU had significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with the groups of mice treated with 5-FU or zotarolimus alone. The in vivo study confirmed that zotarolimus or zotarolimus combined with 5-FU could retard lung adenocarcinoma growth and inhibit tumorigenesis. Zotarolimus and 5-FU were found to have an obvious synergistic tumor-inhibiting effect on lung adenocarcinoma. Therefore, both zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents for treatment of human lung adenocarcinoma.

Clinical Impact of Lesion Complexity on 2-Year Outcomes After Zotarolimus-Eluting Stents Implantation.

Background: The clinical efficacy and safety of second-generation drug-eluting stents in complex percutaneous coronary interventions (PCIs) are not well established. Objectives: The clinical influence of the lesion complexity after PCI with zotarolimus-eluting stents (ZES) was evaluated. Methods: From a prospective multicenter observational study, a total of 926 patients that underwent successful PCIs with ZES were included. Complex PCIs were defined as patients with ≥3 lesions treated, 3 vessels treated, severe calcified lesions, bifurcated lesions with 2 stents implanted, left main disease, chronic total occlusion lesions, and/or diffuse long (total stent length ≥60 mm) lesions and were compared to the noncomplex group. The primary outcome was incidence of target lesion failures at 2 years, defined as a composite of cardiac death, target lesion-myocardial infarctions, and target lesion revascularization. Results: The patients were divided into complex PCI (n = 249) and noncomplex (n = 677) groups. In the complex PCI group, the 2-year risk of a target lesion failure was not significantly higher than in the noncomplex PCI group (4.8% vs 3.7%; adjusted hazard ratio: 1.373; 95% confidence interval: 0.689-2.738; P = 0.367). The same trend was observed for all composites of the clinical outcomes. Older age and advanced chronic kidney disease were independent predictors for the primary outcome. Conclusions: Up to 2 years after a ZES implantation, the clinical outcomes did not differ according to lesion complexity.

Stent-Related Adverse Events as Related to Dual Antiplatelet Therapy in First- vs Second-Generation Drug-Eluting Stents.

Background: There are limited data on the long-term stent-related adverse events as related to the duration of dual antiplatelet therapy (DAPT) in second-generation (G2) drug-eluting stents (DES) compared with first-generation (G1) DES. Objectives: This study sought to compare the long-term stent-related outcomes of G2-DES with those of G1-DES. Methods: The study group consisted of 15,009 patients who underwent their first coronary revascularization with DES from the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) Registry Cohort-2 (first-generation drug-eluting stent [G1-DES] period; n = 5,382) and Cohort-3 (second-generation drug eluting stent [G2-DES] period; n = 9,627). The primary outcome measures were definite stent thrombosis (ST) and target vessel revascularization (TVR). Results: The cumulative 5-year incidences of definite ST and TVR were significantly lower in the G2-DES group than in the G1-DES group (0.7% vs 1.4%; P < 0.001; and 16.2% vs 22.1%; P < 0.001, respectively). The lower adjusted risk of G2-DES relative to G1-DES for definite ST and TVR remained significant (HR: 0.53; 95% CI: 0.37-0.76; P < 0.001; and HR: 0.74; 95% CI: 0.68-0.81; P < 0.001, respectively). In the landmark analysis that was based on the DAPT status at 1 year, the lower adjusted risk of on-DAPT status relative to off-DAPT was significant for definite ST beyond 1 year in the G1-DES stratum (HR: 0.42; 95% CI: 0.24-0.76; P = 0.004) but not in the G2-DES stratum (HR: 0.66; 95% CI: 0.26-1.68; P = 0.38) (P interaction = 0.14). Conclusions: G2-DES compared with G1-DES were associated with a significantly lower risk for stent-related adverse events, including definite ST and TVR. DAPT beyond 1 year was associated with a significantly lower risk for very late ST of G1-DES but not for that of G2-DES.

[Effect of the type of a coronary stent on dynamics of quality of life in patients with ischaemic heart disease]. / Vliianie vida koronarnogo stenta na dinamiku kachestva zhizni u patsientov s ishemicheskoi bolezn'iu serdtsa.

The purpose of the present study was to investigate the dynamics of quality of life in patients with ischaemic heart disease before and after implantation of a coronary stent depending on the stent's type and patient's gender. The authors analysed the dynamics of quality of life in a total of 120 patients with ischaemic heart disease. The patients were subdivided into two equal groups of 60 each. Group One patients were subjected to implantation of bare-metal stents, whereas Group Two patients received stents coated with zotarolimus as an antiproliferative agent. The control group was composed of 60 people who did not suffer from ischaemic heart disease and were comparable by the age and gender. Quality of life was investigated prior to stent implantation and 6, 12 and 24 months thereafter with the use of the SF-36 questionnaire. It was determined that the indices of quality of life before stenting of coronary arteries was higher in men than in women. However, no gender-related differences were revealed after stent implantation. The dynamics of the parameters of quality of life of patients following implantation of uncoated metal stents within 6 months turned out to have a positive and then rapidly progressing negative course, whereas implantation of stents coated with antiproliferative drug zotarolimus was within 12 months followed and accompanied by a positive and then slowly progressing negative course.

Abbreviated Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in High Bleeding Risk Patients: LEADERS-FREE and ONYX ONE.

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) has been the focus of much discussion. The risk of late stent thrombosis appears less with newer-generation stents, and polymer-free drug-coated stents (DCS) may improve clinical efficacy relative to a bare metal stent without the potential long-term hazards associated with a durable polymer. Based on the outcomes of recent clinical trials, risk stratification to identify high bleeding risk patients and appropriate selection of a polymer-free drug-coated or durable-polymer zotarolimus-eluting stent may optimize clinical outcomes in patients who require an abbreviated DAPT regimen.

Comparison of Durable-Polymer- and Biodegradable-Polymer-Based Newer-Generation Drug-Eluting Stents in Patients with Acute Myocardial Infarction and Prediabetes After Successful Percutaneous Coronary Intervention.

Hyperglycemia is an important risk factor for poor clinical outcomes in patients with acute myocardial infarction (AMI). The relative superiority of the long-term clinical outcomes of durable-polymer (DP) -based and biodegradable-polymer (BP) -based newer-generation drug-eluting stents (DESs) after successful percutaneous coronary intervention (PCI) in patients with AMI and prediabetes is not well established. We compared the clinical outcomes in such patients between DP-based and BP-based newer-generation DESs.A total of 4,377 patients with AMI and prediabetes were divided into the following two groups: the DP-DES group (n = 3,775; zotarolimus-eluting stents [ZES; n = 1,546] and everolimus-eluting stents [EES; n = 2,229]) and the BP-DES group (n = 602; biolimus-eluting stents [BES]). The primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as all-cause death, recurrent myocardial infarction (re-MI), or any repeat revascularization. The secondary endpoint was the occurrence of stent thrombosis (ST).The 2-year adjusted hazard ratio (aHR) of MACEs for ZES versus EES, ZES versus BES, EES versus BES, and ZES/EES versus BES (aHR: 1.125; 95% confidence interval [CI], 0.834-1.518; P = 0.440) were similar. The cumulative incidence of ST was also comparable between the DP-DES and BP-DES groups (aHR: 1.407; 95% CI, 0.476-4.158; P = 0.537). Moreover, the 2-year aHRs of all-cause death, CD, re-MI, target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR were similar.Patients with AMI and prediabetes who received DP-DES or BP-DES during PCI showed comparable safety and efficacy during the 2-year follow-up period.

10-Year Outcomes From a Randomized Trial of Polymer-Free Versus Durable Polymer Drug-Eluting Coronary Stents.

BACKGROUND: Outcome data after extended long-term follow-up of patients with coronary artery disease treated with drug-eluting stents (DES) in randomized clinical trials are scant. OBJECTIVES: Performance differences among devices may be expected to emerge over time depending on whether stenting is done with polymer-free or durable polymer DES. This study assessed the 10-year outcomes of patients enrolled in the ISAR-TEST-5 (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents) trial. METHODS: A total of 3,002 patients were randomized to treatment with either polymer-free sirolimus- and probucol-eluting stents (n = 2,002) or durable polymer zotarolimus-eluting stents (n = 1,000). The primary endpoint was the composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization (a device-oriented composite endpoint [DOCE]). Additional endpoints of interest were the patient-oriented composite endpoint (POCE), including all-cause death, any myocardial infarction, or any revascularization; individual components of the composite endpoints; and definite or probable stent thrombosis. RESULTS: The median age of the patients at randomization was 67.8 years. At 10 years, 63.9% of patients were alive. The rates of DOCE and POCE were high in both groups with no difference in the incidence between polymer-free sirolimus- and probucol-eluting stents and durable polymer zotarolimus-eluting stents (DOCE: 43.8% vs. 43.0%, respectively; hazard ratio: 1.01; 95% confidence interval [CI]: 0.89 to 1.14; p = 0.90; POCE: 66.2% vs. 67.7%, respectively; hazard ratio: 0.94; 95% CI: 0.86 to 1.04; p = 0.22). The rates of the individual components of the composite endpoints were comparable in both groups. The incidence of definite/probable stent thrombosis over 10 years was low and comparable in both groups (1.6% vs. 1.9%; hazard ratio: 0.85; 95% CI: 0.46 to 1.54; p = 0.58). CONCLUSIONS: At 10 years, there were no measurable differences in outcomes between patients treated with polymer-free versus durable polymer DES. The incidence of stent thrombosis was low and comparable in both groups. High overall adverse clinical event rates were observed during extended follow-up. (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents [ISAR-TEST-5]; NCT00598533).