Therapeutic Advances in Cardiovascular Disease最新文献

Background and objectives: This study quantified the 'distance to LDL-C goal' in patients at very high cardiovascular risk with uncontrolled hyperlipidaemia. 'Distance to LDL-C goal' was defined as the percentage by which low-density lipoprotein cholesterol (LDL-C) levels needed to be reduced to achieve the LDL-C goals specified in the 2016 or 2019 European Society of Cardiology/European Atherosclerosis Society guidelines.

Design and methods: This retrospective analysis using data from the IQVIA Disease Analyzer database included patients who were predominantly treated by a primary care physician, diabetologist or cardiologist between 2014 and 2018, with a diagnosis of hyperlipidaemia and an initial LDL-C measurement (index event) and one or more cardiovascular risk factors. The primary outcome was to assess the proportion of patients with uncontrolled hyperlipidaemia and to classify the 'distance to LDL-C goal' in these patients.

Results: Data from 32,963 patients were analysed (n = 27,159, n = 3873 and n = 1931 patients in the primary care physician, diabetology and cardiology cohorts, respectively). Most patients had uncontrolled LDL-C levels (⩾70 mg/dL; ⩾1.8 mmol/L) at index (91.0%, 86.4% and 94.0% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). Analysis of the 'distance to LDL-C goal' indicated that approximately one-third of patients in each cohort required an LDL-C level reduction of up to 50% relative to index to achieve their LDL-C goal (35.8%, 43.7% and 28.4% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). LDL-C control was not achieved at 36 months post-index in most patients with uncontrolled LDL-C levels (86.8%, 81.7% and 90.2% of patients in the primary care physician, diabetology and cardiology cohorts, respectively).

Conclusion: LDL-C levels were uncontrolled in most patients with hyperlipidaemia. Analysis of the 'distance to LDL-C goal' showed that most patients required a substantial LDL-C level reduction to achieve their LDL-C goal.

Background: Reperfusion injury, characterized by oxidative stress and inflammation, poses a significant challenge in cardiac surgery with cardiopulmonary bypass (CPB). Deferoxamine, an iron-chelating compound, has shown promise in mitigating reperfusion injury by inhibiting iron-dependent lipid peroxidation and reactive oxygen species (ROS) production.

Objectives: The objective of our study was to analyze and evaluate both the efficacy and safety of a new and promising intervention, that is, deferoxamine for ischemia-reperfusion injury (I/R).

Design: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines are used to perform the study.

Data sources and methods: We conducted a systematic review following PRISMA guidelines to assess the efficacy and safety of deferoxamine in reducing I/R injury following CPB. A comprehensive search of electronic databases, namely, PubMed, Scopus, and Embase, yielded relevant studies published until August 18, 2023. Included studies evaluated ROS production, lipid peroxidation, cardiac performance, and morbidity outcomes.

Results: (a) ROS production: Multiple studies demonstrated a statistically significant decrease in ROS production in patients treated with deferoxamine, highlighting its potential to reduce oxidative stress. (b) Lipid peroxidation: Deferoxamine was associated with decreased lipid peroxidation levels, indicating its ability to protect cardiac tissue from oxidative damage during CPB. (c) Cardiac performance: Some studies reported improvements in left ventricular ejection fraction and wall motion score index with deferoxamine.

Conclusion: Our review shows that deferoxamine is an efficacious and safe drug that can be used to prevent myocardial I/R injury following CPB. It also highlights the need for trials on a larger scale to develop potential strategies and guidelines on the use of deferoxamine for I/R injury.

Arterial aneurysms remain a significant public health problem because they often result in death when ruptured; therefore, they require immediate medical treatment. Endovascular aneurysm repair (EVAR) has recently become the primary treatment option, owing to the fewer side effects compared to those with open surgery. However, stents used for conventional EVAR often cause side-branch occlusion, which alters the perfusion of vital organs. Recently, multilayer flow modulator (MFM) stents have been used as a new treatment for arterial aneurysms. These stents appear to be feasible owing to their unique design consisting of an uncoated three-dimensionally braided multilayered structure. MFM stents generally remodulate laminar flow and reduce the flow velocity in the aneurysmal sac, leading to thrombosis, which causes the aneurysm to shrink over time. Thus, they reduce the risk of mortality. Moreover, they reduce morbidity by preserving the side-branch blood flow. They can be easily applied to complex aneurysms and are ready to use without customization, which shortens the waiting time for interventions. This study aimed to evaluate the role of MFM stents in the treatment of arterial aneurysms based on available data.

Atrial fibrillation (AF) is common and warrants consideration of oral anticoagulant (OAC) medication. Usually, the decision is straightforward, following the pathway outlined in the European Society of Cardiology's guideline; however, certain situations fall outside of this evidence base - such as a diagnosis of subclinical AF made via implanted devices or wearable electrocardiogram monitors, or alternatively diagnosis of 'secondary AF' following a major stressor. Subclinical AF is associated with stroke, though not to the extent of clinical AF, and the benefits of anticoagulation appear to be lower. Longer episodes are more clinically meaningful, and recent randomised controlled trials have demonstrated that some patients derive benefit from OAC. Similarly, when AF is triggered by sepsis or non-cardiac surgery, specific evidence supporting OAC initiation is lacking and clinician behaviour is variable. Observational data demonstrate poorer outcomes in these patients, implying that the perception of a transient, reversible phenomenon may not be correct. Contrastingly, cardiac surgery very frequently induces AF, and the benefits of anticoagulation rarely outweigh the risks of bleeding. Following ischaemic stroke, recent evidence suggests that early (re-)initiation of OAC should be considered as this does not increase the risk of haemorrhagic transformation as previously hypothesised. This narrative review summarises the available literature and outlines, where possible, practical advice for clinicians facing these common clinical dilemmas.

Background: Heart failure (HF) is a highly prevalent disease, among the primary factors contributing to morbidity and death. One of its types is heart failure with preserved ejection fraction (HFpEF) comprising 40%-50% of newly diagnosed HF cases. Despite the high prevalence of HFpEF, there is still a lack of knowledge regarding the best drugs and treatment approaches to be used. However, the sodium-glucose co-transporter 2 (SGLT2) inhibitors could be a promising treatment.

Objectives: To examine SGLT2 inhibitors' effect on hospitalization, cardiovascular death, and estimated glomerular filtration rate (eGFR) in HFpEF patients.

Search methods: We conducted searches for randomized controlled trials (RCTs) in PubMed, Embase, Scopus, and Web of Science up to July 2024.

Selection criteria: We chose RCTs that examined the effects of SGLT2 inhibitors and placebo in individuals with higher than 40% ejection fraction (HFpEF).

Data collection and analysis: The methodology for the systematic review and meta-analysis was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.

Main results: We included 8 studies with 16,509 participants. Drugs examined in our paper included empagliflozin, dapagliflozin, sotogliflozin, and ertugliflozin. Various outcomes were analyzed in different papers. However, different SGLT2 inhibitors lead to a decreased risk of cardiovascular hospitalization and kidney injury. Our meta-analysis showed a decreased risk of cardiovascular hospitalization but not death due to cardiovascular causes or other causes. These results were regardless of baseline status of eGFR, systolic blood pressure, atrial fibrillation or flutter, diabetes mellitus, sex, body mass index, and nt-proBNP. The included studies were of moderate to high quality.

Conclusion: For individuals with HFpEF, SGLT2 inhibitors have been proven to be a safe and effective medication. However, more studies are needed for longer durations, reporting adverse events, effects on exercise tolerance, and other secondary outcomes.

Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: 'dabigatran', 'apixaban', 'rivaroxaban', 'edoxaban', 'gene polymorphism', 'pharmacogenetics', 'ABCB1', 'CES1', 'SULT1A', 'ABCG2', and 'CYP3A4'. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.

Cardiac fibrosis is a pivotal cardiovascular disease (CVD) process and represents a notable health concern worldwide. While the complex mechanisms underlying CVD have been widely investigated, recent research has highlighted microRNA-21's (miR-21) role in cardiac fibrosis pathogenesis. In this narrative review, we explore the molecular interactions, focusing on the role of miR-21 in contributing to cardiac fibrosis. Various signaling pathways, such as the RAAS, TGF-β, IL-6, IL-1, ERK, PI3K-Akt, and PTEN pathways, besides dysregulation in fibroblast activity, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs cause cardiac fibrosis. Besides, miR-21 in growth factor secretion, apoptosis, and endothelial-to-mesenchymal transition play crucial roles. miR-21 capacity regulatory function presents promising insights for cardiac fibrosis. Moreover, this review discusses numerous approaches to control miR-21 expression, including antisense oligonucleotides, anti-miR-21 compounds, and Notch signaling modulation, all novel methods of cardiac fibrosis inhibition. In summary, this narrative review aims to assess the molecular mechanisms of cardiac fibrosis and its essential miR-21 function.

Background and objectives: California is one of a few states with mandatory reporting of mortality after coronary artery bypass graft (CABG) surgery. The Affordable Care Act restructured Medicaid, preferentially penalizing patients experiencing poverty because payments to hospitals for isolated surgical events overshadow payments to primary care clinicians. We propose outcomes are superior when hospital networks organize surgical episodes within the context of primary care inside that same network.

Design and methods: We listed factors impacting outcomes after CABG. CABG surgery outcome depends upon the integration of issues beginning years preoperatively and extending for decades. Therefore, we studied one health maintenance organization (HMO) from 2009 to 2020 compared to surrounding individual hospitals. We divided 58 hospitals in Northern California in 2009 according to income and population. To focus on changes introduced because of COVID-19, we compared a public database for the subset in 2009 for any relationship between poverty in a zip code and low volumes of CABG in that area to overall mortality in 2020. First, we defined low-income zip codes as those with a higher rate of poverty than the state average or with a lower per capita average income, per Census Bureau. Second, low volume was defined as a population under 165,000 because a hospital adjacent to a larger community can easily transfer care, sharing surgeons and processes. Third, we defined low volume as fewer than 180 CABG per year.

Results: Our qualitative evidence synthesis reveals that informal communication and hospital HMO policies improve CABG outcomes. In our small pilot data, Chi-square analysis showed higher crude mortality rates in 1507 CABG in 17 low-income low-volume hospitals versus 8163 CABG in the other 41 Northern California hospitals (2.72% vs 1.69%, p = 0.0064). Low-income low-volume hospitals had a relative mortality risk of 1.61 (95% CI: 1.14-2.27). These hospitals had a mean mortality rate of 3.79%, readmission 11.12%, and stroke 1.84%. A patient undergoing CABG in a low-income low-volume hospital has a 61% higher chance of dying. The number needed to treat analysis shows that one life can potentially be saved for every 97 patients referred to another institution.

Conclusion: We describe features of an HMO that contribute to up to fourfold lower mortality rates.

Objective: We aim to evaluate the quality of patient-reported outcomes included in randomized control trials for the treatment of congestive heart failure using the International Society for Quality of Life Research (ISOQOL) checklist, a validated tool for critically appraising the quality of patient-reported outcomes.

Design: We performed a cross-sectional analysis of 65 randomized control trials with patient-reported outcomes for drug intervention trials for treating congestive heart failure.

Setting: N/A.

Participants: N/A.

Main outcome measures: The primary outcome of this study was to evaluate the reporting completeness of patient-reported outcomes in congestive heart failure clinical trials with drug interventions according to the ISOQOL checklist.

Results: Our search returned 1114 studies, of which, 65 are included in the analysis. The average completion of the ISOQOL reporting standards was 44.51%. Higher completion of the ISOQOL patient-reported outcome standards was observed in the clinical trials with patient-reported outcomes as primary endpoints compared to the clinical trials with patient-reported outcomes as a secondary endpoint. The multivariable regression model showed that clinical trials with patient-reported outcomes as a primary endpoint had a 21.46% better completion percentage (t = 4.45, p ⩽ 0.001) when controlling for PRO recording duration and trial registration. Eight (8/65, 12.31%) of the clinical trials met the satisfaction criteria of completing two-thirds of the ISOQOL patient-reported outcomes reporting standards. All of these RCTs had a patient-reported outcome as a primary endpoint.

Conclusion: Our analysis of the reporting of patient-reported outcomes in congestive heart failure clinical trials with drug interventions suggests that the quality of reporting is suboptimal. This evidence of substandard reporting of patient-reported outcomes is disconcerting as it reduces the transparency of randomized control trials, which are considered the foundation of evidenced-based medicine. Inadequate reporting may result in clinicians implementing misrepresented or incomplete evidence into clinical practice. Validated reporting tools, such as the ISOQOL, can be used by trialists and clinicians alike to improve and critically appraise the reporting of patient-reported outcomes in randomized control trials.

Trial registration: N/A.

Background: Sacubitril/valsartan (S/V) is a cornerstone treatment for heart failure (HF). Beneficial effects on hospitalization rates, mortality, and left ventricular remodeling have been observed in patients with heart failure and reduced ejection fraction (HFrEF). Despite the positive results, the influence of S/V on renal function during long-term follow-up has received little attention.

Aims: We investigated the long-term effects of S/V therapy on renal function in a large cohort of patients with HFrEF. Additionally, we examined the effects of the drug in patients with chronic kidney disease (CKD) compared to those with preserved renal function and identified primary risk characteristics.

Methods: We studied 776 outpatients with HFrEF and left ventricular ejection fraction (LVEF) <40% from an observational registry of the Italian Society of Cardiology, all receiving optimized standard-of-care therapy with S/V. The patients were included in a multicentric open-label registry from 11 Italian academic hospitals. Kidney function was evaluated at baseline, after 6 months of S/V, and at 4 years. Patients were followed-up through periodic clinical visits.

Results: During a 48-month follow-up period, 591 patients remained stable and 185 patients (24%) experienced adverse events (85 deaths and 126 hospitalizations). S/V therapy marginally affects renal function during the follow-up period (estimated glomerular filtration rate (eGFR) at baseline 72.01 vs eGFR at follow-up 70.38 ml/min/m², p = 0.01; and creatinine was 1.06 at baseline vs 1.10 at follow-up, p < 0.04). Among patients who maintained preserved renal function, 35% were in Dose 3 and 10% dropped out of S/V therapy (p < 0.006). Univariate analysis showed that Drop-out of S/V (HR 2.73 [2.01, 3.71], p < 0.001), history of previous HF hospitalization (HR 1.75 [1.30, 2.36], p < 0.001), advanced NYHA class (HR 2.14 [1.60, 2.86], p < 0.001), NT-proBNP values >1000 pg/ml (HR 1.95[1.38, 2.77], p < 0.001), furosemide dose >50 mg (HR 2.04 [1.48, 2.82], p < 0.001), and creatinine values >1.5 mg/dl occurred during follow-up (HR 1.74 [1.24, 2.43], p < 0.001) were linked to increased risk. At multivariable analysis, increased doses of loop diuretics, advanced NYHA class, creatinine >1.5 mg/dl, and atrial fibrillation were independent predictors of adverse events.

Conclusion: Long-term S/V therapy is associated with improved outcomes and renal protection in patients with HFrEF. This effect is more pronounced in patients who tolerate escalating doses. The positive effects of the drug are maintained in both CKD and preserved renal function. Future research may study the safety and underlying causes of current protection.