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1.
Role of ranolazine in heart failure: From cellular to clinic perspective.
Kaplan, A, Amin, G, Abidi, E, Altara, R, Booz, GW, Zouein, FA
European journal of pharmacology. 2022;:174787
Abstract
Ranolazine was approved by the US Food and Drug Administration as an antianginal drug in 2006, and has been used since in certain groups of patients with stable angina. The therapeutic action of ranolazine was initially attributed to inhibitory effects on fatty acids metabolism. As investigations went on, however, it developed that the main beneficial effects of ranolazine arise from its action on the late sodium current in the heart. Since late sodium currents were discovered to be involved in various heart pathologies such as ischemia, arrhythmias, systolic and diastolic dysfunctions, and all these conditions are associated with heart failure, ranolazine has in some way been tested either directly or indirectly on heart failure in numerous experimental and clinical studies. As the heart continuously remodels following any sort of severe injury, the inhibition by ranolazine of the underlying mechanisms of cardiac remodeling including ion disturbances, oxidative stress, inflammation, apoptosis, fibrosis, metabolic dysregulation, and neurohormonal impairment are discussed, along with unresolved issues. A projection of pathologies targeted by ranolazine from cellular level to clinical is provided in this review.
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2.
Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients.
Corrado, E, Dattilo, G, Coppola, G, Morabito, C, Bonni, E, Zappia, L, Novo, G, de Gregorio, C
European journal of clinical pharmacology. 2022;(1):19-25
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Abstract
PURPOSE Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. METHODS This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. RESULTS A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11-13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A (p < 0.001), and from 29 to 82% in group B (p < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. CONCLUSION One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B.
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Race, Ancestry, and Risk: Targeting Prevention to Address Heart Failure Disparities.
Youmans, QR, Lloyd-Jones, DM, Khan, SS
Circulation. Heart failure. 2022;(1):e008741
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The Efficacy and Safety of Sacubitril/Valsartan in Heart Failure Patients: A Review.
Zhang, R, Sun, X, Li, Y, He, W, Zhu, H, Liu, B, Zhang, A
Journal of cardiovascular pharmacology and therapeutics. 2022;:10742484211058681
Abstract
Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has been approved for the treatment of HF. At present, there have been few systematic and detailed reviews discussing the efficacy and safety of sacubitril/valsartan in HF. In this review, we first introduced the pharmacological mechanisms of sacubitril/valsartan, including the reduction in the degradation of natriuretic peptides in the natriuretic peptide system and inhibition of the renin-angiotensin system. Then, we summarized the efficacy of sacubitril/valsartan in HF patients with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) including the reduction in risks of mortality and hospitalization, reversal of cardiac remodeling, regulation of biomarkers of HF, improvement of the quality of life, antiarrhythmia, improving renal dysfunction and regulation of metabolism. Finally, we discussed the safety and tolerability of sacubitril/valsartan in the treatment of HFrEF or HFpEF. Compared with ACEIs/ARBs or placebo, sacubitril/valsartan showed good safety and tolerability, although the risk of hypotension might be high. In conclusion, the overwhelming majority of studies show that sacubitril/valsartan is effective and safe in the treatment of HFrEF patients but that it has little benefit in HFpEF patients. Sacubitril/valsartan will probably be a promising anti-HF drug in the near future.
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Mechanisms of action of SGLT2 inhibitors and their beneficial effects on the cardiorenal axis.
Gronda, E, Lopaschuk, GD, Arduini, A, Santoro, A, Benincasa, G, Palazzuoli, A, Gabrielli, D, Napoli, C
Canadian journal of physiology and pharmacology. 2022;(2):93-106
Abstract
Large clinical studies conducted with sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and heart failure with reduced ejection fraction have demonstrated their ability to achieve both cardiac and kidney benefits. Although there is huge evidence on SGLT2i-mediated clinical benefits both in diabetic and non-diabetic patients, the pathophysiological mechanisms underlying their efficacy are still poorly understood. Some favorable mechanisms are likely due to the prompt glycosuric action which is associated with natriuretic effects leading to hemodynamic benefits as well as a reduction in glomerular hyperfiltration and renin-angiotensin-aldosterone system activation. In addition to the renal mechanisms, SGLT2i may play a relevant role in cardiorenal axis protection by improving the cardiomyocyte metabolism, by exerting anti-fibrotic and anti-inflammatory actions, and by increasing cardioprotective adipokine expression. New studies will be needed to better understand the specific molecular mechanisms that mediate the SGLT2i favorable effects in patients suffering diabetes. Our aim is to first discuss about the molecular mechanisms underlying the cardiovascular benefits of SGLT2i in each of the main organs involved in the cardiorenal axis. Furthermore, we update on the most recent clinical trials evaluating the beneficial effects of SGLT2i in treatment of both diabetic and non-diabetic patients suffering heart failure.
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A Systematic Review on the Use of Sacubitril/Valsartan Initiated Prior to Discharge in Hospitalized Patients With Heart Failure.
Thornby, KA, Maksutovic, NM
The Annals of pharmacotherapy. 2021;(3):378-389
Abstract
OBJECTIVE Systematically review the evidence of sacubitril/valsartan initiated in the hospital setting prior to discharge in patients with acute decompensated heart failure (HF). DATA SOURCES A literature search using keywords related to sacubitril/valsartan, HF, and inpatient use was performed using MEDLINE, CINAHL, and Google Scholar from inception through May 8, 2020. STUDY SELECTION AND DATA EXTRACTION Eligible studies included patients initiated on sacubitril/valsartan while inpatient and reported efficacy and safety outcomes. DATA SYNTHESIS A total of 10 articles were included for study review, of which 9 were full text and 1 was a conference poster. Key outcomes of interest were related to tolerability, N-terminal proB-type natriuretic peptide (NT-proBNP), functional capacity, target dose attainment, or rehospitalization rates. NT-proBNP levels were improved in 4 trials, and the results of functional capacity were mixed based on 2 studies. Rehospitalization rates were reported as secondary outcomes, and only 1 large study showed numerical and statistical improvement. The most frequent dose initiated prior to discharge was sacubitril/valsartan 24/26 mg twice daily. Hypotension was the most commonly reported adverse drug reaction and was commonly cited as a reason for not tolerating inpatient initiation with sacubitril/valsartan therapy. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE Inpatient initiation of sacubitril/valsartan may improve surrogate and clinical outcomes after hemodynamic stabilization. Clinicians should consider patient-specific factors to ensure that benefits outweigh the risks and monitor for hypotension when initiated prior to hospital discharge. CONCLUSION Initiating inpatient treatment with sacubitril/valsartan after hemodynamic stabilization is reasonable based on available evidence.
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Efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease: A protocol of randomized controlled trial.
Guo, B, Yang, T, Nan, J, Huang, Q, Wang, C, Xu, W
Medicine. 2021;(7):e24414
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Abstract
BACKGROUND Coronary heart disease is a serious cardiovascular disease. There is coronary atherosclerosis, resulting in lumen stenosis, blockage, and then the symptoms of insufficient blood supply and hypoxia in the myocardium. Chronic heart failure is a kind of syndrome with abnormal ventricular filling and ejection function, which is the final stage of the development of coronary heart disease. At present, the treatment plan of Western medicine can significantly reduce the hospitalization rate, but it is still not satisfactory for the prognosis and mortality of patients. Shenfu injection has advantages in the treatment of heart failure in patients with coronary heart disease, but there is a lack of standard clinical studies to verify it, so the purpose of this randomized controlled study is to evaluate the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. METHODS This is a prospective randomized controlled trial to study the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. The patients will be randomly divided into a treatment group and the control group according to 1:1, in which the treatment group is treated with Shenfu injection combined with sodium nitroprusside, and the control group is treated with sodium nitroprusside alone. Both groups will be treated with standard treatment for 7 days and followed up for 30 days to pay attention to their efficacy and safety indexes. The observation indexes include TCM syndrome score, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction, brain natriuretic peptide, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, stroke volume, adverse reactions and so on. We will use SPSS 25.0 software for data analysis. DISCUSSION This study will evaluate the efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. The results of this experiment will provide a clinical basis for Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in coronary heart disease. TRIAL REGISTRATION DOI 10.17605/OSF.IO/4KNG3.
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Efficacy and safety of sacubitril-valsartan in patients with heart failure: a systematic review and meta-analysis of randomized clinical trials: A PRISMA-compliant article.
Lin, J, Zhou, J, Xie, G, Liu, J
Medicine. 2021;(52):e28231
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Abstract
BACKGROUND To investigate the efficacy and safety of sacubitril-valsartan in patients with heart failure, relevant randomized clinical trials (RCTs) were analyzed. METHODS We used Cochrane Library, PubMed web of science, CNKI, VIP, Medline, ISI Web of Science, CBMdisc, and Wanfang database to conduct a systematic literature research. A fixed-effects model was used to evaluate the standardized mean differences (SMDs) with 95% confidence intervals. We conducted sensitivity analysis and analyzed publication bias to comprehensively estimate the efficacy and safety of sacubitril-valsartan in patients with heart failure. RESULTS Among 132 retrieved studies, 5 relevant RCTs were included in the meta-analysis. The result showed that left ventricular ejection fraction (LVEF) was improved after sacubitril-valsartan in patients with heart failure, with an SMD (95% CI of 1.1 [1.01, 1.19] and P < .00001 fixed-effects model). Combined outcome indicators showed that, combined outcome indicators showed that, compared with control group, the left ventricular volume index (LAVI) (WMD = -2.18, 95% CI [-3.63, -0.74], P = .003), the E/e' (WMD = -1.01, 95% CI [-1.89, -0.12], P = .03), the cardiovascular death (RR = 0.89, 95% CI [0.83, 0.96], P = .003], and the rehospitalization rate of heart failure (RR = 0.83, 95% CI [0.78, 0.88], P < .01) decreased more significantly, but it had no effect on renal function (WMD = 0.74, 95% CI [0.54, 1.01], P = .06). CONCLUSIONS The present meta-analysis suggested that sacubitril-valsartan may improve the cardiac function of heart failure. Given the limited number of included studies, additional large sample-size RCTs are required to determine the long-term effect of cardiac function of sacubitril-valsartan in patients with heart failure.
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Sodium-Glucose Cotransporter Inhibitors in Non- Diabetic Heart Failure: A Narrative Review.
Dahal, R, Acharya, Y, Mukherjee, D
Cardiovascular & hematological disorders drug targets. 2021;(1):1-6
Abstract
BACKGROUND Heart failure (HF) is one of the leading public health problems with a substantial burden in the global healthcare system. Although significant efforts are based on prevention, early recognition, and proper management of HF, the worldwide surge of risk factors like hypertension, diabetes, and obesity has further complicated the existing problem. OBJECTIVE This study aims to define the role of the sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-diabetic HF. METHODS We performed a comprehensive literature review to examine the available evidence in the clinical implications of SGLT2 inhibitors in non-diabetic HF using the online databases (PubMed and Embase). RESULTS We identified two RCTs-DAPA-HF and DEFINE-HF, which were conducted to analyze the net clinical benefit of dapagliflozin in non-diabetic HF patients. Although we could not study the composite effects of these studies due to the difference in outcome measures, the individual outcomes look promising. The number needed to treat (NNT) to prevent one primary event was 21 (95% CI: 15 to 38) in the DAPA study. In DEFINE HF study, responder analysis showed a significant proportion of patients in the treatment arm experienced improvements in the functional status with clinically meaningful improvement in KCCQ-OS by 3.7 points and KCCQ-CS by 4.6 points with NNT of 10 and 7, respectively, at 12 weeks. Both studies also showed low safety concerns in patients without T2D. CONCLUSION The outcomes of the two RCTs, DAPA-HF and DEFINE-HF, that studied the effects of SGLT2 inhibitors in non-diabetic HF showed promising clinical outcomes. Although we are waiting for other prospective RCTs to reflect similar results and safety profiles, it seems the SGLT2 inhibitors can have broader clinical implications in managing non-diabetic HF with improved cardiovascular outcomes.
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Nocturnal Hypertension and Heart Failure: Mechanisms, Evidence, and New Treatments.
Kario, K, Williams, B
Hypertension (Dallas, Tex. : 1979). 2021;(3):564-577
Abstract
Heart failure (HF) is a common condition with an increasing prevalence. Despite a variety of evidence-based treatments for patients with HF with reduced ejection fraction, morbidity and mortality rates remain high. Furthermore, there are currently no treatments that have yet been shown to reduce complication and death rates in patients who have HF with preserved ejection fraction. Hypertension is a common comorbidity in patients with HF, contributing to disease development and prognosis. For example, hypertension is closely associated with the development of left ventricular hypertrophy, which an important precursor of HF. In particular, nighttime blood pressure (BP) appears to be an important, modifiable risk factor. Both nighttime BP and an abnormal circadian pattern of nighttime BP dipping have been shown to predict development of HF and the occurrence of cardiovascular events, independent of office BP. Key mechanisms for this association include sodium handling/salt sensitivity and increased sympathetic activation. These pathogenic mechanisms are targeted by several new treatment options, including sodium-glucose cotransporter 2 inhibitors, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and renal denervation. All of these could form part of antihypertensive strategies designed to control nighttime BP and contribute to the goal of achieving perfect 24-hour BP management. Nevertheless, additional research is needed to determine the effects of reducing nighttime BP and improving the circadian BP profile on the rate of HF, other cardiovascular events, and mortality.