Bilateral renal artery revascularisation in heart failure.

Renal artery stenosis can complicate the management of heart failure with reduced ejection fraction, as it is a conventional contraindication to the use of ACE inhibitors. We report a case in which bilateral renal artery revascularisation allowed the safe reintroduction of enalapril (and subsequently sacubitril valsartan) in a patient with severe left ventricular systolic dysfunction. There is a role for renal artery angioplasty in selected patients to allow optimal medical therapy for patients with heart failure due to impaired systolic function.

Role and molecular mechanism of Salvia miltiorrhiza associated with chemical compounds in the treatment of diabetes mellitus and its complications: A review.

Diabetes mellitus (DM) is one of the most prevalent diseases worldwide, greatly impacting patients' quality of life. This article reviews the progress in Salvia miltiorrhiza, an ancient Chinese plant, for the treatment of DM and its associated complications. Extensive studies have been conducted on the chemical composition and pharmacological effects of S miltiorrhiza, including its anti-inflammatory and antioxidant activities. It has demonstrated potential in preventing and treating diabetes and its consequences by improving peripheral nerve function and increasing retinal thickness in diabetic individuals. Moreover, S miltiorrhiza has shown effectiveness when used in conjunction with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), and statins. The safety and tolerability of S miltiorrhiza have also been thoroughly investigated. Despite the established benefits of managing DM and its complications, further research is needed to determine appropriate usage, dosage, long-term health benefits, and safety.

Initiation and continuation of pharmacological therapies in patients hospitalized for heart failure in Japan.

Currently, the utilization patterns of medications for heart failure (HF) after worsening HF events remain unelucidated in Japan. Here, we conducted a retrospective cohort study evaluating the changes in HF drug utilization patterns in 6 months before and after hospitalizations for HF. The adherence to newly initiated HF medications was evaluated based on the proportion of days covered (PDC) and persistence as continuous treatment episodes among new users. The study included 9091 patients hospitalized for HF between January 2016 and September 2019, including 2735 (30.1%) patients who were newly prescribed at least one HF medication after hospitalization. Despite increases in the use of foundational HF therapy (beta-blockers, angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers, or mineralocorticoid receptor antagonists), 35.6% and 7.6% of patients were treated with the HF foundational monotherapy or diuretics alone after hospitalization, respectively. The mean PDC of newly initiated HF medications ranged from 0.57 for thiazide diuretics to 0.77 for sodium-glucose cotransporter-2 inhibitors. Continuous use of HF medications during the first year after initiation was observed in 30-60% of patients. The mean PDC and one-year continuous HF medication use were consistently lower in patients aged ≥ 75 years and in patients with a history of HF hospitalization for all HF medication classes except for tolvaptan and digoxin. Despite the guideline recommendations of HF pharmacotherapy, both treatment and adherence were suboptimal after HF hospitalization, especially in vulnerable populations such as older patients and those with prior HF hospitalizations.

Heart failure management with ß-blockers: can we do better?

Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including ß-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. ß-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, ß-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, ß-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of ß-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a ß-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.

Enteropathy and intestinal malabsorption in patients treated with antihypertensive drugs. A retrospective cohort study.

OBJECTIVES: To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea. METHODS: In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021. RESULTS: Of the 44,775 patients, 51 (0.11%) were observed to have enteropathy or intestinal malabsorption. Compared with the ACEI group, the adjusted odds ratios (ORs) for enteropathy and intestinal malabsorption were OR=1.313 (95% confidence interval [CI]: [0.188-6.798], p=0.893) for olmesartan, OR=0.915 (95% CI: [0.525-1.595], p=0.754) for the other ARBs, OR=0.928 (95% CI: [0.200-4.307]; p=0.924) for the CCB, and OR=0.663 (95% CI: [0.151-2.906]; p=0.586) for the BBs group. These findings were adjusted for factors such as age, gender, duration of antihypertensive medication, and comorbidities. CONCLUSION: In a retrospective cohort study of patients on antihypertensive medications, no significant difference was found in the incidence of enteropathy or intestinal malabsorption when ACEI was compared to olmesartan, other ARBs, CCB, and BBs.

[Decompensation of Heart Failure in "Fragile" Patients: Clinical Features and Approaches to Therapy].

AIM: To evaluate the impact of frailty syndrome (FS) on the course of acute decompensated heart failure (ADHF) and the quality of drug therapy before discharge from the hospital in patients with reduced and moderately reduced left ventricular ejection fraction (LVEF). MATERIAL AND METHODS: This open prospective study included 101 patients older than 75 years with reduced and mid-range LVEF hospitalized for decompensated chronic heart failure (CHF). FS was detected during the outpatient follow-up and identified using the Age is Not a Hindrance questionnaire, the chair rise test, and the One Leg Test. The "fragile" group consisted of 54 patients and the group without FS included 47 patients. Clinical characteristics of patients were compared, and the prescribing rate of the main drugs for the treatment of CHF was assessed upon admission to the hospital. The sacubitril/valsartan or dapagliflozin therapy was initiated in the hospital; prescribing rate of the quadruple therapy was assessed upon discharge from the hospital. Patients with reduced LVEF were followed up for 30 days, and LVEF was re-evaluated to reveal possible improvement due to optimization of therapy during hospitalization. Statistical analysis was performed with the SPSS 23.0 software. RESULTS: The main causes for decompensation did not differ in patients of the compared groups. According to the correlation analysis, FS was associated with anemia (r=0.154; p=0.035), heart rate ≥90 bpm (r=0.185; p=0.020), shortness of breath at rest (r =0.224; p=0.002), moist rales in the lungs (r=0.153; p=0.036), ascites (r=0.223; p=0.002), increased levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP) (r= 0.316; p<0.001), hemoglobin concentration <120 g / l (r=0.183; p=0.012), and total protein <65 g / l (r=0.153; p=0.035) as measured by lab blood tests. Among patients with LVEF ≤40 % in the FS group (n=33) and without FS (n=33), the quadruple therapy was a part of the treatment regimen at discharge from the hospital in 27.3 and 3.0 % of patients, respectively (p=0.006). According to the 30-day follow-up data, improvement of LVEF was detected in 18.2% of patients with LVEF ≤40% in the FS group and 12.1% of patients with LVEF ≤40% in the FS-free group (p=0.020). In patients with LVEF 41-49 % in the FS (n=21) and FS-free (n=14) groups, the prescribing rate of the optimal therapy, including sacubitril/valsartan, sodium-glucose cotransporter 2 inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, no statistically significant differences were detected (14.3 and 7.1 %, respectively; p=0.515) at discharge from the hospital. CONCLUSION: Patients with ADHF and FS showed more pronounced clinical manifestations of decompensation, anemia, heart rate ≥90 beats/min, and higher levels of NT-proBNP upon admission. The inpatient therapy with sacubitril/valsartan or dapagliflozin was more intensively initiated in FS patients with reduced LVEF. An individualized approach contributed to achieving a prescribing rate of sacubitril/valsartan of 39.4%, dapagliflozin of 39.4%, and quadruple therapy of 27.3% upon discharge from the hospital.

Sacubitril/valsartan can improve the cardiac function in heart failure patients with a history of cancer: An observational study.

Sacubitril/Valsartan, the combination of angiotensin receptor inhibitor and neprilysin inhibitor, is now becoming the class 1 recommendation for HFrEF. Some studies have shown the positive effect of Sacubitril/Valsartan on HFrEF cancer patients, while there is devoid of evidence about the effect of this drug in aged cancer patients with HFmrEF and HFpEF. By searching the patients with a diagnosis of both cancer and Heart failure (HF) over 65, the patients who had received treatment with Sacubitril/Valsartan were selected as the candidates for Sacubitril/Valsartan group, and the patients who had received conventional HF therapy without Sacubitril/Valsartan were chosen as the control group. Data were collected for up to 9 months. We filtered 38 patients and 50 patients valid for Sacubitril/Valsartan group and control group, respectively. After initiation of heart failure management, our study found a better cardiac condition in Sacubitril/Valsartan group, having better LVEF, LVFS, NT-proBNP in 3rd, 6th, 9th month (P < .05) and better NYHA function classification after the treatment. We also observed fewer cases of deterioration on LAD (P = .029) and LVEDD (P = .023) in Sacubitril/Valsartan group. In subgroup analysis, our study showed that all 3 kinds of HF patients had better LVEF, LVFS, and NT-proBNP in Sacubitril/Valsartan group (P < .05). Our study further indicated that Sacubitril/Valsartan can improve cardiac function and benefit cardiac remolding in aged cancer patients of all 3 kinds of HF. This is the first study to provide new evidence for the use of Sacubitril/Valsartan in aged cancer patients of 3 kinds of HF.

Cardiovascular/anti-inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer. METHODS: We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023. MAIN OUTCOMES AND MEASURES: The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival. RESULTS: We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival). CONCLUSIONS AND RELEVANCE: Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.

Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study.

INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Management of Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor: Strategies to Maintain Chronic Kidney Disease Patients with Type II Diabetes on Therapy.

BACKGROUND: According to the Centers for Disease Control and Prevention (CDC), diabetes affects approximately 37.3 million individuals in the USA, with another estimated 96 million people having a prediabetic state. Furthermore, one or two out of three adult Americans exhibit metabolic syndrome or an insulin-resistant state, depending on their age group. SUMMARY: Chronic kidney disease (CKD) represents a complication often associated with type II diabetes or the insulin-resistant condition, typically identifiable through proteinuria. Proteinuria serves as both a marker and a contributing factor to kidney damage, and it significantly heightens the risk of cardiovascular (CV) events, including atherosclerosis, heart attacks, and strokes. Renin-angiotensin-aldosterone system inhibitors (RAASis) have demonstrated clinical efficacy in lowering blood pressure, reducing proteinuria, and slowing CKD progression. However, hyperkalemia is a common and serious adverse effect associated with using RAASi. KEY MESSAGES: It is imperative to establish personalized management strategies to enable patients to continue RAASi therapy while effectively addressing hyperkalemia risk. Healthcare professionals must be careful not to inadvertently create a low renal perfusion state, which can reduce distal nephron luminal flow or luminal sodium concentration while using RAASi. Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), such as finerenone, are demonstrated to delay CKD progression and reduce CV complications, all while mitigating the risk of hyperkalemia. Additionally, maintaining a routine monitoring regimen for serum potassium levels among at-risk patients, making dietary adjustments, and considering the adoption of newer potassium-binding agents hold promise for optimizing RAASi therapy and achieving more effective hyperkalemia management.

Effect of Renin-Angiotensin System Blockers in Acute Myocardial Infarction Patients with Acute Kidney Injury.

INTRODUCTION: Renin-angiotensin system blockers (RASBs) are known to improve mortality after acute myocardial infarction (AMI). However, there remain uncertainties regarding treatment with RASBs after AMI in patients with renal dysfunction and especially in the setting of acute kidney injury (AKI). METHODS: Patients from a multicenter AMI registry undergoing percutaneous coronary intervention in Korea were stratified and analyzed according to the presence of AKI, defined as an increase in serum creatinine levels of ≥0.3 mg/dL or ≥50% increase from baseline during admission, and RASB prescription at discharge. The primary outcome of interest was 5-year all-cause mortality. RESULTS: In total 9,629 patients were selected for initial analysis, of which 2,405 had an episode of AKI. After adjustment using multivariable Cox regression, treatment with RASBs at discharge was associated with decreased all-cause mortality in the entire cohort (hazard ratio [HR] 0.849, confidence interval [CI] 0.753-0.956), but not for the patients with AKI (HR 0.988, CI 0.808-1.208). In subgroup analysis, RASBs reduced all-cause mortality in patients with stage I AKI (HR 0.760, CI 0.584-0.989) but not for stage II and III AKI (HR 1.200, CI 0.899-1.601, interaction p value 0.002). Similar heterogeneities between RASB use and AKI severity were also observed for other clinical outcomes of interest. CONCLUSION: Treatment with RASBs in patients with AMI and concomitant AKI is associated with favorable outcomes in non-severe AKI, but not in severe AKI. Further studies to confirm these results and to develop strategies to minimize the occurrence of adverse effects arising from RASB treatment are needed.

Investigating the use of finerenone in children with chronic kidney disease and proteinuria: design of the FIONA and open-label extension studies.

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. DESIGN: FIONA (NCT05196035; Eudra-CT: 2021-002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months' duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021-002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. CONCLUSION: FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.

Effect of angiotensin-converting enzyme inhibitors versus that of angiotensin receptor blockers on survival in patients undergoing hemodialysis: a nationwide observational cohort study.

BACKGROUND: This study aimed to evaluate the patient survival rates based on the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in a large cohort of patients undergoing maintenance hemodialysis (HD). METHODS: Data from a national HD quality assessment program were used in this retrospective study. The patients were classified into four groups based on the use of renin-angiotensin system blockers (RASBs) as follows: No group, patients without a prescription of any anti-hypertensive drugs including RASBs; Other group, patients with a prescription of anti-hypertensive drugs excluding RASBs; ACEI group, patients with a prescription of an ACEI; and ARB group, patients with a prescription of an ARB. RESULTS: The 5-year survival rates in the no, other, ACEI, and ARB groups were 68.6%, 67.8%, 70.6%, and 69.2%, respectively. The ACEI group had the best patient survival trend among the four groups. In multivariable Cox regression analyses, no differences were observed between the ACEI and ARB groups. Among young patients and patients without diabetes or heart disease, the ACEI group had the best patient survival among the four groups. However, among patients with DM or heart disease, the ARB group had the best patient survival. CONCLUSIONS: Our study found that patients receiving ACEI and ARB had comparable survival. However, patients receiving ARB had better survival in the subgroups of patients with DM or heart disease, and patients receiving ACEI had better survival in the subgroup of young patients or patients without diabetes or heart disease.

Pressure control and treatment interact in the deterioration of incidental visuospatial memory in hypertensive patients.

BACKGROUND: Systemic hypertension (SH) is the main risk factor to cognitive deterioration, whereas visuospatial memory is more vulnerable to ageing. Some antihypertensive agents have a neuroprotector effect, however, such effects could be masked by comorbidities and/or the lack of effective control on the arterial pressure of patients. OBJECTIVE: To assess this, the evaluation of incidental visuospatial memory of SH patients and the relation to the treatment received and the effective control of pressure were made. METHOD: 80 patients (46 woman) were included grouped by the received medication: angiotensin 2 receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI). A multiple correlation analysis between visuospatial scores and clinical variables was made; also, a mixed model analysis (fixed factors: treatment, pressure control, diabetes comorbidity; aleatory factors: age, schooling, months from SH diagnoses). RESULTS: Half of the patients had a controlled pressure, from them the higher proportion received ARB, and a minor number of patients received ACEI. The normotensive patients receiving ACEI were inefficient whereas the hypertensive patients were more efficient. The systolic pressure was negatively related with the visuospatial scores in spite of no correlations occurred with MoCA and Raven tests. CONCLUSIONS: The visuospatial incidental/intentional scores were negatively correlated with systolic pressure. The efficiency in the visuospatial ability depends on the interaction of treatment and effective control of blood pressure. The interaction between treatment and effective pressure control must be taken in count when cognitive deterioration is studied.

ANTECEDENTES: La hipertensión arterial sistémica (HAS) es el principal factor de riesgo para el deterioro cognitivo; por otro lado, la memoria visuoespacial es más vulnerable al envejecimiento. Algunos fármacos antihipertensivos tienen un efecto neuroprotector, pero tal efecto puede enmascararse o bien no manifestarse por comorbilidad o por falta de control efectivo de la presión arterial. OBJETIVO: Evaluar las alteraciones en la memoria visuoespacial incidental de pacientes con HAS en relación con su tratamiento antihipertensivo y su control de la presión. MÉTODO: Se incluyeron 80 pacientes con HAS (46 mujeres), agrupados por su medicación en bloqueadores de los receptores de la angiotensina II (BRA) o inhibidores de la enzima convertidora de angiotensina (IECA). Se realizó un análisis de correlaciones múltiples para los puntajes obtenidos en la prueba de memoria visuoespacial incidental/intencional y un análisis de modelos mixtos (factores fijos: tratamiento, control de la presión y comorbilidad con diabetes; factores aleatorios: edad, escolaridad, meses desde el diagnóstico de HAS y coeficiente intelectual). RESULTADOS: De los pacientes controlados, la mayoría de los que recibían BRA fueron eficientes y los que recibían IECA fueron deficientes. De los que recibían IECA, los descontrolados hipertensos fueron más eficientes que los normotensos. La memoria visuoespacial se correlacionó negativamente con la presión sistólica a pesar de no haber diferencias en MoCA y Raven. CONCLUSIONES: La eficiencia en la memoria visuoespacial dependió de la interacción del tratamiento y el control de la presión. Ambos factores, tratamiento y control efectivo de la presión, deben considerarse en la evaluación del deterioro cognitivo asociado a la HAS.

Association of antihypertensives and Parkinson's disease in a primary care population matched for underlying diagnosis.

PURPOSE: To examine the association of several antihypertensive medication classes with incidence of Parkinson's disease (PD), taking into account possible underlying conditions. METHODS: In a case-control study based on a large primary care database and including 21,981 PD cases and 21,981 non-PD controls matched for age, sex, and possible treatment indications associations with different antihypertensive medication groups, including diuretics, betablockers, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin-II receptor-blockers and PD were examined. RESULTS: Antihypertensive medications overall were associated with a lower risk of subsequent diagnosis of PD (OR: 0.94, 95% CI 0.90-0.97), with the negative association most significant for medications acting on the renin-angiotensin-aldosterone system. A positive association with diagnosis of PD was only seen for betablockers and restricted to those with relatively young age and not in those with longer treatment duration. CONCLUSION: When taking into account underlying diagnoses, antihypertensive medications overall were associated with a reduced incidence of PD.

Impact of angiotensin receptor-neprilysin inhibition (ARNI) in improving ejection fraction and left and right ventricular remodeling in heart failure.

Angiotensin receptor neprilysin inhibitors (ARNI), a new therapeutic class of agents acting on the renin angiotensin aldosterone system (RAAS) and neutral endopeptidase system has been developed in treatment of ventricular remodeling and has attracted considerable attention. The first in class is LCZ696, which is a molecule that combines Valsartan (ARB) and Sacubitril (neprilysin inhibitor) within a single substance. Sacubitril-Valsartan is the first angiotensin receptor enkephalin inhibitors (ARNI), which can block angiotensin II type 1 receptor (AT1R) while inhibiting enkephalin (NEP) and effectively reverse ventricular remodeling in heart failure patients. It has been recommended by the European and American authoritative guidelines on heart failure as Class I for the treatment of chronic heart failure particularly as intensive care medicine. Sacubitril-Valsartan demonstrated significant effects in improving left ventricular performance and remodeling in patients with heart failure with reduced ejection fraction. Sacubitril acts on increased levels of circulating natriuretic peptides by preventing their enzymatic breakdown and Valsartan, which acts to lessen the effects of the RAAS. However, not more research has been done on its effects on the right ventricle remodeling. This review aimed to assess the impact of angiotensin receptor neprilysin inhibitors on left and right ventricular remodeling in heart failure patients.

Efficacy of Guideline-Directed Medical Therapy in Heart Failure Patients With and Without Chronic Kidney Disease: A Meta-Analysis of 63,677 Patients.

BACKGROUND: Chronic kidney disease (CKD) coexists in up to 50% of heart failure (HF) patients, affecting both those with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF). Although the efficacy of several guideline-directed medical therapies (GDMT) has been well established, the treatment recommendations are similar for those patients with HF with and without CKD. We aimed to investigate the efficacy of GDMT in patients with HF with versus those without CKD. METHOD: This systematic review and meta-analysis included randomised controlled trials that compared the efficacy of GDMT (angiotensin-converting enzyme inhibitor [ACE-I], beta blocker, sodium-glucose cotransporter-2 inhibitor, mineralocorticoid receptor antagonist, angiotensin receptor-neprilysin inhibitor) in patients with HF with and without CKD. The primary outcome was the composite of cardiovascular death and HF hospitalisation. Risk ratios (RR) were pooled using random-effects meta-analysis. RESULTS: A total of 19 trials (15 trials in HFrEF and four trials in HFpEF) enrolling 63,677 (38% had CKD) participants were included. Among HFrEF patients, GDMT reduced the primary endpoint in those with CKD (RR 0.77, 95% confidence interval [CI] 0.72-0.82) and without CKD (RR 0.79, 95% CI 0.74-0.84). Among HFpEF patients, the pooled summary RR for GDMT reducing the primary endpoint was 0.82 (95% CI 0.74-0.91) among those with CKD and 0.88 (95% CI 0.77-0.99) among those without CKD. There was no significant difference in the efficacy of GDMT in head-to-head comparisons between those with and without CKD in HFrEF (ratio of RR 0.97, 95% CI 0.88-1.06) and HFpEF (ratio of RR 0.94, 95% CI 0.80-1.11). CONCLUSIONS: Among patients with HF, GDMT had a consistent effect in reducing adverse cardiovascular events in those with and without CKD. Future studies should investigate the best strategy to ensure patients with HF with CKD receive and tolerate GDMT when indicated.

Knowledge domain and emerging trends in sacubitril/valsartan study from 2008 to 2023 - a visualized conclusive analysis based on novel scientometric tools.

OBJECTIVE: This study aimed to determine the evolution of sacubitril-valsartan research and analyze the publications quantitatively and qualitatively. MATERIALS AND METHODS: We used the bibliometric method and a combination of CiteSpace_6.1.6 and VOSviewer_1.6.18 to identify top authors, countries, institutions, co-cited articles, co-cited journals, keywords, and trends. This study prioritized key aspects in the existing global research on Entresto (Sacubitril/Valsartan) to assess our depth of knowledge in this field and identify potential insights. The objective was to generate a reference for the utilization of the "angiotensin receptor-neprilysin inhibitor" (ARNI). RESULTS: From 2008 to 2022, citations of sacubitril-valsartan showed an upward trend. VOSviewer keyword analysis of 3,408 publications identified 624 keywords and divided them into seven different clusters. The clustered network was constructed based on 1,191 references cited by 3,408 publications that met the terms, where the clustered network of sacubitril-valsartan was presented. These publications can be regarded as fundamental to Entresto's research. Analysis of co-cited reference clusters showed that other than Entresto's novel application in other diseases, the new combination with other medication or mechanical assistance therapies against heart failure was Entresto's latest focus. Analysis of citation bursts showed that the rank of the top 25 keywords, according to the chronological sequence, marked Entresto's research entering a new era of exploring the extended application in other diseases and novel combinations with other diverse therapies. CONCLUSIONS: We found that emerging new mechanisms in sacubitril-valsartan therapy intended for more targets in the pathogenesis of specific diseases will be the focus of further studies.

Management of Hypertension in the Asia-Pacific Region: A Structured Review.

This article reviews available evidence regarding hypertension management in the Asia-Pacific region, focussing on five research questions that deal with specific aspects: blood pressure (BP) control, guideline recommendations, role of renin-angiotensin-aldosterone system (RAAS) inhibitors in clinical practice, pharmacological management and real-world adherence to guideline recommendations. A PubMed search identified 2537 articles, of which 94 were considered relevant. Compared with Europeans, Asians have higher systolic/diastolic/mean arterial BP, with a stronger association between BP and stroke. Calcium channel blockers are the most-commonly prescribed monotherapy in Asia, with significant variability between countries in the rates of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin-receptor blockers (ARBs) and single-pill combination (SPC) use. In clinical practice, ARBs are used more commonly than ACEis, despite the absence of recommendation from guidelines and clinical evidence supporting the use of one class of drug over the other. Ideally, antihypertensive treatment should be tailored to the individual patient, but currently there are limited data on the characteristics of hypertension in Asia-Pacific individuals. Large outcome studies assessing RAAS inhibitor efficacy and safety in multi-national Asian populations are lacking. Among treated patients, BP control rates were ~ 35 to 40%; BP control in Asia-Pacific is suboptimal, and disproportionately so compared with Western nations. Strategies to improve the management of hypertension include wider access/availability of affordable treatments, particularly SPCs (which improve adherence), effective public health screening programs targeting patients to drive health-seeking behaviours, an increase in physician/patient awareness and early implementation of lifestyle changes. A unified Asia-Pacific guideline on hypertension management with pragmatic recommendations, particularly in resource-limited settings, is essential.

Angiotensin Receptor-Neprilysin Inhibition (Sacubitril/Valsartan) Reduces Structural Arterial Stiffness in Middle-Aged Mice.

BACKGROUND: Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age-related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age-related arterial fibrotic remodeling and stiffening in 1-year-old mice. METHODS AND RESULTS: Treatment of in 1-year-old mice with ARNI (sacubitril/valsartan), in contrast to angiotensin receptor blocker monotherapy (valsartan) and vehicle treatment (controls), significantly decreases structural aortic stiffness (as measured by in vivo pulse-wave velocity and ex vivo aortic pressure myography). This phenomenon appears, at least partly, independent of (indirect) blood pressure effects and may be related to a direct antifibrotic interference with aortic smooth muscle cell collagen production. Furthermore, we find aortic remodeling and destiffening due to ARNI treatment to be associated with improved parameters of cardiac diastolic function in aged mice. CONCLUSIONS: This study provides preclinical mechanistic evidence indicating that ARNI-based interventions may counteract age-related arterial stiffening and may therefore be further investigated as a promising strategy to improve cardiovascular outcomes in the elderly.