Blockers In Patients Research Articles

Safety of Calcium Channel Blockers in Patients With Severe Aortic Stenosis and Hypertension.

There is a paucity of data on safety of calcium channel blockers (CCB) in patients with severe aortic stenosis (AS) and hypertension. Among 2,460 patients with severe AS and hypertension receiving antihypertensive therapy in the CURRENT AS registry-2, we compared the clinical outcomes between patients taking antihypertensive therapy with CCB (CCB group) and without CCB (no CCB group). In the entire study population, CCB was prescribed in 1,763 patients (71.7%), which was the most commonly prescribed antihypertensive agents. The prescription rates of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and thiazides were 61.9%, 25.6%, and 7.3% in the CCB group, and 75.8%, 54.4%, and 6.0% in the no CCB group. In the propensity score matched cohort, the cumulative 3-year incidence of all-cause death or hospitalization for heart failure was not different between the CCB and no CCB groups (38.3% vs. 38.7%, log-rank P=0.65; HR, 0.94; 95%CI, 0.77-1.15; P=0.56). The cumulative 3-year incidence of syncope was low regardless of CCB prescription (1.1% vs. 1.0%, P=0.74). Among patients with severe AS and hypertension, CCB was the most commonly prescribed antihypertensive agents, and antihypertensive therapy with CCB was associated with comparable clinical outcomes to antihypertensive therapy without CCB. Syncope was rarely seen in patients with severe AS and hypertension receiving antihypertensive therapy regardless of CCB prescription.

The survival rate of biological therapy in immunosuppressive diseases in children

Genetically engineered biological preparations (GEBP) are successfully used in various immunosuppressive diseases. Despite the effectiveness of GEBP, some patients experience primary non-response, as well as loss of effect from therapy. There is a need to objectively assess the effect of the therapy for its timely correction. The aim of the work was to determine the survival rate of GIBP depending on the form of pathology, drug, age, and immune indices in children with Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS), multiple sclerosis (MS). Materials and methods. Three hundred eighty three children (1394 observations) were examined in dynamics: 117 children with BC (treated by infliximab (IFX)/adalimumab (ADA), 83 children with UC (IFX/ADA), 87 children with PS (ADA), 96 children with PC (IFNβ1α) during the maintenance course therapy. Lymphocytes were immunophenotyped by flow cytometry with the determination of Treg (CD4+CD25highCD127low), Th17 lymphocytes (CD4+CD161+CD3+), succinate dehydrogenase (SDH) activity in Treg. Data processing was carried out using Statistica 16.0 application. Kaplan–Mayer survival curves are constructed. The significance of the differences between the groups was assessed using the Gehan–Wilcoxon criterion (p < 0.05). Results. The survival rate of biological therapy in CD patients on IFX therapy is significantly higher than in children with UC — 161 weeks versus 135 weeks. There was no difference in CBT on ADA therapy between patients with CD and UC. The IBT index depends on the age of the patients: on IFX therapy (159 weeks) the best indices were in CD patients over 12 years. Combination therapy improves the survival of TNF blockers in patients with IBD (azathioprine) and PS (methotrexate). The survival of GIBP is influenced by the ratio of effector and regulatory cells (Th17|Treg) and the functional activity of Treg (SDH activity). A decrease in IBD was revealed in patients with IBD, PS, and MS with an increase in the Th17/Treg index above the age norm and a decrease in the activity of SDH in Treg below the norm. Conclusion. The survival rate of biological therapy for immunosuppressive diseases in children depends on the form of pathology, the drug, the age of patients, previous therapy, combination therapy, as well as immune indices during the maintenance course. Monitoring of Th17/Treg and SDH activity in Treg may be an important laboratory criterion for the effectiveness of GIBP.

Diagnosis and management of hypertrophic cardiomyopathy: European vs. American guidelines.

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, affecting 1:200 to 1:500 individuals worldwide. Guidelines on the diagnosis and management of HCM have been recently published by the European Society of Cardiology (ESC) and American societies. The ESC guidelines cover a broad range of cardiomyopathies, including HCM, with 119 recommendations, whereas the American guidelines focus exclusively on HCM with 141 specific recommendations. Both guidelines emphasize a comprehensive diagnostic approach, including imaging and genetic testing, but differ in some specific aspects. For example, sudden cardiac death (SCD) risk assessment is a primary point of divergence. The ESC guidelines advocate for the use of a validated Risk-SCD calculator, while the American guidelines rely on specific risk markers for individualized risk evaluation. Management strategies also vary: both guidelines prioritize beta-blockers and calcium channel blockers in patients with resting or provocable left ventricular outflow tract (LVOT) obstruction. If beta-blockers (or verapamil/diltiazem) are ineffective, either disopyramide or the myosin inhibitor mavacamten may be an option with slightly different indications among the two guidelines. Septal reduction therapy is recommended in ESC guidelines for symptomatic patients with significant LVOT gradients, while American guidelines suggest earlier myectomy for certain clinical factors and emphasize shared decision-making. The ESC guidelines recommend sequential atrioventricular pacing and dual-chamber defibrillators for reducing LVOT gradients. The American guidelines focus on genetic testing for risk assessment and suggest periodic cardiac magnetic resonance imaging. This paper provides a detailed comparison of these guidelines, highlighting key differences and areas needing further research and expert debate.

Efficacy of beta blockers in patients with thoracic aortic aneurysm: meta-analysis of randomized controlled trials

Abstract Studies investigating the efficacy of β-blocker agents on patients with thoracic aortic aneurysm have produced heterogeneous and conflicting results. This study was aimed to assess protective effects of β-blockers in terms of aortic events (dissection, rupture) and mortality in patients with thoracic aortic aneurysm. A systematic literature search was performed through Ovid MEDLINE, EMBASE, Web of Science, Pubmed and The Cochrane Central Register of Controlled Trials (Cochrane CENTRAL), all from inception to May 10, 2022. Randomized controlled trials exploring the efficacy of β-blocker agents in patients with thoracic aortic aneurysm were considered for inclusion with no population restriction. Two independent reviewers performed the literature search. Two reviewers independently extracted all available prespecified relevant data in accordance with the International Prospective Register of Systematic Reviews protocol. Summary effect measures of the primary outcomes were obtained by pooling the data with an inverse variance–weighted random-effects model. The overall risk of bias assessment was conducted by using the Cochrane Risk of Bias 2 tool A sensitivity analysis was performed regarding whether the conclusions reached might differ substantially if a single study was omitted. The primary outcome was aortic events (aortic dissection/rupture). Secondary outcomes were death (all-cause mortality) and aortic dissection. Two independent reviewers identified 4 RCTs presented in 5 reports from 1494 unique studies screened. Three trials involving 129 eligible participants compared β blockers (propranolol and celiprolol) with no treatment. One trial involving 32 eligible participants compared β blocker (atenolol) with placebo. This systematic review and meta-analysis included 161 patients with thoracic aortic aneurysm (mean age, 27.6 years; 80 [49.7%] male, mean follow-up 6.7 years). The pooled risk ratio in the β-blocker arm for aortic events was 0.74 [95% CI (0.20; 2.71), I2: 0%, p=0.64] when comparing to the placebo or no treatment in patients with thoracic aortic aneurysm. The pooled risk ratio for death (all-cause mortality) and aortic dissection in the β-blocker arm were 0.45 [95% CI (0.10; 1.98), I2: 0%, p=0.29] and 0.58 [95% CI (0.15; 2.24), I2: 0%, p=0.43], respectively. The risk of aortic dissection, rupture, or death were essentially identical, regardless of treatment group and subgroup analysis. A sensitivity analysis revealed that none of the studies significantly influenced the pooled risk estimate to any great extent. We found no evidence of benefit from β-blocker treatment. More robust data regarding β-blocker use in patients with thoracic aortic aneurysms from randomized controlled trials are needed to establish evidence based recommendations and to determine whether current evidence comes from absense of evidence or evidence of absense.Forest plot for death (all-cause)

Prescription Pattern of Beta Blockers in Patients Diagnosed with Heart Failure

This study will be helpful to detect the dosage, frequency and duration of beta blockers which is prescribed for heart failure patients that is followed the guideline. The goal of the study was to describe the prescription pattern of beta blockers in patients diagnosed with heart failure. Hypothyroidism, hypertension, type 2 diabetes mellitus patients are very prone to get Heart failure. Beta blockers should be prescribed, respective with the symptoms that occurred specifically to a particular patient. This study helped to detect the parameters of prescribing beta blockers in different symptoms and co morbidities. A Total of 39 patients, among them It was observed that (46.05%) patients having heart failure were from age group 48-57, followed by (2.5%) of 78-87 age group, of which the males (58.96%) proportion where seems more than the females (41.04%). The prescription pattern for heart failure patients were found as 100% Beta adrenergic blockers, such as metoprolol-65%, bisoprolol-22%, Carvedilol-15% were given. It is evident that the beta blockers are mainly prescribed according to the symptoms, carvedilol exhibits a more pronounced BP lowering effect as a consequence of its α1- receptor blocking activities and thus causes more frequent dizziness and hypotension. In patients predisposed to symptomatic hypotension, metoprolol succinate may be the more desirable whereas in patients with uncontrolled hypertension, carvedilol may be preferred. A selective β1-blocker such as metoprolol succinate is a reasonable option for patients with reactive airway disease.

Effects of calcium channel blockers in patients with heart failure with preserved ejection fraction: A protocol for systematic review and meta-analysis.

Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance. Due to the frequent coexistence of hypertension in HFpEF patients, the use of anti-hypertensive medications is common in their treatment. While many cohort studies and several randomized controlled trials (RCTs) have examined the effectiveness of various anti-hypertensive drugs such as beta-blockers and renin-angiotensin system inhibitors in HFpEF, the role of calcium channel blockers (CCBs) remains uncertain. Despite several RCTs and cohort studies exploring the effects of CCBs on prognosis and exercise capacity in HFpEF patients, the findings have been inconsistent, likely due to limited statistical power and/or variations in study design. Therefore, our aim is to conduct a systematic review and meta-analysis of studies on the effects of CCBs in these patients. This meta-analysis will include RCTs and cohort studies on the effect of CCBs in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome of interest will be prognosis. The secondary outcome of interest will be exercise capacity. Synthesizing our meta-analytical results with expert consensus could contribute to the formulation of updated clinical guidelines. Our systematic review and meta-analysis will provide directions for future research on the use of CCBs in HFpEF patients. INPLASY202430097.

Sex-based differences in left ventricular mass reduction across angiotensin II receptor blockers in patients with heart failure with preserved or mildly reduced ejection fraction.

Although angiotensin II receptor blockers (ARBs) are more effective in women for either reduction of blood pressure or heart failure (HF), the gender disparities and the impact of class/drug effects on ARBs in relation to cardiac hypertrophy and HF remain unclear. We aimed to investigate the sex-based and drug-specific differences in left ventricular (LV) mass reduction with ARBs. We employed the cohort of 193 hypertensive patients with HF and an LV ejection fraction of ≥ 45% treated with azilsartan or candesartan once daily for 48 weeks as a sub-analysis of the J-TASTE trial. After exclusion of patients without LV mass data nor the drugs, 170 patients were finally enrolled (azilsartan: male, n = 43, female, n = 39 and candesartan: male, n = 52; female, n = 36). We investigated the sex-based differences of the primary endpoint of the change in LV mass as assessed by echocardiography from baseline to the end of the study (48 weeks), and the secondary endpoint of the incidence of the composite cardiovascular endpoint (death from cardiovascular disease or hospitalization for heart failure). In the male stratum, the ratio of patients with > 10% LV mass reduction at 48 weeks was higher in the azilsartan group than candesartan group (40 vs. 19%, p = 0.029). There was no significant difference in LV mass reduction between two groups in the female stratum. There were no differences of the onset of the secondary endpoints between male and female groups, and azilsartan and candesartan groups. The event-free survival rate of the composite cardiovascular endpoints tended to be lower in patients with ≤ 10% than > 10% LV mass reduction (95.3 vs. 100% at 48 weeks, log-rank p = 0.11). In patients with HF, the effectiveness of either azilsartan or candesartan in achieving > 10% LV mass reduction depends on sex. Male is more sensitive to azilsartan than candesartan to achieve cardiac hypertrophy in HF patients.

β-Adrenoceptor blockade can augment the torsadogenic action of risperidone

Risperidone is a second-generation antipsychotic for treating schizophrenia and bipolar disorder. It can potently inhibit IKr, but is classified into conditional risk for torsade de pointes (TdP) by CredibleMeds®. Our previous studies using chronic atrioventricular block dogs showed that risperidone alone did not induce TdP, and that dl-sotalol (β-adrenoceptor blockade plus IKr inhibition) induced TdP three times more frequently than d-sotalol (IKr inhibition alone). Since risperidone can block α1-adrenoceptor and decrease blood pressure, the resulting reflex-mediated increase of sympathetic tone on β-adrenoceptor might protect the heart from its IKr inhibition-associated TdP. To validate this hypothesis, risperidone was administered to chronic atrioventricular block dogs after β-adrenoceptor blocker atenolol infusion with monitoring J-Tpeak and Tpeak-Tend, which are proarrhythmic surrogate markers of "substrate" and "trigger" toward TdP, respectively. Atenolol alone induced TdP in 1 out of 5 dogs; moreover, an additional infusion of risperidone induced TdP in 3 out of 4 dogs. Risperidone prolonged QT interval, J-Tpeak and Tpeak-Tend in animals that induced TdP. These findings indicate that β-adrenoceptor blockade can diminish repolarization reserve to augment risperidone’s torsadogenic potential, thus advising caution when using β-adrenoceptor blockers in patients with IKr inhibition-linked labile repolarization.

Effect of Cholinergic Receptor Antagonists on the Potentiation of the Effect of Adenosine Receptor Blockers in People with Bronchial Asthma

Background: The interaction between adenosine receptor blockers and anticholinergic substances in the treatment of bronchial asthma is an area of interest. The efficacy of such combinations in managing bronchial asthma and bronchial hypersensitivity needs to be explored further. Understanding lung function parameters such as airway resistance and intrathoracic gas volume is crucial for evaluating the effects of these medications. Objective: This study aimed to investigate the effect of combining the adenosine receptor blocker, bamifylline, with the anticholinergic substance, ipratropium bromide spray, in patients with bronchial asthma. Specifically, the study sought to assess changes in lung function parameters, including airway resistance and intrathoracic gas volume, after administering ipratropium bromide alone and in combination with bamifylline. Methods: Sixteen patients with bronchial asthma were enrolled in the study. Lung function was evaluated using body plethysmography, with measurements of airway resistance (Raw), intrathoracic gas volume (ITGV), airway specific resistance (SRaw), and airway specific conductance (SGaw). Patients initially received ipratropium bromide inhalation (2 inhalations x 20µg), followed by Raw and ITGV measurements at intervals (5, 30, 60, and 120 minutes). Subsequently, patients received bamifylline (2 x 600 mg) daily for seven days at home. On the eighth day, they were administered ipratropium bromide spray (2 inhalations x 20µg), and lung function parameters were assessed similarly. Results: Administration of ipratropium bromide alone led to a significant reduction in airway resistance (p<0.05). However, the combination of ipratropium bromide with bamifylline did not significantly enhance the effects of adenosine receptor blockade (p<0.05). Specifically, there were no significant changes in Raw, ITGV, SRaw, or SGaw after combining ipratropium bromide with bamifylline. Conclusion: The study findings suggest that the addition of anticholinergic substances did not potentiate the action of adenosine receptor blockers in patients with bronchial asthma. Therefore, the anti-inflammatory effects of xanthines, such as bamifylline, were not augmented by anticholinergic substances in this study. These results highlight the need for further research to explore alternative therapeutic approaches in the management of bronchial asthma.

Evaluating prescription of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in patients with diabetes and albuminuria.

Although guidelines recommend the use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) in patients with diabetes, hypertension, and albuminuria, their use remains suboptimal in several developed countries. Limited data are available on ACEi/ARB use in developing countries. Here, we assessed the use of ACEi/ARB and identified factors contributing to their underutilization at Hatyai Hospital, Thailand. This retrospective cross-sectional study was conducted using data from the Hatyai Hospital database. Adult patients with diabetes, hypertension, and albuminuria were included. Clinical data and laboratory results were extracted. Furthermore, this study recorded pre-specified conditions that influenced physicians' decisions regarding the prescription of ACEi/ARBs in patients who did not adhere to guidelines. Of 4,655 eligible patients, 500 patients were selected. The average age of the patients was 66.3 years, and 59.6% were female. The adherence rate was 72.4%. Multivariate logistic regression analysis found a significant association between non-adherence and chronic kidney disease (CKD) stage (OR = 1.29, 95% CI: 1.04-1.60, p = 0.019). The most common pre-specified condition contributing to non-adherence was "no condition identified" (69.8%). Among the cases of non-adherence, 21.7% were due to ACEi/ARB discontinuation after acute kidney injury, followed by hyperkalemia (5.1%) and a moderate increase in serum creatinine (4.3%). ACEi/ARB therapy was suboptimal in patients with diabetes, hypertension, and albuminuria. Non-adherence was associated with CKD stage, possibly because of concerns about adverse events and healthcare-related factors.

Comparison between beta-blockers and calcium channel blockers in patients with atrial fibrillation according to renal function.

Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR). The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m2, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026). In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation.

Calcium channel blockers in patients with pulmonary arterial hypertension receiving PAH-specific treatment

BackgroundCalcium channel blockers (CCB) are the first effective therapy for vasoreactive patients with idiopathic pulmonary arterial hypertension (IPAH). However, the advent of modern PAH-specific drugs may undermine the role of vasoreactivity tests and CCB treatment. We aimed to clarify the effect of acute vasoreactivity testing and CCB on patients with IPAH receiving PAH-specific treatment. MethodsWe retrospectively investigated consecutive patients with IPAH (n = 136) diagnosed between 2000 and 2020 and collected data from patients who underwent acute vasoreactivity testing using inhaled nitric oxide (NO). The effects of vasoreactivity testing and CCB therapy were reviewed. Long-term survival was analysed using the Kaplan–Meier method. ResultsAcute vasoreactivity testing was performed in 49% of patients with IPAH (n = 67), including 23 patients (34%) receiving PAH-specific therapy without vasoreactivity testing. Eight patients (12%), including three patients (4.4%) receiving PAH-specific therapy, presented acute responses at vasoreactivity testing. They received high-dose CCB therapy (CCB monotherapy for five patients [7.5%] and CCB therapy and PAH-specific therapy for three patients [4.4%]). They presented a significant improvement in clinical parameters and near-normalisation of haemodynamics (mean pulmonary arterial pressure decreased from 46 [interquartile range: 40–49] to 19.5 [interquartile range: 18–23] mmHg [P < .001] at 1-year follow-up). All eight vasoreactive responders receiving CCB therapy showed better long-term survival than non-responders treated with PAH-specific therapy (P < .001). ConclusionsCCB therapy benefited patients with IPAH who showed acute response to vasoreactivity testing using inhaled NO, even when receiving modern PAH-specific therapy. Acute vasoreactive responders may benefit more from CCB than from PAH-specific therapy.

Beta Blockers in Contemporary Cardiology: Is It Better to Cast Them Out?

Beta blockers are one of the commonest prescription drugs in medicine and they have been thought to revolutionize the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) in the last century. In addition to HFrEF, they are prescribed for a variety of diseases in cardiology from hypertension to HF, angina, and stable coronary artery disease (CAD). The increased prescription of beta blockers in conditions like HF with preserved ejection fraction (HFpEF), and stable CAD may be doing more harm than good as per the data we have so far. The available data shows that beta blockers are associated with increased stroke risk and atrial fibrillation (AF) in hypertension and in patients with HFpEF, they have been associated with decreased exercise capacity. In patients with stable CAD and patients with myocardial infarction with normal systolic functions, beta blockers don't offer any mortality benefit. In this article, we critically review the common indications and the uses of beta blockers in patients with HFpEF, CAD, hypertension and AF and we propose that beta blockers are over-prescribed under the shadow of their beneficial effects in patients with HFrEF.

Assessment of physician compliance to the CAEP 2021 Atrial Fibrillation Best Practices Checklist for rate and rhythm control in the emergency department.

Acute atrial fibrillation and flutter (AF/AFL) are common arrhythmias treated in the emergency department (ED). The 2021 CAEP Best Practices Checklist provides clear recommendations for management of patients with acute AF/AFL. This study aimed to evaluate physician compliance to Checklist recommendations for risk assessment and ED management of AF/AFL. This health records review assessed the management of adult patients presenting to two tertiary care EDs for management of acute AF/AFL from January to August, 2022. All ECGs demonstrating AF/AFL with a heart rate greater than 100 were compiled to capture primary and secondary causes. All visits were assessed for rate and rhythm control management, adverse events, return to ED, and safety criteria. Study physicians classified safety criteria from the Checklist into high and moderate concerns. The primary outcome was the proportion of cases with safety concerns and adverse events occurring during management in the ED. Data were analyzed using simple descriptive statistics. We included 429 patients with a mean age of 67.7years and 57.1% male. ED management included rate control (20.4%), electrical (40.1%), and pharmacological (20.1%) cardioversion. Adverse events occurred in 9.5% of cases: 12.5% in rate control, 13.4% in electrical cardioversion, and 6.9% in pharmacologic cardioversion. Overall, 7.9% of cases had management safety concerns. Moderate safety concerns occurred in 4.9% of cases including failure to attain recommended heart rate at time of discharge (3.9%). Severe concerns were identified in 3.0% of cases including failure to cardiovert unstable patients (1.2%). The 30-day return-to-ED rate was 16.5% secondary to AF/AFL. ED management of AF/AFL was consistent with the CAEP Checklist and was safe overall. Opportunities for optimizing care include attaining recommended targets during rate control, avoidance of calcium channel and beta blockers in patients with systolic dysfunction, and earlier cardioversion for clinically unstable patients.

Comparative effectiveness of sacubitril/valsartan versus angiotensin receptor blockers in patients with heart failure with preserved ejection fraction: A real-world study.

Sacubitril/valsartan (SAC/VAL) or angiotensin receptor blockers (ARBs) are recommended therapy for heart failure with preserved ejection fraction (HFpEF), but little is known about their real-world comparative effectiveness among patients with HFpEF. The objective of this study was to determine the comparative effectiveness of SAC/VAL vs ARBs in preventing HF-related hospitalization or all-cause hospitalization among patients with HFpEF. We conducted a cohort study using IBM MarketScan commercial and Medicare supplemental databases to identify patients aged 18 years or older with a diagnosis of HFpEF and initiation of SAC/VAL (2015-2020) or ARB (2009-2014) therapy. The index date was the date of the first SAC/VAL or ARB prescription fill. After propensity score (PS) matching with a ratio of 1 up to 3, Cox proportional hazards regression was used with robust variance estimators to compare the risks of HF-related hospitalization and all-cause hospitalization between the 2 therapies. Several subgroup and sensitivity analyses were conducted to check the robustness of the main analysis. After PS matching, 2,520 patients (846 receiving SAC/VAL and 1,674 receiving an ARB) were included in the final analyses. After controlling for covariates, there was no difference in the risk of HF-related hospitalization between SAC/VAL and ARB recipients (adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 0.99-1.77). There was also no difference in the risk of all-cause hospitalization between SAC/VAL and ARB recipients (aHR, 1.06; 95% CI, 0.91-1.24). Among individuals with private or Medicare Advantage insurance plans, there was no significant difference in the risk of HF-related hospitalization or all-cause hospitalization between adults with HFpEF who received SAC/VAL and those who received ARB therapy.

Retirada del tratamiento farmacológico en pacientes respondedores a terapia de resincronización cardiaca: justificación y diseño del ensayo clínico REMOVE

Introduction and objectivesCardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. MethodsThe REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. ConclusionsThe results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).

Comparison of the Efficacy and Safety of Sacubitril/Valsartan and Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Patients With Reduced Ejection Fraction Combined With Moderate-to-Severe Chronic Kidney Disease.

Background and Objectives: The efficacy and safety of a lower target dose of sacubitril/valsartan (angiotensin receptor neprilysin inhibitor [ARNI]) for treating heart failure with reduced ejection fraction (HFrEF) in Chinese patients with moderate-to-severe chronic kidney disease (CKD) remain unknown. We performed a retrospective study to compare the efficacy of ARNI with that of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) in patients with HFrEF and moderate-to-severe CKD. Methods: This retrospective study included 129 patients. An inverse probability of treatment weighting (IPTW) analysis was performed to compare the baseline characteristics and outcomes between the 2 groups. The incidence of death due to cardiovascular disease, rehospitalization due to heart failure after treatment, and improvement in cardiac function symptoms (New York Heart Association [NYHA]) were assessed after 12 months. Improvements of ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) level, left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD) were compared. Results: Compared with the ACEI/ARB group, the ARNI group, with 90.77% (59/65) in the lower target dose group, showed a lower rate of death due to cardiovascular disease (6.6% vs 0.9% after IPTW) and a lower incidence of rehospitalization (46.5% vs 30.4% after IPTW). NYHA class, estimated glomerular filtration rate, EF, NT-ProBNP levels, LVEDD, and LVESD improved in the ARNI group. None of the patients withdrew from treatment because of adverse drug reactions. Conclusion: Our study showed that ARNI resulted in a greater improvement in heart failure than ACEIs/ARBs in patients with HFrEF and moderate-to-severe CKD.

Genetic Diagnosis in Neonatal Encephalopathy With Hypoxic Brain Damage Using Targeted Gene Panel Sequencing.

Neonatal encephalopathy (NE) is a neurological syndrome that presents with severe neurological impairments and complications. Hypoxic-ischemic encephalopathy is a major contributor to poor outcomes, being responsible for 50%-80% of admissions to neonatal intensive care units. However, some cases of NE accompanied by hypoxic brain damage cannot be solely attributed to hypoxia-ischemia. We aimed to identify diverse pathogenic genetic variations that may be associated with cases of NE accompanied by hypoxic brain damage rather than hypoxia-ischemia. We collected data from 34 patients diagnosed with NE accompanied by hypoxic brain damage over a 10-year period. Patients with the following specific conditions were excluded: 1) premature birth (<32 weeks), 2) no history of hypoxic events, 3) related anomalies, 4) neonatal infections, 5) antenatal or perinatal obstetrical complications, 6) severe hypoxia due to other medical conditions, and 7) early death (within 1 week). A comprehensive review of clinical and radiological features was conducted. A genetic diagnosis was made in 11 (32.4%) patients, with pathogenic variants being identified in the following 9 genes: CACNA1A (n=2), KCNQ2 (n=2), SCN2A (n=1), SCN8A (n=1), STXBP1 (n=1), NSD1 (n=1), PURA (n=1), ZBTB20 (n=1), and ENG (n=1). No specific treatment outcomes or clinical features other than preterm birth were associated with the results of the genetic analyses. Personalized treatments based on the results of genetic tests were attempted, such as the administration of sodium-channel blockers in patients with KCNQ2 or SCN8A variants and the implementation of a ketogenic diet in patients with STXBP1 or SCN2A mutations, which demonstrated some degree of effectiveness in these patients. Genetic analyses may help in diagnosing the underlying etiology of NE and concurrent hypoxic brain damage, irrespective of the initial clinical features.

Effects of Nebivolol therapy on hemodynamic parameters and lipid profile compared to other beta blockers in patients with essential hypertension: a systematic review and meta-analysis.

Besides being commonly used to treat high blood pressure, beta blockers are a family of drugs that are primarily used to regulate irregular cardiac rhythms. Nebivolol is a third generation of beta blockers, which is highly cardioselective, about three times as selective as bisoprolol. In this study, we aimed to evaluate Nebivolol's effectiveness and safety in comparison to other beta blockers. We searched the online databases PubMed, ScienceDirect, and Cochrane Library for relevant RCTs evaluating Nebivolol's effect on hypertension management. Relative risk (WRR) and weighted mean difference (WMD), with a 95% confidence interval (CI) were utilized to quantify the impact of nebivolol medication in the treatment of hypertension using a random effects model. Twelve RCTs are included in the study, the patient numbers in every attempt ranged from 42-273 and 1456 patients in all were included in this review. Nebivolol does not significantly reduce SBP, DBP and HR compared to other beta blockers (WMD -0.57 mmHg, 95% CI [-1.55; 0.42 mmHg] p=0.12; WMD -0.27 mmHg, 95% CI [-1.36; 0.82 mmHg] p=0.63 ; WMD 0.10 BPM, 95% CI [-4.11;1.31 BPM] p=0.96, respectively). Patients treated with Nebivolol has significantly lower LDL-C (WMD -8.88 mg/dL, 95% CI [-15.28; -2.48 mg/dL] p=0.007) and significantly higher HDL-C (WMD 2.30 mg/dL, 95% CI [0.75; 3.84 mg/dL] p=0.004. According to this study's findings, nebivolol is well tolerated and decreases LDL-C. And higher HDL-C than other beta blocker agents. This review does not recommend nebivolol as first-line treatment in hypertension as Nebivolol does not significantly reduce blood pressure and HR of patients.

Beta-blockers in chronic heart failure with preserved left ventricular ejection fraction: is deprescribing possible?

Chronic heart failure (CHF) is a complex clinical syndrome characterized by poor prognosis. According to the Russian epidemiological study EPOHA-CHF, more than half of patients with CHF have preserved left ventricular ejection fraction (LV EF). However, no class of drugs has proven effectiveness in improving the prognosis of this disease. Although current clinical guidelines do not recommend the routine use of beta-blockers in CHF patients with preserved LV EF in the absence of other indications for them, many patients with CHF with preserved LV EF take these drugs unreasonably. The review presents the data from studies on the efficacy and safety of betablockers in CHF with preserved LV EF and it withdrawal. Most studies included patient with LV EF &gt;40%, a few of them analyzed only patients with LVEF ≥50%. Some studies of real clinical practice and meta-analysis of such studies demonstrated a positive effect of beta blockers in patients with LV EF &gt; 40%, however randomized clinical trials and their meta-analyses revealed either a slight beneficial effect of beta-blockers. Studies involving only patients with LV EF ≥50% didn’t show the beneficial effects of beta blockers. There is only one trial accessing the withdrawal of beta blockers in patients with CHF with preserved LV EF and chronotropic insufficiency. The study showed a positive effect of deprescribing on exercise tolerance and quality of life. Due to controversial data, well-designed trials to examine the effect of beta-blockers on symptoms and prognosis in patients with CHF with LVEF ≥50% are required. Deprescribing of beta-blockers also require further assessment.