Use Of Β-blockers Research Articles

Effects of β-blockers on the Outcomes in Patients with Pulmonary Arterial Hypertension Stratified by the Presence of Comorbid Conditions: a Multicenter Prospective Cohort Study (BNP-PL)

The current guidelines do not recommend β-blockers in pulmonary arterial hypertension (PAH) unless indicated by comorbidities. However, the evidence regarding the role of β-blockers in PAH is contradictory. What are the effects of β-blockers on clinical outcomes in patients newly diagnosed with pulmonary arterial hypertension (PAH), and how do these outcomes differ based on the presence of cardiovascular comorbidities that are standard indications for β-blocker use? We analyzed data from 806 patients newly diagnosed with PAH enrolled prospectively in the Database of Pulmonary Hypertension in the Polish Population (BNP-PL). The endpoints were all-cause mortality and a composite of hospitalization due to right heart failure, syncope or death. Indications for β-blocker included hypertension, significant arrhythmia, and coronary artery disease(CAD). Propensity score matching (PSM) was used to form a control group based on age, PAH mortality risk variables and initially introduced PAH specific therapy. Out of the 806 patients, 469 (58.2%) received β-blockers at the time of PAH diagnosis. In PSM, β-blocker treatment showed a higher incidence of the composite endpoint (HR:1.44; 95% CI: 1.04-1.99; P = .03) and had neutral impact on mortality (HR, 1.22; 95% CI, 0.87-1.72; P = .25). When stratified by the presence of comorbidities, β-blockers showed adverse effects on composite endpoint in patients without comorbidities and a neutral effect in patients with at least one comorbidity INTERPRETATION: β-blockers pose significant risks in patients with PAH, especially in patients without coexisting systemic hypertension, CAD and arrhythmia.

Contemporary use of beta-blockers in the outpatient treatment of heart failure with atrial fibrillation

Abstract Background Evidence of the effectiveness of β-blockers in heart failure (HF) and atrial fibrillation (AF) in a contemporary cohort is controversial. This study investigated the association between the use of β-blockers and prognosis in outpatients across a broad spectrum of HF with AF. Methods Patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between 2014 and 2021. Associations of β-blocker use at discharge and prognosis were compared by propensity score matching among the AF or non-AF group. A multilevel mixed-effects survival model was used with hazard ratio (HR) and 95% confidence interval (CI). Results Among 428,650 patients discharged with HF in 4,433 hospitals, 175,174 (40.9%) were ≥85 years old, 151,873 (35.4%) had complicated AF, and 236,457 (55.2%) were β-blocker users. In a matched AF group, β-blocker use was associated with a lower composite outcome of all-cause mortality or HF rehospitalization (HR [95% CI], 0.95 [0.93–0.97]). A similar result was obtained in a matched non-AF group (0.95 [0.94–0.96]). In addition, the HRs in patients aged ≥85 years and female patients were 1.00 [0.98–1.02] and 1.01 [0.98–1.03] in the AF group and 1.03 [1.01–1.05] and 0.98 [0.97–1.00] in the non-AF group, respectively (Figure). Conclusions The favorable prognostic associations of β-blocker use were observed regardless of AF in outpatients across a broad spectrum of HF in a superaged society. However, β-blocker use may not be effective in older or female patients.

Visit-to-visit changes in heart rate in heart failure: a pooled participant-level analysis of the PARADIGM-HF and PARAGON-HF trials

Abstract Background Resting heart rate (HR) is a strong established marker of risk in patients with heart failure (HF), but the clinical implications of changes in HR over time are less well established. We aimed to explore the association between visit-to-visit changes in HR and cardiovascular (CV) outcomes in a pooled participant-level dataset of 2 large cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF). Methods PARADIGM-HF and PARAGON-HF were global, multicenter, randomized clinical trials testing sacubitril/valsartan against an active control (enalapril or valsartan, respectively) in patients with HF and LVEF ≤40% (in PARADIGM-HF) or LVEF ≥45% (in PARAGON-HF). Change in HR was defined as the difference in HR between a visit at any time and the preceding visit. The association between the change in HR and subsequent risk of first HF hospitalization (HFH) or CV death was assessed using Cox proportional hazards models, after adjusting for HR at the preceding visit and potential confounders. HR at any time was also assessed using repeated measures regression models with restricted cubic splines, and was plotted relative to time defined as the number of months prior to or immediately following a HFH event or end of follow-up. Patients who experienced HFH during the study period were compared to a control population who remained free of all-cause hospitalization and all-cause death during the follow-up period. Results A total of 13,194 patients (mean age 67±11 years, 67% men, mean LVEF 40±15%) were included. Heart rates were available in 16 visits in both PARADIGM-HF and PARAGON-HF. Over a median follow-up of 2.4 years, 3,114 patients underwent a first HFH or CV death (10.4 events per 100 patient-years). Any increase in HR from the preceding visit, compared with no change, was associated with a significantly higher risk of first HFH or CV death (Figure 1, adjusted hazard ratio 1.10, 95% confidence interval, CI: 1.08–1.13, P<0.001, per 5 bpm increase in HR). Conversely, a drop in HR was associated with significantly lower risk. This prognostic association between temporal changes of HR and risk of first HFH or CV death was consistent across the range of LVEF (Pinteraction=0.34) and seen irrespective of background use of β-blockers (Pinteraction=0.91). Relative increases in HR were especially prognostic in patients without a history of atrial fibrillation/flutter (Pinteraction=0.01). HR at any time appeared to increase during the 8 months prior to a HFH event, and remained elevated after hospitalization, in comparison to a relatively stable HR observed in the control group (Figure 2). Conclusions Across a broad spectrum of patients with chronic HF, relative increases in HR from a preceding visit strongly and independently predicted both CV and non-CV outcomes. Our findings suggest that detection of notable increases in HR between outpatient visits may help identify patients at heightened risk of adverse events.

Guideline-directed medical therapy and in-hospital mortality in acute coronary syndrome patients with advanced renal dysfunction

Abstract Background It is unclear whether early (initiated within 24 hours of admission) guideline-directed medical therapy [GDMT, i.e., the combined use of β-blocker, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, dual antiplatelet drugs and statin] could benefit acute coronary syndrome (ACS) patients with advanced renal dysfunction [estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2]. Objectives The purpose of this study was to verify whether GDMT could improve in-hospital mortality in ACS patients with advanced renal dysfunction. Methods This study included 3,288 and 3,520 ACS patients with admission with advanced renal dysfunction from the CNEDSSP and CCC-ACS cohorts, respectively. Multivariable-adjusted analysis and propensity score matching (PSM) were employed to assess the impact of GDMT on in-hospital mortality. Results In a pooled analysis of the CNEDSSP and CCC-ACS cohorts, early GDMT was associated with significantly lower in-hospital mortality (relative ratio [RR]: 0.62, 95% CI: 0.47 to 0.81). PSM revealed an attenuation of the association of in-hospital mortality with early GDMT in ACS patients, with statistically significant associated reductions observed only in myocardial infarction (MI) patients (hazard ratio [HR]: 0.45, 95% CI: 0.27 to 0.75 in CNEDSSP cohort; HR: 0.48, 95% CI: 0.27 to 0.84 in CCC-ACS cohort). A random-effect pooled analysis for MI patients with admission advanced renal dysfunction demonstrated a 56% lower in-hospital mortality among GDMT users (RR: 0.44, 95% CI: 0.31 to 0.65). Conclusions This nationwide study highlights that early GDMT is associated with a reduced risk of in-hospital mortality in ACS patients (particularly in MI patients) with advanced renal dysfunction.

Epidemiology, clinical characterization, and outcomes for heart failure with improved ejection fraction

Abstract Background Contemporary guidelines propose a new classification of heart failure with improved ejection fraction (HFimpEF). The prevalence of HFimpEF is expected to increase with the implementation of guideline-directed medical therapy (GDMT); however, there are limited data on the epidemiology of and outcomes for this novel clinical entity. Purpose We describe the prevalence, GDMT use and outcomes among patients with HFimpEF within a large, integrated healthcare delivery system. Methods We identified adults ≥18 years with incident HF with reduced EF (HFrEF ≤40%) between January 2013 and December 2018 from a large, integrated healthcare system serving >4.5 million members. HFimpEF was defined as known HFrEF with a follow-up EF measurement >40% within 12 months after incident HFrEF. Among HFimpEF patients, we examined GDMT use at discharge after incident HFrEF, incident HFimpEF, and at 6- and 12-months post-HFimpEF. From 12 months post initial HFrEF diagnosis, we calculated incidence rates of subsequent worsening HF (WHF) events (i.e., HF-related hospitalization, emergency department or urgent outpatient visits adjudicated using validated natural language processing-based algorithms) and all-cause death through December 31, 2019. We compared rates between patients with HFimpEF and those with persistent HFrEF (i.e., having all LVEF measurements within 12 months of incident HFrEF ≤40%) using Cox proportional hazards models adjusted for the EF value at incident HFrEF. Results Among 12,639 patients with incident HFrEF, 4,124 (33%) experienced HFimpEF within 12 months. Among patients with HFimpEF, use of β-blockers (82%) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers (86%) was high, while angiotensin receptor-neprilysin inhibitor (1.2%) or mineralocorticoid receptor antagonist (28.2%) use was low. β-blockers, ACEi/ARB, and MRA use declined after incident HFimpEF (Figure, Panel A). Rates of WHF were 19.7 (95% Confidence Interval [CI]: 18.7 to 20.6) per 100 person-years among patients with HFimpEF vs. 40.0 (95% CI: 38.5 to 41.5) among patients with persistent HFrEF (hazard ratio [HR]: 0.55, 95% CI: 0.49 to 0.62; Figure, Panel B). Rates of death were 5.2 (95% CI: 4.7 to 5.7) and 8.4 (95% CI: 7.8 to 9.1) per 100 person-years among HFimpEF and persistent HFrEF, respectively (HR: 0.59, 95% CI: 0.52 to 0.67). Among patients with HFimpEF, those with an absolute EF improvement of ≥20% were less likely to experience WHF (HR: 0.82, 95% CI: 0.67 to 0.99) and death (HR: 0.85, 95% CI: 0.69 to 1.04) compared with those with <20% improvement. Conclusions One in three patients experienced improvement in EF within 12 months of initial HFrEF diagnosis. HFimpEF is associated with a reduced risk of WHF events and death, although these patients remain at significant clinical risk. Further research is necessary to assess the potential impact of sustained adherence to GDMT and therapeutic optimization on HFimpEF patient outcomes.

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)

Temporal trends in sudden cardiac death after acute decompensation in HFrEF patients: a 13-year Japanese multicentre registry study

Abstract Background The implementation of guideline-based medical therapy (GBMT) for heart failure with reduced ejection fraction (HFrEF) has significantly contributed to reducing mortality risks. Yet, detailed analyses on temporal trends of sudden cardiac death (SCD) among these patients, especially post-discharge following acute decompensation, remain scarce. Purpose This study aimed to explore changes in the incidence of SCD over the last 13 years in patients with HFrEF discharged after acute decompensation treatment, and to identify clinical factors associated with SCD risk. Methods We analyzed 2,604 consecutive HFrEF (left ventricular ejection fraction [LVEF] ≤40%) patients enrolled in a Japanese multicentre acute heart failure (HF) registry from 2009 to 2021. SCD was defined as an unexpected and otherwise unexplained death in a previously stable patient or death due to documented or presumed cardiac arrhythmia without a clear non-cardiovascular cause. The determination of death cause (SCD, pump failure death, or other) was made by a central adjudicating committee. The Fine and Gray method was employed to analyze factors associated with SCD. The variables submitted to the model included age (≥70 years), gender, LVEF (<30%), ischaemic aetiology and prescription of GBMT (use of renin-angiotensin system inhibitors, β-blockers and mineralocorticoid receptor antagonist) at discharge. Results The mean age of studied patients was 70.9±14.2 years, and 70.0% were male. During the 1-year follow-up period, 262 deaths (10.1%) occurred, including 51 SCDs (2.0%). Older age was associated with an increased risk of SCD (adjusted hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.40-5.64, P=0.004). Further, patients with an ischaemic aetiology had a higher risk of SCD (HR 1.84, 95% CI 1.06-3.22, P=0.032). During the study period, mean age remained constant (71.0 years to 70.7 years, P for trend =0.884). The proportion of ischaemic aetiology also remained constant (from 37.2% to 38.2%, P for trend =0.972). Overall, there were significant decreases in the incidence of all cause death and SCD (from 13.7% to 8.4%, P for trend =0.002; and from 3.5% to 1.0%, P for trend <0.001; Figure A). Notably, there was an increase in the prescription rate of three classes of GBMT at discharge (from 30.9% to 45.6%, P for trend <0.001; Figure B), and the rate of implantable cardioverter-defibrillator (ICD) use in eligible patients (New York Heart Association functional class II-III with LVEF ≤35%) remained constant (from 9.6% to 11.6%, P for trend =0.157; Figure B). Conclusions With the increasing use of GBMT, the incidence of SCD decreased in real-world patients with HFrEF registered in a Japanese acute HF registry over the past decade.

The sympathetic nervous system in heart failure with preserved ejection fraction.

The sympathetic nervous system (SNS) is a major mediator of cardiovascular physiology during exercise in healthy people. However, its role in heart failure with preserved ejection fraction (HFpEF), where exercise intolerance is a cardinal symptom, has remained relatively unexplored. The present review summarizes and critically explores the currently limited data on SNS changes in HFpEF patients with a particular emphasis on caveats of the data and the implications for its subsequent interpretation. While direct measurements of SNS activity in HFpEF patients is scarce, modest increases in resting levels of muscle sympathetic nerve activity are apparent, although this may be due to the co-morbidities associated with the syndrome rather than HFpEF per se. In addition, despite some evidence for dysfunctional sympathetic signaling in the heart, there is no clear evidence for elevated cardiac sympathetic nerve activity. The lack of a compelling prognostic benefit with use of β-blockers in HFpEF patients also suggests a lack of sympathetic hyperactivity to the heart. Similarly, while renal and splanchnic denervation studies have been performed in HFpEF patients, there is no concrete evidence that the sympathetic nerves innervating these organs exhibit heightened activity. Taken together, the totality of data suggests limited evidence for elevated sympathetic nerve activity in HFpEF and that any SNS perturbations that do occur are not universal to all HFpEF patients. Finally, how the SNS responds during exertion in HFpEF patients remains unknown and requires urgent investigation.

Visit-to-visit changes in heart rate in heart failure: A pooled participant-level analysis of the PARADIGM-HF and PARAGON-HF trials.

Resting heart rate (HR) is a strong risk marker in patients with heart failure (HF), but the clinical implications of visit-to-visit changes in HR (ΔHR) are less well established. We aimed to explore the association between ΔHR and subsequent outcomes in a pooled dataset of two well-characterized cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF). PARADIGM-HF and PARAGON-HF were randomized trials testing sacubitril/valsartan versus enalapril or valsartan, respectively, in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF). We analysed the association between ΔHR from the preceding visit with the primary endpoint of HF hospitalization (HFH) or cardiovascular death using covariate-adjusted Cox proportional hazards models. A total of 13 194 patients (mean age 67 ± 11 years, 67% men, mean LVEF 40 ± 15%) were included. Over a median follow-up of 2.5 years, 3114 patients experienced a first HFH or cardiovascular death event (10.4 events per 100 patient-years). An increase in HR from the preceding visit, compared with no change, was associated with a higher risk (hazard ratio 1.12; 95% confidence interval [CI] 1.10-1.15; p < 0.001 per 5 bpm increase). Conversely, a drop in HR was associated with a lower risk (hazard ratio 0.97; 95% CI 0.94-1.00; p = 0.044 per 5 bpm drop). The prognostic implications of ΔHR were consistent across the range of LVEF and observed regardless of β-blocker use or presence of a permanent pacemaker. Visit-to-visit increases in HR were especially prognostic in patients without atrial fibrillation (pinteraction = 0.006). Across a broad spectrum of patients with chronic HF, increases in HR from a preceding visit independently predicted clinical outcomes. The detection of notable increases in HR between outpatient visits may help identify patients at heightened risk of adverse events. Clinical Trial Registration; ClinicalTrials.gov NCT01035255 (PARADIGM-HF), NCT01920711 (PARAGON-HF).

Trends in Initial Antihypertensive Medication Prescribing Among >2.8 Million Veterans Newly Diagnosed With Hypertension, 2000 to 2019.

Among patients diagnosed with high blood pressure (BP), initial dual therapy has been recommended for patients with high pretreatment systolic BP (≥160 mm Hg) since 2003, and first-line β-blocker use without a compelling condition has fallen out of favor in US guidelines. This serial cross-sectional study of national Veterans Health Administration data included adult Veterans with incident hypertension initiating antihypertensive medication between January 1, 2000, and December 31, 2019. We assessed annual trends in initial regimens dispensed (index date: first antihypertensive dispense date) by number of classes and unique class combinations used overall and by pretreatment systolic BP (<140, 140 to <160, and ≥160 mm Hg), as well as trends in subgroups (age, sex, race and ethnicity, and comorbidities warranting β-blocker use). Among 2 832 684 eligible Veterans (average age 61 years, 95% men, 65% non-Hispanic White, and 8% with cardiovascular disease), from 2000-2004 to 2015-2019, initial monotherapy increased across all pretreatment systolic BP levels (<140 mm Hg: 62.1% to 66.4%; 140 to <160 mm Hg: 70.7% to 76.8%; ≥160 mm Hg: 64.2% to 69.7%). Initiation of dual therapy decreased across all pretreatment systolic BP levels (<140 mm Hg: 25.0% to 24.2%; 140 to <160 mm Hg: 20.4% to 17.6%; ≥160 mm Hg: 22.7% to 22.0%). Among 2 521 696 Veterans (89% of overall) without a β-blocker-indicated condition in 2015 to 2019, 20% initiated a β-blocker, most commonly as monotherapy. More than half of US Veterans diagnosed with hypertension with a pretreatment systolic BP ≥160 mm Hg were started on antihypertensive monotherapy. There are disparities between guideline-recommended first-line treatments and the actual regimens initiated for newly diagnosed Veterans with hypertension.

Cardiomyopathy-Associated Chronic HeartFailure in Infants Aged

There have been few large-scale studies on the outcomes of cardiomyopathy-associated heart failure (HF) in infants aged <1 year. This study aimed to assess longitudinal echocardiographic outcomes of infants with HF secondary to cardiomyopathy who survived for >1 year. A prospective observational study following 327 infant patients up to 5 years in 2 large pediatric heart centers in Northern China between January 2010 and December 2018. A total of 236 (72.2%) patients had reduced left ventricular ejection fraction (LVEF) (HF with reduced ejection fraction group; LVEF <40%), 91 (27.8%) patients had midrange LVEF (HF with midrange ejection fraction group; LVEF ≥40% but <55%). LVEF improved significantly within the first year and remained stable in years 2 through 5 for both groups. The HF with midrange ejection fraction group had a higher rate of LVEF normalization (hazard ratio, 1.65; P<0.001). Baseline LVEF ≥40%, baseline left ventricular end-diastolic diameter Z score <7.8, the absence of left bundle-branch block, and the absence of β-blocker use were 4 independent favorable predictors for future LVEF normalization. A total of 62.4% of enrolled patients were diagnosed with left ventricular noncompaction. No significant difference in LVEF normalization was found among the different types of cardiomyopathy studied. A significant number of infants with cardiomyopathy who survived >1 year were found to improve with medical therapies during the first year of diagnosis. Poorer outcomes were associated with decreased LVEF and increased heart size at diagnosis baseline, the presence of left bundle-branch block and use of β blockers. The Northern Chinese pediatric population may have a high proportion of left ventricular noncompaction.

Association of β1- and β2-Adrenergic Receptor Gene Polymorphisms with the Effectiveness of Bisoprolol and Carvedilol in Patients with Heart Failure of Ischemic Etiology

The aim. To study the relationship between β1-, β2-adrenergic receptor (β-AR) gene polymorphisms and the effectiveness of bisoprolol and carvedilol in patients with heart failure (HF) and coronary heart disease. Materials and methods. We examined 201 patients with HF on the background of post-infarction cardiosclerosis. Control group included 43 healthy individuals of comparable age and sex. Genotyping was carried out for 3 polymorphisms (rs1801253 and rs1801252 of the β1-AR gene; rs1042714 of the β2-AR gene). The patients were divided into 2 groups: the first group included 104 (51.7%) patients who took bisoprolol during the year of observation; 97 (48.3%) patients of the second group were treated with carvedilol. Statistical analysis was performed using Statistica 10.0 and SNPStats programs. Results. In patients with HF, the mutant C-allele (rs1801253 polymorphism) of the β1-AR gene was associated with a decrease in the probability of heart rate reduction &gt;15 min-1 against the background of the use of β-blocker during the year (odds ratio [OR] = 0.42 [0.16-0.98], p = 0.041, recessive inheritance model; OR = 0.62 [0.40-0.97], p = 0.038; log-additive inheritance model). The probability of positive dynamics of the left ventricular ejection fraction (LVEF) increased in carriers of the wild A-allele of the rs1801252 (Ser49Gly) polymorphism of the β1-AR gene (OR = 4.86 [2.35-10.08], p &lt; 0.0001, codominant model; OR = 5.18 [2.51-10.68], p &lt; 0.0001, dominant model; OR = 4.68 [2.26-9.68], p &lt; 0.0001, over-dominant model; OR = 5.05 [2.48-10.28], p &lt; 0.0001, log-additive inheritance model). The probability of an increase in LVEF within a year increased with treatment with carvedilol in homozygous mutant G/G rs1042714 polymorphism (Gln27Glu) of the β2-AR gene in patients with HF (OR = 6.09 [1.16-31.88], p = 0.038, dominant inheritance model). Conclusions. Patients with HF of ischemic etiology, carriers of the mutant C-allele of rs1801253 polymorphism of the β1-adrenoceptor gene, are worse responders to the use of β-blockers compared to patients with the wild G-allele (a lower proportion of patients with a decrease in heart rate &gt;15 min-1: 6.8% vs. 14.5%, respectively; OR = 0.42 [0.16-0.98], p = 0.041). The frequency of an increase in the value of the LVEF &gt;10% was higher compared to patients with the mutant G-allele (39.3% vs. 11.1%, respectively; OR = 4.86 [2.35-10.08], p &lt; 0.0001) against the background of application of β-blockers. The use of carvedilol was more appropriate in homozygous carriers of the mutant G-allele of the rs1042714 polymorphism (Gln27Glu) of the β2-AR gene compared to bisoprolol (a greater proportion of patients with an increase in the LVEF: 17.6% vs. 9.1%, respectively; OR = 6.09 [1.16-31.88], p = 0.038). No probable associations of rs1801253 and rs1801252 polymorphisms of the β1-AR gene with the pharmacodynamics of bisoprolol and carvedilol in patients with HF of ischemic etiology were found.

Association of beta blockers and mortality in adults with septic shock: systematic review and meta-analysis of randomized clinical trial.

Septic shock still entails significant morbidity and mortality, with the heart being affected due to catecholamine overexpression and direct injury from sepsis. Therefore, the effect of β-blocking the receptors to improve performance is promising when attempting to reverse tachycardia and reduce mortality. We conducted a comprehensive search across five databases for studies published up to 28 January 2024, using a PICO strategy. Ten studies were identified for quantitative analysis and included in our meta-analysis. Our meta-analysis evaluated 28-day in-hospital mortality risk across nine randomized controlled trials (RCTs) involving a total of 1,121 adults with septic shock. We found an association between β-blocker use and reduced overall mortality (OR 0.57; 95% CI 0.34-0.98; I 2: 56%). This effect was significant in the esmolol subgroup (OR 0.47; 95% CI 0.26-0.82; I 2: 32%), but not in the landiolol subgroup (OR 0.98; 95% CI 0.0-1,284.5; I 2: 72%). Additionally, the intervention group shows a significant reduction in HR and lactate levels, as well as an increase in stroke volume index (SVI). In adults with septic shock, β-blockers are associated with a reduction in 28-day in-hospital mortality, a benefit primarily observed with esmolol rather than landiolol. Furthermore, improvements in heart rate (HR) control, lactate levels, and SVI were noted. However, these findings should be interpreted with caution, and further high-quality RCTs comparing different β-blockers are necessary to better elucidate these effects. https://www.crd.york.ac.uk/prospero/, identifier CRD42024513610.

A national analysis of systemic adverse events of beta-blockers used for glaucoma therapy

Purpose To evaluate systemic complications for timolol, carteolol, levobunolol, and/or betaxalol by using an FDA Federal Adverse Event Reporting System (FAERS) Methods We evaluated FAERS for adverse events associated with β-blocker use for glaucoma. All reported symptoms were reviewed to identify systemic adverse events and to detect safety signals, defined as information on a new or known side effect that may be caused by a medicine. We used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC) as a part of a disproportionality analysis comparing the frequency of β-blocker symptoms with all other adverse event reports. We considered a signal to be detected when all four disproportionality analysis metrics were positive. Results We found 10,500,309 total adverse event reports from the FAERS database 2004-2022Q3, which included 8,793 case reports with a primary suspect of a β-blocker use for glaucoma. 1,838 unique adverse symptoms were reported were associated with β-blocker. Regarding outcomes, there were 165 (1.88%) reports of disability, 671 (7.63%) reports of hospitalisation, and 1,934 (21.99%) reports of some other unspecified complication. Regarding adverse events, the most reported general, cardiac, and respiratory symptoms were respectively dizziness (n = 281), bradycardia (n = 145), and dyspnoea (n = 195). 256 (2.91%) cases of death were reported. We found significant signals on bradycardia (n = 145), complete atrioventricular block (n = 38), and bronchospasm (n = 23). No allergic, endocrine, constitutional, or gastrointestinal symptoms generated positive signals. Conclusion β-blocker use in glaucoma therapy can be rarely associated with serious systemic and life-threatening complications.

Effectiveness of β-blockers in improving 28-day mortality in septic shock: insights from subgroup analysis and retrospective observational study.

In recent years, septic shock remains a common fatal disease in the intensive care unit (ICU). After sufficient fluid resuscitation, some patients still experience tachycardia, which may lead to adverse effects on cardiac function. However, the use of β-blockers in the treatment of septic shock remains controversial. Thus, the purpose of this study is to evaluate the efficacy of β-blockers in the treatment of patients with septic shock and explore the most appropriate patient subgroups for this treatment. This retrospective observational study enrolled septic shock patients from the Medical Information Mart for Intensive Care (MIMIC)-IV and used propensity score matching (PSM) to balance some baseline differences between patients with and without β-blockers treatment. The primary outcome was the 28-day mortality. Length of stay (LOS) in the ICU and hospital, and the degree of support for organs such as circulatory, respiratory and renal systems were also assessed. Subgroup analysis and multivariate logistic regression were performed to determine the relationship between β-blockers therapy and 28-day mortality in different patient groups. A total of 4,860 septic shock patients were enrolled in this study and 619 pairs were finally matched after PSM. Our analysis revealed that β-blocker therapy was associated with a significant improvement in 28-day mortality (21.5% vs. 27.1%; P = 0.020) and led to a prolonged LOS in both the ICU and hospital. Subgroup analysis indicated that there was an interaction between cardiovascular diseases and β-blocker therapy in patients with septic shock. Patients with pre-existing heart disease or atrial arrhythmias were more likely to derive benefits from β-blocker treatment. We found β-blockers therapy was effective to improve 28-day mortality in patients with septic shock. Patients in the subgroup with cardiovascular diseases were more likely to benefit from β-blockers in mortality.

In MI with preserved LVEF, long-term β-blocker use vs. no use did not reduce all-cause death or MI at 3.5 y.

Yndigegn T, Lindahl B, Mars K, et al; REDUCE-AMI Investigators. Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med. 2024;390:1372-1381. 38587241.

An Update on Guidelines to Prevent and Manage Atrial Fibrillation After Cardiac Surgery and a Survey of Practice in the UK

ObjectivesPostoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and affects around 30% of patients. Variable guidelines from multiple organisations exist for the prevention of POAF after cardiac surgery. We conducted a survey of UK practice was conducted to define “usual care” for a platform trial of interventions to prevent POAF after cardiac surgery. To provide context for the survey, we reviewed all current guidelines for the prevention and management of AF after cardiac surgery. DesignOnline survey and literature review SettingSurvey: All 35 UK National Health Service Cardiac Surgery Centres. Literature Review: Guidelines from specialist societies and other guideline making organisations from the UK, Europe and North America. ParticipantsEstablished link network of researchers. Measurements and Main ResultsReview: Five relevant guidelines were identified. All guidelines recommend β-blockade for prevention of AF after cardiac surgery. Treatment of AF is recommended using either rate or rhythm control. Cardioversion is recommended only for the haemodynamically unstable patient. Patients who remain in AF for over 48 hours should be considered for anticoagulation. Patients should be followed up within 60 days to review the need for anti-arrhythmic and anticoagulant therapy. Survey: 31/35 (89%) of centres responded. 11 of 31 (35.5%) centres followed local guidance for prevention of POAF, 4 (13%) centres followed Society of Cardiovascular Anesthesiologists / European Association of Cardiothoracic Anaesthesia guidelines, 4 (13%) followed UK National Institute of Health and Care Excellence guidance and 4 followed “other” guidance. 8 of 31 (26%) followed no guidelines to prevent POAF. 28 of 31 (90%) centres did not risk-stratify their patients for POAF. Most centres (23/31, 74%) do not have a care-package in place to prevent POAF, but 14 of 31 (45%) try in some way to prevent AF in patients presenting in sinus rhythm. The most common interventions to prevent POAF are β-blocker use post-operatively (23/31, 74%), use of magnesium (20/31, 64.5%) and maintaining a serum K+ ≥4.5mmol/L (26/31, 84%). ConclusionsGuidance to prevent AF after cardiac surgery clusters around the use of β-blockade. Although patients in the UK do not appear to be risk-assessed for POAF, the main interventions used to prevent it are similar; β-blockade and maintenance of serum K+ and Mg2+ levels.

Comparison of allergy prevalence using brinzolamide 1.0% / brimonidine 0.2% fixed combination with and without β-blocker in glaucoma patients: a retrospective cohort study

BackgroundGlaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent β-blocker.MethodsOf these, 176 patients used a β-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent β-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan–Meier survival analysis.ResultsAllergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent β-blocker-usage groups, respectively. Kaplan–Meier survival analysis indicated that half of the allergies in the concurrent β-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent β-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent β-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent β-blocker-usage group.ConclusionsConcurrent use of β-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of β-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.

Efficacy and safety of hymenoptera venom immunotherapy.

Background: Being stung by Hymenoptera species can cause life-threatening anaphylaxis. Although venom immunotherapy (VIT) seems to be the most effective treatment, its long-term efficacy, and risk factors for adverse events remain unclear. Objective: The objective was to investigate the long-term efficacy of VIT and evaluate adverse events and risk factors related to this. Method: Patients who received VIT in a tertiary-care adult allergy clinic between January 2005 and July 2022 were included. Patients' data were compared with those of individuals who had been diagnosed with bee and/or wasp venom allergy during the same period but had not received VIT and experienced field re-stings. Results: The study included 105 patients with venom allergy, of whom 68 received VIT and 37 did not receive VIT. Twenty-three patients (34%) completed 5 years of VIT, and the overall mean ± standard deviation VIT duration was 46.9 ± 20.9 months. Re-stings occurred in 5 of 23 patients who completed 5 years of VIT, and none of them developed a systemic reaction. Eighteen patients (40%) experienced re-stings after prematurely discontinuing VIT, of whom eight (44%) developed a systemic reaction. In the control group of patients who did not receive VIT, 26 patients (70.3%) experienced re-stings, and all had systemic reactions (100%), with no change in their median Mueller scores. There was a significant difference in the median Mueller score change between the patients who received VIT and the controls who did not (p = 0.016). A total of 13 patients (19%) experienced adverse events while receiving VIT, which were systemic reactions in nine honeybee VIT. The use of β-blockers was determined as the most important risk factor (odds ratio 15.9 [95% confidence interval, 1.2-208.8]; p = 0.035). Conclusion: It was confirmed that VIT was effective in both reducing the incidence and the severity of re-sting reactions. These effects were more pronounced in the patients who completed 5 years of VIT.

β-blockades and the risk of atrial fibrillation in patients with cardiovascular diseases.

β-blockers have been widely used in patients with extensive cardiovascular disease (CVD) and have provided benefits. However, they are more likely to cause symptomatic bradycardia, hypotension, or glucose metabolism disorders, which may lead to an increased risk of atrial fibrillation (AF), but evidence is lacking. This study was to analyze the association between the use of β-blockers and the risk of developing AF. This nationwide, prospective cohort study utilized data from the 2013-2020 National Health and Nutrition Examination Survey (NHANES). The patients were stratified into a β-blocker treatment group (n = 2585) and a non-β-blocker treatment group (n = 8525). Univariate and multivariate logistic regression analyses were performed to identify the relationship between β-blockades and the risk of AF. Propensity matching analysis was used to balance patient baseline characteristics and to control for confounders. A total of 11,110 subjects were included in this study (mean [SD] age, 59.89 [15.07] years; 5657 [49.7%] males). A total of 111/2585 subjects developed AF in the β-blocker treatment group, and 75/8525 developed AF in the non-β-blocker treatment group (incidence rate, 4.2% vs. 0.8%). Compared with the non-β-blocker group, the β-blocker group had an increased risk of incident AF (aOR, 2.339; 95% CI, 1.614-3.410). Some sensitivity analyses also revealed consistent findings of increased AF risk associated with β-blocker treatment. The findings from this study suggest that β-blocker treatment is associated with an increased risk of incident AF and may help physicians select a modest medication for patients while also assessing the risk of AF.