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Background: Beta‐blocker therapy, a treatment burdened by side effects including fatigue, erectile dysfunction and depression, was shown to reduce mortality and cardiovascular events after acute coronary syndromes (ACS) in the pre‐coronary reperfusion era. Potential mechanisms include protection from ventricular arrhythmias, increased ischaemia threshold and prevention of left ventricular (LV) adverse remodelling. With the advent of early mechanical reperfusion and contemporary pharmacologic secondary prevention, the benefit of beta‐blockers after ACS in the absence of LV dysfunction has been challenged. Methods: The present narrative review discusses the contemporary evidence based on searching the PubMed database and references in identified articles. Results: Recently, the REDUCE‐AMI trial—the first adequately powered randomized trial in the reperfusion era to test beta‐blocker therapy after myocardial infarction with preserved left ventricular ejection fraction (LVEF)—showed no benefit on the composite of all‐cause death or myocardial infarction over a median 3.5‐year follow‐up. While the benefit of beta‐blockers in patients with reduced LVEF remains undisputed, their value in post‐ACS patients with mildly reduced systolic function (LVEF 41%–49%) has not been studied in contemporary randomized trials; in this setting, observational studies have suggested a reduction in cardiovascular events with these agents. The adequate duration of beta‐blocker therapy remains unknown, but observational data suggests that any mortality benefit may be lost beyond 1–12 months after ACS in patients with LVEF >40%. Conclusion: We believe that there is sufficient evidence to abandon routine beta‐blocker prescription in post‐ACS patients with preserved LV systolic function. [ABSTRACT FROM AUTHOR]

Aims: The efficacy of beta‐blockers in cardiac amyloidosis (CA) is unclear, and concerns persist that neurohormonal blockade could worsen symptoms of heart failure. We aimed to assess whether beta‐blocker therapy is associated with improved survival in patients with CA. Methods and results: We conducted a systematic review and meta‐analysis to examine the impact of beta‐blocker therapy on mortality in patients with CA. A search of MEDLINE and EMBASE was performed in August 2023. Data were extracted from observational studies and synthesized with pooling and random effects meta‐analysis. Thirteen studies including 4215 patients with CA were incorporated in this review (3688 transthyretin amyloid cardiomyopathy (ATTR‐CM), 502 light chain amyloid cardiomyopathy (AL‐CM), 25 not specified; age 74.8 ± 5.5 years, 76% male). Over half of the cohort (52%) received beta‐blockers and the rate of beta‐blocker withdrawal was 28%. All‐cause mortality was 33% (range: 13–51%) after a median follow‐up ranging from 13 to 36 months. There was an inverse association between the pooled risk of mortality and the use of beta‐blocker therapy at any time point (RR 0.48, 95% CI 0.29–0.80, I2 = 83%, P = 0.005, seven studies). There was no association between mortality and beta‐blocker use (RR 0.65, 95% CI 0.29–1.47, I2 = 88%, P = 0.30) in the three studies that only included patients with ATTR‐CM. The three studies that included patients with both ATTR‐CM and AL demonstrated an association of beta‐blocker use with reduced mortality (OR 0.43, 95% CI 0.29–0.63, I2 = 4%, P < 0.001). The only study that solely included 53 patients with AL‐CM, demonstrated improved survival among the 53% who were able to tolerate beta‐blocker therapy (RR 0.26, 95% CI 0.08–0.79, P = 0.02). The absence of information on staging of CA is an important limitation of this study. Conclusions: Treatment with beta‐blockers may be associated with a survival benefit in patients with CA, but these findings are subject to selection and survivor biases. Definitive prospective randomized trials of conventional heart failure therapies are needed in CA. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Beta‐blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho‐inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta‐blocker compared to those treated with a beta‐blocker.We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta‐blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM‐HF. The primary outcome was time to first heart failure hospitalization or cardiovascular death. Compared to the 7811 patients taking a beta‐blocker, the 588 patients not receiving a beta‐blocker were older, more frequently female, but had a similar mean left ventricular ejection fraction and New York Heart Association class distribution, with little difference in N‐terminal pro‐B‐type natriuretic peptide. Patients not taking beta‐blockers had a higher rate of the primary endpoint than those taking beta‐blockers. The benefit of sacubitril/valsartan on the primary endpoint was evident in both the no beta‐blocker subgroup (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.45–0.82) and the beta‐blocker subgroup (HR 0.82, 95% CI 0.75–0.90; p‐interaction = 0.06). The respective HRs for cardiovascular death were 0.47 (95% CI 0.32–0.69) versus 0.84 (95% CI 0.75–0.95; p‐interaction <0.01) and for HF hospitalization 0.76 (95% CI 0.51–1.12) versus 0.80 (95% CI 0.71–0.90; p‐interaction = 0.73). For all‐cause death, the HR in the no beta‐blocker group was 0.50 (95% CI 0.36–0.71) compared to 0.89 (95% CI 0.80–0.99) in the beta‐blocker group (p‐interaction <0.01). Safety outcomes related to sacubitril/valsartan versus enalapril did not differ according to background beta‐blocker use.Sacubitril/valsartan may be more effective than enalapril in reducing the risk of death in patients not treated with a beta‐blocker compared to those treated with a beta‐blocker, but is effective regardless of beta‐blocker use.Clinical Trial Registration: ClinicalTrials.gov NCT01035255. [ABSTRACT FROM AUTHOR]

Introduction: Early‐onset atrial fibrillation (AF) has already been observed in approximately 2% of patients with genetically proven long QT syndrome (LQTS). This frequency is higher than population‐based estimates of early‐onset AF. However, the concomitant expression of AF in LQTS is likely underestimated. The purpose of this study was to examine the clinical presentation, genetic background, and outcomes of a cohort of patients with LQTS and early‐onset AF referred to a single tertiary center. Methods: Twenty‐seven patients diagnosed with congenital LQTS were included in the study based on the documentation of early‐onset (age ≤50 years) clinical or subclinical AF episodes in all available medical records, including standard electrocardiograms, wearable monitor or cardiac implantable electronic devices. Results: Seventeen patients experienced clinical AF during the follow‐up period. Subclinical AF was detected in 10 patients through insertable or wearable cardiac monitors. In our series, the mean heart rate during AF episodes was found to be relatively low despite the patients' young age and the low or minimal effective doses of beta‐blockers used for QTc interval control. All patients exhibiting LQTS and early‐onset AF were genotype positive, carrying mutations in the KCNQ1 (66%), KCNH2, KCNE1, and SCN5A genes. Notably, most of these patients carried the same p.(R231C) mutation in the KCNQ1 gene (59%) and were from the same families, suggesting concurrent expression of familial AF and LQTS. Conclusion: LQTS patients are prone to developing clinical and subclinical AF, even at a younger age. The occurrence of early‐onset AF in the LQTS population could be more frequent than previously assumed. AF should be considered as a potential dysrhythmia related to LQTS. Our study emphasizes the importance of carefully researching clinical and/or subclinical episodes of AF through strict heart rhythm monitoring in the LQTS population. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Methods and results Conclusions In the absence of randomized trial evidence, we performed a large observational analysis of the association between beta‐blocker (BB) use and clinical outcomes in patients with heart failure (HF) and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF).We pooled individual patient data from four large HFmrEF/HFpEF trials (I‐Preserve, TOPCAT, PARAGON‐HF, and DELIVER). The primary outcome was the composite of cardiovascular death or HF hospitalization. Among the 16 951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12 812 patients (75.6%) received a BB. The median bisoprolol‐equivalent dose of BB was 5.0 (Q1–Q3: 2.5–5.0) mg with BB continuation rates of 93.1% at 2 years (in survivors). The unadjusted hazard ratio (HR) for the primary outcome did not differ between BB users and non‐users (HR 0.98, 95% confidence interval [CI] 0.91–1.05), but the adjusted HR was lower in BB users than non‐users (0.81, 95% CI 0.74–0.88), and this association was maintained across LVEF (pinteraction = 0.88). In subgroup analyses, the adjusted risk of the primary outcome was similar in BB users and non‐users with or without a history of myocardial infarction, hypertension, or a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (pintreraction = 0.02).In this observational analysis of non‐randomized BB treatment, there was no suggestion that BB use was associated with worse HF outcomes in HFmrEF/HFpEF, even after extensive adjustment for other prognostic variables. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta‐blocker therapy (BB) and compare it to healthy controls. Methods: Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age‐groups and four heart rate (HR) ranges. Results: In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age‐groups compared to controls at HR 120–140 bpm (1–15 years: p <.01; 15–18 years: p =.03). At HR 80–100, LQT1 patients aged 1–10 years had lower HF than LQT2 patients (1–5 years: p =.05; 5–10 years: p =.02), and LQT2 patients aged 15–18 years had lower HF than LQT1 patients (p <.01). Symptomatic patients aged 10–15 years had lower PTOT at HR 100–120 bpm than asymptomatic patients (p =.04). LQT1 girls aged 10–15 and 15–18 years had a lower PTOT (10–15 years: p =.04; 15–18 years: p =.02) than boys. Conclusion: This study shows a correlation between HR and changes in HRV parameters. At higher HRs, LQTS patients generally had lower HRV values than controls, suggesting an abnormal autonomic response. These results may strengthen the link between physical activity and arrhythmias in LQTS. [ABSTRACT FROM AUTHOR]

Aims: Guidelines recommend target doses (TD) of heart failure (HF) with reduced ejection fraction (HFrEF) medications regardless of sex. Differences in pharmacokinetics and pharmacodynamics may explain heterogeneity in treatment response, adverse reactions, and tolerability issues across sexes. The aim of this study was to explore sex‐based differences in the association between TD achievement and mortality/morbidity in HFrEF. Methods and results: Patients with HFrEF and HF duration ≥6 months registered in the Swedish HF Registry between May 2000 and December 2020 (follow‐up until December 2021) were analysed. Treatments of interest were renin–angiotensin system inhibitors (RASI) or angiotensin receptor–neprilysin inhibitors (ARNI), and beta‐blockers. Multivariable Cox regression models were performed to explore the risk of cardiovascular mortality or hospitalization for HF across dose categories in females versus males. A total of 17 912 patients were analysed (median age 77.0 years, interquartile range [IQR] 70.0–83.0), 29% were female. Over a median follow‐up of 1.33 years (IQR 0.29–3.22), for RASI/ARNI there was no significant difference in outcome for females achieving 50–99% versus 100% of TD (hazard ratio 0.92, 95% confidence interval 0.83–1.03), whereas males showed a gradual lowering in risk together with the achievement of higher % of TD (p‐interaction = 0.030). For beta‐blockers the achievement of TD was associated with the lowest risk of outcome regardless of sex. Conclusions: Our findings suggest that females and males might differently benefit from the same dose of RASI/ARNI, and do represent a general call for randomized controlled trials to consider sex‐specific up‐titration schemes when testing HFrEF treatments in need of up‐titration. [ABSTRACT FROM AUTHOR]

Background: 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. Hypothesis: 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). Methods: 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. Results: 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). Conclusion: 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. Key points: Rate control is the most commonly employed first‐line management strategy for atrial fibrillation in patients with chronic kidney disease. Evidence to guide selection between beta‐blockers and nondihydropyridine calcium channel blockers is scarce.This is the first study to compare patients with atrial fibrillation under rate‐control strategy according to renal function.In patients with glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2, both nondihydropyridine calcium channel blockers (ND‐CCB) and beta‐blockers therapy have good results in heart rate (HR) control, while in advanced chronic kidney disease (GFR < 30 mL/min/1.73 m2), a possible association of ND‐CCB with increased hospitalizations due to poor HR control was detected. [ABSTRACT FROM AUTHOR]

Introduction: During ventricular pacing, a fusion of atrial activation may occur owing to the simultaneous retrograde conduction of the atrioventricular (AV) node and accessory pathway (AP), potentially leading to an inaccurate mapping of the atrial AP insertion site. Objective: We tested the hypothesis that landiolol, an ultra‐short‐acting intravenous β1‐blocker, could dissociate a fusion of atrial activation. Methods: We conducted a prospective before‐and‐after study to investigate the effect of landiolol on retrograde conduction via the AV node and AP. We enrolled 21 consecutive patients with orthodromic AV reciprocating tachycardia who underwent electrophysiological studies at our hospital between January 1, 2018, and August 31, 2020. Results: Six patients exhibited a fusion of atrial activation. After landiolol administration (10 μg/kg/min), the effective refractory period was unchanged in AP (280 [240–290] ms vs. 280 [245–295] ms, p =.91), whereas that of the AV node was prolonged (275 [215–380] ms vs. 332 [278–445] ms, p =.03). The Wenckebach pacing rate via retrograde AV node decreased after landiolol administration (180 [140–200] beats per minute [bpm] vs. 140 [120–180] bpm, p =.02). Thus, landiolol decreased the minimum ventricular pacing rate required to dissociate a fusion of atrial activation (180 [160–200] bpm vs. 140 [128–155] bpm, p =.007). Radiofrequency catheter ablation under landiolol administration successfully eliminated AP in all patients during ventricular pacing without complications or recurrence. Conclusion: Landiolol inhibited the AV node without affecting the AP and helped dissociate a fusion of atrial activation at a lower ventricular pacing rate. [ABSTRACT FROM AUTHOR]

In the article, the authors present their study on the trend of beta-blocker doses in various age groups among older people with heart failure with reduced ejection fraction (HFrEF). Also cited are the use of the Medicare Fee-for-Service (FFS0 claims data in the study, and the recommended target doses from the 2013 American College of Foundation/American Heart Association for HF management.

Anxiety is a critical component of the development and maintenance of drug addiction; however, anti‐anxiety medications such as benzodiazepines and beta‐blockers (β‐adrenergic receptor antagonists) are not used for the treatment of substance use disorder, except for the management of acute withdrawal syndrome. Preclinical studies have shown that beta‐blockers may reduce stress‐induced relapse; however, the effect of beta blockers on the escalation and maintenance of drug intake has not been tested. To address this issue, we chronically administered the β‐adrenergic receptor antagonist propranolol during the escalation or maintenance of cocaine intake in a model of extended access (6 h) to cocaine self‐administration (0.5 mg/kg). The behavioural specificity of propranolol was tested using a non‐drug reward (saccharin). Daily administration of propranolol (15 mg/kg) prevented the development of escalation of cocaine self‐administration and partially reversed self‐administration after the establishment of escalation of intake. Moreover, propranolol dose‐dependently decreased the motivation for cocaine tested under a progressive ratio schedule of reinforcement during the development of escalation and after maintenance. Finally, propranolol administration had no effect on the escalation and maintenance of saccharin self‐administration. These results demonstrate that chronic treatment with propranolol provides therapeutic efficacy in reducing cocaine self‐administration during the development and after the establishment of escalation of cocaine self‐administration in an animal model relevant to cocaine use disorder. These results suggest that beta blockers should be further investigated as a target for medication development for the treatment of cocaine use disorder. [ABSTRACT FROM AUTHOR]

Summary: We recruited 5,970 hypertensive patients with obstructive sleep apnea (OSA) on current antihypertensive treatment from the European Sleep Apnea Database (ESADA) cohort. The group was subdivided into those receiving monotherapy (n = 3,594) and those receiving dual combined therapy (n = 2,376). We studied how major OSA confounders like age, gender, and body mass index as well as the degree of sleep apnea modified office systolic and diastolic blood pressure. Beta‐blockers alone or in combination with a diuretic were compared with other antihypertensive drug classes. Monotherapy with beta‐blocker was associated with lower systolic blood pressure, particularly in non‐obese middle‐aged males with hypertension. Conversely, the combination of a beta‐blocker and a diuretic was associated with lower systolic and diastolic blood pressure in hypertensive patients with moderate–severe OSA. Systolic blood pressure was better controlled in female patients using this combined treatment. Our cross‐sectional data suggest that specific clinical characteristics and type of antihypertensive medication influence the degree of blood pressure control in hypertensive OSA patients. Controlled trials are warranted. [ABSTRACT FROM AUTHOR]

Aims: Beta‐blockers are proven to improve survival among patients with heart failure with reduced ejection fraction. Their efficacy in patients with heart failure with reduced ejection fraction and pacemaker devices has not been demonstrated. Our aim was to test the hypothesis that beta‐blocker therapy is associated with improved survival in patients with chronic heart failure and a pacemaker rhythm on electrocardiogram (ECG). Methods and results: This is a post hoc analysis from the GISSI‐HF randomized clinical trial. We evaluated efficacy of beta‐blockers by creating Cox proportional hazards models adjusting for pacemaker rhythm and heart rate, among other variables. Interactions between pacemaker rhythm, heart rate, and beta‐blocker were also examined. Of the 6975 patients enrolled in the GISSI‐HF trial, 813 (11.7%) had a pacemaker rhythm on baseline ECG. Of these 813 patients, 511 (62.9%) were receiving beta‐blocker therapy. The effect of beta‐blocker therapy on mortality was assessed using multivariable Cox proportional hazards adjusted for 27 co‐variates. In the whole cohort, beta‐blocker therapy was significantly associated with reduced mortality (hazard ratio 0.79 [0.72–0.87], P < 0.001), without interaction between beta‐blockers, pacemaker rhythm and heart rate. Beta‐blocker therapy was beneficial in the sub‐group restricted to baseline pacemaker rhythm (hazard ratio 0.62 [0.49–0.79], P < 0.001). Conclusions: Beta‐blocker therapy is associated with improved survival among patients with heart failure and a pacemaker rhythm on ECG. Further studies are necessary to analyse differences between atrial and ventricular pacemakers. [ABSTRACT FROM AUTHOR]

Aims: Cachexia, a common manifestation of malignant cancer, is not only associated with weight loss, but also with severe cardiac atrophy and impaired cardiac function. Here, we investigated the effects of ACM‐001 (0.3 or 3 mg/kg/day) in comparison to carvedilol (3 or 30 mg/kg/day), metropolol (50 or 100 mg/kg/day), nebivolol (1 or 10 mg/kg/day) and tertatolol (0.5 or 5 mg/kg/day) on cardiac mass and function in a rat cancer cachexia model. Methods and results: Young male Wistar Han rats were inoculated i.p. with 108 Yoshida hepatoma AH‐130 cells and treated once daily with verum or placebo by gavage. Cardiac function (echocardiography), body weight and body composition (nuclear magnetic resonance scans) were assessed. The hearts of animals were euthanized on day 11 (placebo and 3 mg/kg/day ACM‐001) were used for signalling studies. Beta‐blockers had no effect on tumour burden. ACM‐001 reduced body weight loss (placebo: −34 ± 2.4 g vs. 3 mg/kg/day ACM‐001: −14.8 ± 8.4 g, p = 0.033). Lean mass wasting was attenuated (placebo: −16.5 ± 2.34 g vs. 3 mg/kg/day ACM‐001: −2.4 ± 6.7 g, p = 0.037), while fat loss was similar (p = 0.4) on day 11. Placebo animals lost left ventricular mass (−101 ± 14 mg), which was prevented only by 3 mg/kg/day ACM‐001 (7 ± 25 mg, p < 0.01 vs. placebo). ACM‐001 improved the ejection fraction (EF) (ΔEF: placebo: −24.3 ± 2.6 vs. 3 mg/kg/day ACM‐001: 0.1 ± 2.9, p < 0.001). Cardiac output was 50% lower in the placebo group (−41 ± 4 ml/min) compared to baseline, while 3 mg/kg/day ACM‐001 preserved cardiac output (−5 ± 8 ml/min, p < 0.01). The molecular mechanisms involved inhibition of protein degradation and activation of protein synthesis pathways. Conclusion: This study shows that 3 mg/kg/day ACM‐001 restores the anabolic/catabolic balance in cardiac muscle leading to improved function. Moreover, not all beta‐blockers have similar effects. [ABSTRACT FROM AUTHOR]

The authors performed a meta‐analysis to assess the efficacy of non‐atenolol β‐blockers as add‐on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β‐blockers with diuretics, calcium channel blockers (CCBs), angiotensin‐converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β‐blockers add‐on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non‐β‐blocker monotherapy (weighted mean difference in mm Hg [95% confidence interval]: −4.1 [−6.0, −2.2] and −3.7 [−4.6, −2.8], respectively). These results were consistent across the comparisons with diuretics (systolic pressure, −10.2 [−14.2, −6.2]; diastolic pressure, −5.4 [−8.2, −2.6]), CCBs (systolic pressure, −4.1 [−7.1, −1.0]; diastolic pressure, −2.8 [−4.1, −1.5]), and ACEIs/ARBs (systolic pressure, −2.9 [−4.3, −1.5]; diastolic pressure, −4.2 [−5.0, −3.4]). There was no significant difference in blood pressure lowering effects between combinations with and without a β‐blocker (systolic pressure, −1.3 mm Hg [−5.8, 3.2]; diastolic pressure, −.3 mm Hg [−2.7, 2.1]). Metoprolol add‐on or combination therapy had a significantly greater blood pressure reduction than non‐β‐blocker therapy (systolic pressure, −3.6 mm Hg [−5.9, −1.3]; diastolic pressure, −2.1 mm Hg [−3.5, −.7]). In conclusion, non‐atenolol β‐blockers are effective in lowering blood pressure as add‐on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β‐blockers can and should be used in combination with other antihypertensive drugs. [ABSTRACT FROM AUTHOR]

Extracorporeal life support (ECLS) improves circulation in life‐threatening cardiac dysfunction or arrest patients. Its benefits in drug‐induced cardiovascular complications are debated. Indications and outcomes are poorly established. We performed a narrative review discussing ECLS indications, timing and results in cardiotoxicant‐poisoned patients. The review was focused on antiarrhythmic drugs and aluminium phosphide. Literature analysis was limited to the past 30 years in adults. Most reports were single cases and retrospective except one prospective case series of limited size, two of them controlled. ECLS indications and timing were at the discretion of physicians in charge but mostly included persistent cardiovascular failure despite elevated doses of inotropic/vasopressor support associated with elevated blood lactate concentrations (usually, >5 mmol/L) and collapsed left ventricular ejection fraction (LVEF; usually, ≤40%). Survival improved using ECLS versus standard care in one study. Survival was ~80% if ECLS was implemented in refractory cardiovascular failure and 25%–66% if implemented in cardiac arrest. In two controlled studies, survival of ECLS‐treated aluminium phosphide‐poisoned patients was improved versus standard care, if implemented in the presence of systolic blood pressure ≤80 mmHg despite inotropic/vasopressor treatment, arterial pH ≤ 7.0 and LVEF ≤ 40%. Despite low‐to‐moderate level of evidence, ECLS seems effective to improve survival in selected cardiotoxicant‐poisoned patients. Selection criteria need clarification. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular medications are vital for the secondary prevention of coronary arterial disease (CAD). However, the effect of cardiovascular medication may depend on the optimal adherence of the patients. This meta‐analysis aims to determine the magnitude of adherence to vascular medications that influences the absolute and relative risks (RRs) of mortality in patients with CAD in real‐world settings. Methods: The Cochrane Library, PubMed, and EMBASE databases were searched through March 1, 2022. Prospective studies reporting association as RR and 95% confidence interval between cardiovascular medication adherence and any cardiovascular events and/or all‐cause mortality in patients with CAD were included. A one‐stage robust error meta‐regression method was used to summarize the dose‐specific relationships. Results: A total of 18 studies were included. There is a significant inverse linear association between cardiovascular medication adherence and cardiovascular events (pnonlinearity =.68) or mortality (pnonlinearity =.82). The exposure‐effect analysis showed that an improvement of 20% cardiovascular medication adherence was associated with 8% or 12% lower risk of any cardiovascular events or mortality, respectively. In subgroup analysis, the benefit was observed in adherence of stain (RR: 0.90, for cardiovascular events, RR: 0.85, for mortality), angiotensin‐converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB)(RR: 0.90, for mortality), and antiplatelet agent (RR: 0.89 for mortality) but not in beta‐blocker (RR: 0.90, p =.14, for cardiovascular events, RR: 0.97, p =.32 for mortality). Estimated absolute differences per 1 million individuals per year for mortality associated with 20% improvement were 175 cases for statin, 129 cases for antiplatelet, and 117 cases for ACEI/ARB. Conclusion: Evidence from the real word showed poor adherence to vascular medications contributes to a considerable proportion of all cardiovascular disease events and mortality in patients with CAD. [ABSTRACT FROM AUTHOR]

Two cases of pyogenic granulomas in burned skin were presented, a 17‐month‐old boy and a 7‐year‐old girl, being given oral propranolol and topical timolol. Both cases showed lesions improvement with no adverse effects, suggesting that beta‐blocker therapy may have a positive impact on the treatment of pyogenic granuloma after burns. [ABSTRACT FROM AUTHOR]

Aims: The optimal treatment for severe aortic valve disease complicated with moderate function mitral regurgitation (FMR) remains controversial. Although isolated surgical aortic valve replacement (SAVR) is reasonable, previous studies also show that moderate FMR might deteriorate after surgical treatment and result in poorer prognosis. Because the left ventricular remodelling plays a critical role in the development of FMR, these patients might potentially benefit from the administration of β‐blocker (BB). Unfortunately, relevant clinical evidence is lacking. This study aimed to investigate the impact of post‐operative administration of BB on the outcomes of moderate FMR patients undergoing isolated SAVR. Methods: In this single‐centre cohort study, patients who underwent isolated SAVR and complicated with pre‐operative moderate FMR during 2010 and 2019 at our centre were retrospectively recruited. Patients were divided into two groups according to postoperative administration of BB (BB group vs. control group). The cumulative survival rates were calculated using the Kaplan–Meier method and tested by the log‐rank test, followed by inverse probability treatment weighting (IPTW) analysis to further control the between‐group imbalances. The primary outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), a composite endpoint of all‐cause death, repeat heart valve surgery, non‐fatal myocardial infarction, stroke, and hospitalization for heart failure. Results: A total of 165 patients were enrolled, 57 (34.6%) of whom were female, and the mean age was 59.2 ± 12.2 years. Eighty (48.5%) patients received post‐operative BB therapy. The median follow‐up time was 18.4 months. The administration of BB was not associated with lower risk of MACCE [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.29–1.62, P = 0.388] or all‐cause death (HR: 1.03, 95% CI: 0.30–0.56, P = 0.967). In the IPTW dataset, the total number of patients were 326.89, and the outcomes regarding the risk of MACCE (HR: 0.79, 95% CI: 0.31–1.97, P = 0.607) and all‐cause death (HR: 1.33, 95% CI:0.35–5.05, P = 0.674) were in line with the unmatched analysis. The follow‐up echocardiographic results were available for 72.2% of the overall cohort, and the use of BB was observed to be associated with higher improvement rate of follow‐up FMR according to the IPTW analysis (92.2% vs. 98.3%, P = 0.033). Conclusions: The administration of BB after SAVR was not associated with lower risk of MACCE for patients of severe aortic valve disease complicated with moderate FMR, but was potentially beneficial for improving FMR. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate French pharmacovigilance data. The objective was to characterize psoriatic conditions that occurred after beta‐blocker (BB) exposure and bring to light a possible pharmacovigilance signal. Methods: Spontaneous reports of psoriatic conditions recorded in the French National Pharmacovigilance Database (FPVD) between 1985 and 2019 were extracted. We performed a retrospective, descriptive analysis of reports linked to BB exposure. Association between psoriasis risk and BB exposure was assessed using a case/noncase study. Results: Two hundred and twenty‐five reports of psoriatic conditions after BB exposure were recorded in the FPVD during the study period. Both cardioselective and noncardioselective, topical and systemic BBs are involved. Therapeutic indication of BB was mainly hypertension. Mean time to onset was 5 months and outcome was favourable in 68% after BB discontinuation. These features were concordant with those of literature reports. The reporting odds ratio (ROR) was 8.95 (95% confidence interval 7.75‐10.33). Conclusion: We highlighted a statistically significant disproportionality which constitutes a pharmacovigilance signal. Psoriasis risk with BBs is a class effect. Increasing surveillance during the first year of BB exposure is needed. [ABSTRACT FROM AUTHOR]

Introduction: Beta‐blockers are prescribed for many pregnant women with heart disease, but whether there is a dose‐dependent effect on fetal growth remains to be examined. We aimed to investigate if antenatal beta‐blocker use and dose were associated with delivering a small‐for‐gestational‐age infant among women with heart disease. Material and methods: Our cohort included women with heart disease who delivered at Oslo University Hospital between 2006 and 2015. Maternal heart disease was classified into modified WHO risk scores. Women with beta‐blocker treatment were dichotomized into whether they had been treated with a low or high dose based on clinical factors. We compared the risk of delivering a small‐for‐gestational‐age infant in women exposed to high doses, low doses, or with no exposure to antenatal beta‐blockers while adjusting for severity of maternal heart disease in logistic regression models. Results: Of a total of 540 pregnancies among women with heart disease, 163 (30.2%) were exposed to beta‐blocker treatment. The majority were treated with metoprolol (86.5%). Almost twice as many babies in the beta‐blocker group were small‐for‐gestational‐age, compared with the non‐exposed group (19.8 vs 9.5%, P < 0.001). Women using a high‐dose beta‐blocker had a five‐fold increased risk of delivering a small‐for‐gestational‐age infant compared with non‐exposure (adjusted odds ratio [aOR] 4.89, 95% confidence interval [CI] 2.22–10.78, P < 0.001). Women using a low dose of beta‐blocker had a two‐fold increased risk of delivering a small‐for‐gestational‐age infant; however, the confidence interval included the null (aOR 1.75, 95% CI 0.83–3.72, P = 0.143). Results when restricting the analyses to metoprolol showed the same pattern, but with attenuation of risks. Conclusions: We found a five‐fold increased risk of delivering a small‐for‐gestational‐age infant in women with heart disease treated with a high dose of beta‐blocker, and a two‐fold increased risk among those treated with a low dose, showing an apparent dose–response relation. Close monitoring of fetal growth is warranted among women with heart disease treated with beta‐blockers. As drug therapy in pregnancy concerns both mother and fetus, an optimum balance for both should be the goal. [ABSTRACT FROM AUTHOR]

Aims: Not all patients with heart failure with reduced ejection fraction (HFrEF) benefit equally from beta‐blockers. Previous studies suggest that myocardial strain that reflects myocardial deformation may have a better prognostic value than the left ventricular ejection fraction. We aimed to evaluate the differential effect of beta‐blockers according to the global longitudinal strain (GLS) in patients with HFrEF. Methods and results: Of the 4312 patients in the Strain for Risk Assessment and Therapeutic Strategies in Patients with Acute Heart Failure registry, we included 2126 HFrEF patients whose data on beta‐blocker use and GLS were available. Patients were categorized into two groups: one group of patients had GLS ≥ 10%, and the other group had GLS < 10%. The primary outcome was 5 year all‐cause mortality according to beta‐blocker use. Of the 2126 patients with HFrEF, 526 (24.7%) and 1600 (75.3%) patients had GLS ≥ 10% and <10%, respectively. Overall, 1399 patients (65.8%) received beta‐blockers, and 864 (40.6%) patients died during the 5 year follow‐up. Beta‐blocker use was associated with improved survival in patients with GLS < 10% in both the inverse probability treatment‐weighted (hazard ratio 0.70, 95% confidence interval 0.59–0.83, P < 0.001) and Cox regression analyses (hazard ratio 0.69, 95% confidence interval 0.59–0.81; P < 0.001). However, beta‐blocker use was not associated with better survival in patients with GLS ≥ 10% in the inverse probability treatment‐weighted and Cox regression analyses (both P > 0.05). Conclusions: Beta‐blocker use appears to be associated with improved survival in patients with HFrEF and GLS < 10%, but this is not the case in patients with GLS ≥ 10%. Therefore, GLS may be used to identify patients who have attenuated benefits from beta‐blockers in HFrEF. Clinical Trial Registration: ClinicalTrials.gov: NCT03513653 (https://clinicaltrials.gov/ct2/show/NCT03513653). [ABSTRACT FROM AUTHOR]

Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2‐period randomized cross‐over design, MET was administered IV (0.04 mg/kg) and PO (6 mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non‐invasive blood pressure (NIBP). Blood samples were serially collected for 72 h post‐administration, and concentrations were determined by LC‐MS/MS. Pharmacokinetics were modeled using a 3‐compartment model and non‐linear least squares regression. Median (range) MET concentration was 110 (40.1–197) ng/ml collected 1 min (0.0167 h) after a bolus IV administration. Maximum concentration (Cmax) after PO administration was 2135 (1590–4170) ng/ml at 0.5 (0.25–0.5) hours. Oral bioavailability was 54% (17–100%). Median apparent volume of distribution was 0.39 (0.17–0.58) l/kg, clearance was 12.63 (11.41–18.94) ml/kg/min, and elimination half‐life was 21.1 (7.46–34.36) minutes. No clinically relevant effects of IV or PO metoprolol were noted on cardiac rhythm or NIBP. Sweating was the most common side effect. The metoprolol doses used in this study achieve plasma concentrations reported to achieve ß‐blockade in humans. [ABSTRACT FROM AUTHOR]

Aim: To compare risk algorithms (HCMRisk‐Kids, ECG Risk‐score) in hypertrophic cardiomyopathy (HCM) without syndrome association (ns‐HCM) and with Noonan‐like syndromes (RAS‐HCM). Methods: A national paediatric HCM cohort (n = 151), presenting <19 years of age, mean follow‐up 13.3 years, from all Swedish centres of Paediatric Cardiology (presenting 1972–2015), with 41 RAS‐HCM patients (61% males), and 110 ns‐HCM patients (68% familial; 65% males). The end‐point was a composite of sudden cardiac death and resuscitated cardiac arrest (SCD/CA). Risk‐factors were studied with Cox‐hazard regression, and receiver operating characteristic curve analysis (C‐statistic). Results: There were 33 SCD/CA, 27/110 in ns‐HCM and 6/41 in RAS‐HCM (p = 0.27). In ns‐HCM HCMRisk‐Kids ≥6% at diagnosis had C‐statistic of 0.69 for predicting SCD/CA during first 5 years of follow‐up and positive predictive value (PPV) of 22%. After 7 years of age (HCMRisk‐Kids7plus), C‐statistic was 0.76. ECG Risk‐score ≥6 at diagnosis had C‐statistic 0.87 and PPV of 31%. Independent risk factors for SCD/CA were HCMRisk‐Kids7plus score (p = 0.005) and ECG risk‐score (p < 0.001), whereas early beta‐blocker dose (p = 0.001) and myectomy (p = 0.004) reduced risk. The sum of HCMRisk‐Kids7yplus and ECG Risk‐score7yplus ≥14 best predicted SCD/CA within 5 years in ns‐HCM with C‐statistic of 0.90 [0.83–0.96], sensitivity 100% and PPV 38%. Conclusion: Combining the ECG Risk‐score with HCMRisk‐Kids improves risk stratification in ns‐HCM and shows promise in RAS‐HCM. [ABSTRACT FROM AUTHOR]

The number of patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) is increasing in Asia, and these conditions often coexist. We previously revealed a tendency of beta-blocker underuse among patients with HF with reduced ejection fraction (HFrEF) and COPD in Asian countries other than Japan. Here, we evaluated the impact of cardio-selective beta-blocker use on the long-term outcomes of patients with HF and COPD. Methods and results Among the 5232 patients with HFrEF (left ventricular ejection fraction of <40%) prospectively enrolled from 11 Asian regions in the ASIAN-HF registry, 412 (7.9%) had a history of COPD. We compared the clinical characteristics and long-term outcomes of the patients with HF and COPD according to the use and type of beta-blockers used: cardio-selective beta-blockers (n = 149) vs. non-cardio-selective beta-blockers (n = 124) vs. no beta-blockers (n = 139). The heart rate was higher, and the outcome was poorer in the no beta-blocker group than in the beta-blocker groups. The 2 year all-cause mortality was significantly lower in the non-cardio-selective beta-blocker group than in the no beta-blocker group. Further, the cardiovascular mortality significantly decreased in the non-cardio-selective beta-blocker group before (hazard ratio: 0.36; 95% confidence interval: 0.18–0.73; P = 0.004) and after adjustments (hazard ratio: 0.37; 95% confidence interval: 0.19–0.73; P = 0.005), but not in the cardio-selective beta-blocker group. Conclusions Beta-blockers reduced the all-cause mortality of patients with HFrEF and COPD after adjusting for age and heart rate, although the possibility of selection bias could not be completely excluded due to multinational prospective registry. [ABSTRACT FROM AUTHOR]

Aims: Use and dosing of guideline‐directed medical therapy (GDMT) in patients with heart failure (HF) have been shown to be suboptimal. Among new users of GDMT in HF, we followed the real‐life patterns of dose titration and discontinuation of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta‐blockers, mineralocorticoid receptor antagonists (MRA) and angiotensin receptor–neprilysin inhibitors (ARNI). Methods and results: New users were identified in health care databases in Sweden, UK and US between 2016–2019. Inclusion criterion was a recent HF hospitalization (HHF) triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta‐blocker, MRA and ARNI, and stratified by initial dose. Follow‐up was 12 months, until death or study end. Outcomes were dose titration within each drug class, discontinuation and first HHF or death. Dose/discontinuation follow‐up was assessed daily based on the coverage length of a filled prescription and reported on day 365. New users of ACEi (n = 8426), ARB (n = 2303), beta‐blockers (n = 10 476), MRA (n = 17 421), and ARNI (n = 29 546) were identified. Over 12 months, target dose achievement was 15%, 10%, 12%, 30%, and discontinuation was 55%, 33%, 24% and 27% for ACEi, ARB, beta‐blockers and ARNI, respectively. MRA was rarely titrated and discontinuation rates were high (40%). Event rates for HHF or death ranged from 40.0–86.9 per 100 patient‐years across the treatment groups. Conclusion: Despite high risk of clinical events following HHF, new initiation of GDMT was followed by consistent patterns of low up‐titration and early GDMT discontinuation in three countries with different health care and economies. Our data highlight the urgent need for moving away from long sequential approach when initiating HF treatment and for improving just‐in‐time decision support for patients and health care providers. [ABSTRACT FROM AUTHOR]

Background and purpose: Some groups of cardiovascular drugs (beta‐blocking drugs, Ca antagonists, antiarrhythmics) are listed as potentially worsening myasthenia. An empirical basis for alternative recommendations for antihypertensive and antiarrhythmic therapy in myasthenia patients has not yet been provided. Methods: From the World Health Organization pharmacovigilance database, we retrieved total and myasthenia‐related counts of adverse drug reactions for various groups of drugs used in cardiovascular disease and drugs with related mechanism of action used in other indications. We calculated the reporting odds ratio as a measure of a disproportional fraction of myasthenia‐related events among all events. A 95% confidence interval of reporting odds ratio (ROR) >1 was taken as an indication for a higher risk. Because our approach involves a considerable number of tests, this situation is referred to as a signal that requires additional confirmation. Results: A signal for an increased risk was noted for tizanidine, for alpha‐blocking drugs, for beta‐blocking drugs, and for Ca antagonists. ROR indicated a lower‐than‐average risk for salbutamol, angiotensin receptor antagonists, oral anticoagulants, thrombocytic function inhibitors, and heparins. Conclusions: Angiotensin receptor antagonists, angiotensin‐converting enzyme inhibitors, and diuretics seem to be safe in antihypertensive therapy. Surprisingly, and yet requiring confirmation by case reports, alpha receptor–blocking drugs seem to carry a risk of myasthenia worsening. Amiodarone seems to be a safe alternative in antiarrhythmic therapy in patients with myasthenia. [ABSTRACT FROM AUTHOR]

Background: There is controversy whether taking β‐blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β‐blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β‐blockers, 11.9% ACEI, 5.0% β‐blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of β‐blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p = 0.29). In total, 210 (17.7%) patients were re‐stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β‐blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β‐blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629). [ABSTRACT FROM AUTHOR]

Foundational therapy for heart failure and a reduced ejection fraction consists of a combination of an angiotensin receptor–neprilysin inhibitor, a beta‐blocker, a mineralocorticoid receptor antagonist and a sodium–glucose co‐transporter 2 (SGLT2) inhibitor. However, the conventional approach to the implementation is based on a historically‐driven sequence that is not strongly evidence‐based, typically requires ≥6 months, and frequently leads to major gaps in treatment. We propose a rapid sequencing strategy that is based on four principles. First, since drugs act rapidly to reduce morbidity and mortality, patients should be started on all four foundational treatments within 2–4 weeks. Second, since the efficacy of each foundational therapy is independent of treatment with the other drugs, priority can be determined by considerations of relative efficacy, safety and ease‐of‐use. Third, low starting doses of foundational drugs have substantial therapeutic benefits, and achievement of low doses of all four classes of drugs should take precedence over up‐titration to target doses. Fourth, since drugs can influence the tolerability of other foundational agents, sequencing can be based on whether agents started earlier can enhance the safety of agents started simultaneously or later in the sequence. We propose an accelerated three‐step approach, which consists of the simultaneous initiation of a beta‐blocker and an SGLT2 inhibitor, followed 1–2 weeks later by the initiation of sacubitril/valsartan, and 1–2 weeks later by a mineralocorticoid receptor antagonist. The latter two steps can be re‐ordered or compressed depending on patient circumstances. Rapid sequencing is a novel evidence‐based strategy that has the potential to dramatically improve the implementation of treatments that reduce the morbidity and mortality of patients with heart failure and a reduced ejection fraction. [ABSTRACT FROM AUTHOR]

Background: Achieving target doses of angiotensin‐converting‐enzyme inhibitor/angiotensin‐receptor blockers (ACEi/ARB) and beta‐blockers in heart failure with reduced ejection fraction (HFrEF) is often underperformed. In BIOlogy Study to TAilored Treatment in chronic heart failure (BIOSTAT‐CHF) study, many patients were not up‐titrated for which no clear reason was reported. Therefore, we hypothesized that perceived‐risk profile might influence treatment optimization. Methods: We studied 2100 patients with HFrEF (LVEF≤40%) to compare the clinical characteristics and adverse events associated with treatment up‐titration (after a 3‐month titration protocol) between; a) patients not reaching target doses for unclear reason; b) patients not reaching target doses due to symptoms and/or side effects; c) patients reaching target doses. Results: For ACEi/ARB, (a), (b) and (c) was observed in 51.3%, 25.9% and 22.7% of patients, respectively. For beta‐blockers, (a), (b) and (c) was observed in 67.5%, 20.2% and 12.3% of patients, respectively. By multinomial logistic regression analysis for ACEi/ARB, patients in group (a) and (b) had lower blood pressure and poorer renal function, and patients in group (a) were older and had lower ejection fraction. For beta‐blockers, patients in group (a) and (b) had more severe congestion and lower heart rate. At 9 months, adverse events (i.e., hypotension, bradycardia, renal impairment, and hyperkalemia) occurred similarly among the three groups. Conclusions: Patients in whom clinicians did not give a reason why up‐titration was missed were older and had more co‐morbidities. Patients in whom up‐titration was achieved did not have excess adverse events. However, from these observational findings, the pattern of subsequent adverse events among patients in whom up‐titration was missed cannot be determined. [ABSTRACT FROM AUTHOR]

Aims: Despite medical therapy for heart failure (HF) having proven benefits of improving quality of life and survival, many patients remain under‐treated. This may be due to a combination of under‐prescription by medical professionals and poor adherence from patients. In HF, as with many other chronic diseases, adherence to medication can deteriorate over time particularly when symptoms are well controlled. Therefore, detecting and addressing non‐adherence has a crucial role in the management of HF. Significant flaws and inaccuracies exist in the methods currently used to assess adherence such as patient reporting, pill counts, and pharmacy fill records. We aim to use high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS) to detect metabolites of HF medications in the urine samples of chronic HF patients. Methods and results: Urine samples were collected from 35 patients in a specialist HF clinic. Patients were included if they had an ejection fraction <45% and were taking at least two disease‐modifying HF medications. They were excluded if they had been admitted to hospital for HF in the 3 months preceding clinic attendance. These samples were sent for HPLC‐MS and tested for all HF medications prescribed for that patient. A high rate of complete adherence of 89% was detected in these patients, with 94% being partially adherent (at least one HF medication detected) to therapy (at least one HF medication detected). This analysis also highlighted that mineralocorticoid antagonists represent both the most under‐prescribed (67%) and poorly adhered (75%) medication class. Conclusions: This analysis revealed a surprisingly high level of adherence to disease‐modifying therapy in chronic HF patients and highlights that most of our 'total' under‐treatment is likely to be from a failure to prescribe rather than a failure to adhere. Testing for metabolites of disease‐modifying HF drugs in urine using HPLC‐MS is feasible and is a useful adjunct to a specialist HF service. At present, the distinction between treatment failure and failure to take treatment is not always clear, which is important because the investigation and potential solutions are different. The former needs initiation of additional therapies and consideration of additional diagnoses, whereas the latter requires strategies to understand reasons underlying poor adherence and collaborative working to improve this: the wrong strategy will be ineffective. [ABSTRACT FROM AUTHOR]

Background: Effective therapy for inappropriate sinus tachycardia (IST) remains challenging with high rates of treatment failure and symptom recurrence. It is uncertain how effective pharmacotherapy and procedural therapy are long‐term, with poor response to medical therapy in general. Methods: We retrospectively reviewed all patients with the diagnosis of IST at a tertiary academic medical center from 1998 to 2018. We extracted data related to prescribing patterns and symptom response to medical therapy and sinus node modification (SNM), assessing efficacy and periprocedural complication rates. Results: A total of 305 patients with a formal diagnosis of IST were identified, with 259 (84.9%) receiving at least one prescription medication related to the condition. Beta‐blockers were the most commonly used medication (n = 245), with a majority of patients reporting no change or worsening of symptoms, and poor response was seen to other medication classes. Improvement was seen significantly more often with ivabradine than beta blockers, though the sample size was limited (p =.003). Fifty‐five patients (18.0% of all IST patients), mean age 32.0 ± 9.1 years, underwent a SNM procedure, with an average of 1.8 ± 0.9 procedures per patient. Acute symptomatic improvement (<6 months) was seen in 58.2% of patients. Long‐term complete resolution of symptoms was seen in 5.5% of patients, modest improvement in 29.1%, and no long‐term benefit was seen in 65.5% of patients. Conclusions: Among all medical therapies, there were high rates of treatment failure or symptom worsening in over three‐quarters of patients in our study. Ivabradine was most beneficial, though the sample size was small. While most patients receiving SNM ablation for IST perceive an acute symptomatic improvement, almost two‐thirds of patients have no long‐term improvement, and resolution of symptoms is quite rare. AV node ablation with pacemaker implantation following lack of response to SNM offered increased success, though the sample size was limited. [ABSTRACT FROM AUTHOR]

Aim: It has been suggested that repeated activation of the adrenergic system during antecedent episodes of hypoglycaemia contributes to the development of counterregulatory failure. We previously reported that treatment with carvedilol, a non‐specific β‐blocker, prevented the development of counterregulatory failure and improved hypoglycaemia awareness in recurrently hypoglycaemic non‐diabetic rats. The current study investigated whether carvedilol has similar benefits in diabetic rats. Methods: Recurrently hypoglycaemic streptozotocin‐diabetic rats (STZ+RH) were treated with carvedilol for one week prior to undergoing a hypoglycaemic clamp. Hypoglycaemia awareness was evaluated in streptozotocin‐diabetic rats made hypoglycaemia unaware using repeated injections of 2‐deoxyglucose. Results: Compared to hypoglycaemia‐naïve STZ‐diabetic controls, exogenous glucose requirements were more than doubled in the STZ+RH animals and this was associated with a 49% reduction in the epinephrine response to hypoglycaemia. Treating STZ+RH animals with carvedilol improved the epinephrine response to hypoglycaemia. Of note, neither recurrent hypoglycaemia nor carvedilol treatment affected the glucagon response in diabetic animals. Additionally, carvedilol treatment improved the feeding response to insulin‐induced hypoglycaemia in diabetic animals made 'hypoglycaemia unaware' using repeated injections of 2‐deoxyglucose, suggesting the treatment improved awareness of hypoglycaemia as well. Conclusion: Our data suggest that carvedilol may be useful in preventing impairments of the sympathoadrenal response and the development of hypoglycaemia unawareness during recurring episodes of hypoglycaemia in diabetic animals. [ABSTRACT FROM AUTHOR]

Aims: Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up‐titration of angiotensin‐converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta‐blockers on outcome across the age spectrum in HFrEF patients. Methods and results: We analysed HFrEF patients on sub‐optimal doses of ACEI/ARB and/or beta‐blockers from the BIOSTAT‐CHF study stratified by age. Patients underwent a 3‐month up‐titration period. We used inverse probability weighting to adjust for the likelihood of successful up‐titration to determine the association of achieved dose with mortality and/or heart failure hospitalisation, testing for an interaction with age. Over a median follow‐up of 21 months in 1720 HFrEF patients (76.5% male, mean age 67 years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI/ARB and beta‐blocker achieved at 3 months were both significantly associated with reduced incidence of the primary outcome, [ACEI‐ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91–0.94, P < 0.001; beta‐blocker: HR 0.98, 95% CI 0.95–1.00, P = 0.046], with a significant interaction with age seen for beta‐blockers but not ACEI/ARB (P = 0.034 and P = 0.22, respectively). Conclusions: Achieving higher doses of ACEI/ARB was associated with improved outcome regardless of age. However, achieving higher doses of beta‐blockers was only associated with improved outcome in younger, but not in older patients. [ABSTRACT FROM AUTHOR]

This study sought to assess the prognostic impact of treatment with single beta‐blocker (BB) compared to combined therapy with BB plus amiodarone (BB‐AMIO) on recurrences of ventricular tachyarrhythmias in implantable cardioverter‐defibrillator (ICD) recipients. A large retrospective registry was used including consecutive ICD recipients with index episodes of ventricular tachyarrhythmias from 2002 to 2016. Patients treated with BB were compared to patients treated with BB‐AMIO. Kaplan‐Meier and Cox regression analyses were applied for the evaluation of the primary end‐point defined as first recurrences of ventricular tachyarrhythmias at five years. Secondary end‐points comprised first appropriate ICD therapies, first cardiac rehospitalization and all‐cause mortality at five years. Among 512 ICD recipients, 81% were treated with BB and 19% with BB‐AMIO. BB and BB‐AMIO were associated with comparable risk of first recurrences of ventricular tachyarrhythmias (46% vs. 43%; log rank P =.941; HR = 1.013; 95% CI 0.725‐1.415; P =.941) and appropriate ICD therapies (35% vs. 37%; log rank P =.389; HR = 0.852; 95% CI 0.591‐1.228; P =.390). BB was associated with decreased long‐term all‐cause mortality within an univariable analysis only (20% vs. 28%; log rank p = 0.023). In conclusion, BB and BB‐AMIO were associated with comparable risks regarding recurrences of ventricular tachyarrhythmias at five years. [ABSTRACT FROM AUTHOR]

Beta‐2 adrenergic receptors are the only subgroup of beta‐adrenergic receptors expressed in the membrane of large cells, including skin keratinocytes, fibroblasts, and melanocytes. Alterations in the function or concentration of β2 adrenoreceptors related to keratinocytes are associated with some skin conditions. Some findings suggest the role of β2 adrenoreceptors in maintaining the function and integrity of the epidermis. Beta‐receptor antagonists can be systemically and topically effective in healing hemangioma, paronychia, vasculitis ulcer, tufted angioma, acute and chronic wounds. Most studies with a strong design on this subject deal with the systemic form, but recently, numerous case and group reports and smaller studies have focused on topical forms, especially topical timolol. The present comprehensive review study surveys the role of topical timolol in acute and chronic wound healing in the field of dermatology. [ABSTRACT FROM AUTHOR]

Donepezil toxicity can present similarly to beta‐blocker overdose and colitis. Symptoms include confusion, diaphoresis, and bradycardia. In patients with suspected medication‐related toxicities, it is important to consider all possible causative agents in the active medication list. [ABSTRACT FROM AUTHOR]

Organophosphorus (OP) compounds are chemical threat agents and are irreversible inhibitors of the enzyme acetylcholinesterase that lead to a hypercholinergic response that could include status epilepticus (SE). SE particularly targets the heart and brain and despite existing therapies, it is still associated with significant mortality and morbidity. Here, we investigated the effect of intramuscular (i.m.) adjunct therapy consisting of atenolol (AT) and levetiracetam (LV) when administered after paraoxon (POX)‐induced SE. The combination therapy was administered twice daily for 2, 7, or 14 days. POX exposure in rats produced rapid SE onset that was treated with atropine, pralidoxime chloride, and midazolam. Here, AT + LV therapy produced significant reductions in POX SE mortality assessed at 30 days post‐SE. AT + LV therapy exhibited muscle pathology inflammation scores that were not significantly different from saline‐treated controls. Pharmacokinetic analyses revealed that the i.m. route achieved faster and stabler plasma therapeutic levels for both AT and LV under OP SE conditions compared with oral administrations. Our data provide evidence of the safety and efficacy of i.m. AT + LV therapy for reducing mortality following POX SE. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: To examine the association between hospitalization for a fall‐related injury and the co‐prescription of a cholinesterase inhibitor (ChEI) among persons with dementia receiving a beta‐blocker, and whether this potential drug‐drug interaction is modified by frailty. DESIGN: Nested case‐control study using population‐based administrative databases. SETTING: All nursing homes in Ontario, Canada. PARTICIPANTS: Persons with dementia aged 66 and older who received at least one beta‐blocker between April 2013 and March 2018 following nursing home admission (n = 19,060). MEASUREMENTS: Cases were persons with dementia with a hospitalization (emergency department visit or acute care admission) for a fall‐related injury with concurrent beta‐blocker use. Each case (n = 3,038) was matched 1:1 to a control by age (±1 year), sex, cohort entry year, frailty, and history of fall‐related injuries. The association between fall‐related injury and exposure to a ChEI in the 90 days prior was examined using multivariable conditional logistic regression. Secondary exposures included ChEI type, daily dose, incident versus prevalent use, and use in the prior 30 days. Subgroup analyses considered frailty, age group, sex, and history of hospitalization for fall‐related injuries. RESULTS: Exposure to a ChEI in the prior 90 days occurred among 947 (31.2%) cases and 940 (30.9%) controls. In multivariable models, no association was found between hospitalization for a fall‐related injury and prior exposure to a ChEI in persons with dementia dispensed beta‐blockers (adjusted odds ratio =.96, 95% confidence interval =.85–1.08). Findings were consistent across secondary exposures and subgroup analyses. CONCLUSION: Among nursing home residents with dementia receiving beta‐blockers, co‐prescription of a ChEI was not associated with an increased risk of hospitalization for a fall‐related injury. However, we did not assess for its association with falls not leading to hospitalization. This finding could inform clinical guidelines and shared decision making between persons with dementia, caregivers, and clinicians concerning ChEI initiation and/or discontinuation. [ABSTRACT FROM AUTHOR]

Aims: Current guidelines recommend beta‐blocker therapy in chronic heart failure with reduced ejection fraction (HFrEF) titrated according to tolerated target dose. The efficiency of this strategy to obtain adequate heart rate (HR) control remains unclear in clinical practice. The aim of this study was to determine, in a real‐world setting, the proportion of HFrEF patients who fail to achieve beta‐blocker target doses, whether target doses of beta‐blockers have a relationship with the adequacy in reducing resting HR over time. Methods and results: Beta‐blocker dose and resting HR of consecutive ambulatory patients with a diagnosis of HFrEF (ejection fraction ≤ 35%) in sinus rhythm were reviewed at the first outpatient contact in the Cleveland Clinic Health System from the year 2000 to 2015. Patients who did not receive beta‐blocker therapy, have congenital heart disease and hypertrophic cardiomyopathy, were not in sinus rhythm, or have a history of heart transplant were excluded. Patients were followed up until their last known visit at the Cleveland Clinic. Median resting HR was 71 b.p.m. [inter‐quartile range (IQR) 60–84 b.p.m.] in 8041 patients (median age 65; 68% male) with 67% on carvedilol, 32% on metoprolol succinate, and 1% on bisoprolol. In 3674 subjects (56%), resting HR was ≥70 b.p.m. At final follow‐up after a median of 21 months (IQR 0.1–7.2 years), resting HR was 72 b.p.m. (IQR 60–84 b.p.m.) in the subset of patients with persistently low ejection fraction ≤ 35%. HR ≥ 70 b.p.m. was observed in 55% of this group. Beta‐blocker target dose was achieved in 19%, 5%, and 15% of those receiving carvedilol, metoprolol succinate, and bisoprolol, respectively. In the subset of patients who experienced beta‐blocker up‐titration, reduced mortality or hospitalization due to heart failure was observed in patients who experienced the lowest HR after titration. Conclusions: In our single‐centre experience, the majority of patients with chronic HFrEF treated with beta‐blocker therapy did not achieve target doses over time, and a substantial proportion had inadequate control of resting HR. There was no relationship between achieved beta‐blocker target dose and resting HR control. [ABSTRACT FROM AUTHOR]

While patients with acute heart failure often have tachycardia with atrial fibrillation, there have been no established medical tools that control tachycardia safely and definitely. Digoxin has been recommended as a first choice in the former guidelines, but it takes time to affect and has a risk of adverse events particularly for those with chronic kidney disease. Landiolol is a recently innovated ultra‐short‐acting beta‐blocker with 251‐fold β1/β2 selectivity, which was originally indicated only to control peri‐operative supra‐ventricular tachyarrhythmia by 2013 in Japan. We aimed to review how to use landiolol in patients with cardiac dysfunction and tachycardia due to atrial fibrillation. We reviewed recently conducted randomized control trials using landiolol, recently updated guidelines, as well as current practical use of landiolol. Japan landiolol vs. Digoxin (J‐Land) study demonstrated that landiolol was more effective to control tachycardia than digoxin in atrial fibrillation patients with left ventricular dysfunction in 2013. Given the result, the revised Japanese heart failure guideline recommends landiolol for rate control during atrial fibrillation in acute heart failure patients as Class IIa with evidence level B. Currently in Japan, landiolol is used for rate control, even in patients with advanced heart failure receiving continuous infusion of inotropes. The clinical use of landiolol in patients with cardiac dysfunction and tachycardia due to atrial fibrillation is increasing. Further studies are warranted to investigate the implication of faster and safer rate control using landiolol. [ABSTRACT FROM AUTHOR]

Low blood pressure is common in patients with heart failure and reduced ejection fraction (HFrEF). While spontaneous hypotension predicts risk in HFrEF, there is only limited evidence regarding the relationship between hypotension observed during heart failure (HF) drug titration and outcome. Nevertheless, hypotension (especially orthostatic hypotension) is an important factor limiting the titration of HFrEF treatments in routine practice. In patients with signs of shock and/or severe congestion, hospitalization is advised. However, in the very frequent cases of non-severe and asymptomatic hypotension observed while taking drugs with a class I indication in HFrEF, European and US guidelines recommend maintaining the same drug dosage. In instances of symptomatic or severe persistent hypotension (systolic blood pressure < 90 mmHg), it is recommended to first decrease blood pressure reducing drugs not indicated in HFrEF as well as the loop diuretic dose in the absence of associated signs of congestion. Unless the management of hypotension appears urgent, a HF specialist should then be sought rather than stopping or decreasing drugs with a class I indication in HFrEF. If symptoms or severe hypotension persist, no recommendations exist. Our HF group reviewed available evidence and proposes certain steps to follow in such situations in order to improve the pharmacological management of these patients. [ABSTRACT FROM AUTHOR]

Background: Beta-blockers reduce mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). However, patients older than 80 years are poorly represented in randomized controlled trials. We assessed the association between beta-blocker use and outcomes in HFrEF patients aged ≥80 years.Methods and Results: We included patients with an ejection fraction <40% and aged ≥80 years from the Swedish HF Registry. The association between beta-blocker use, all-cause mortality and cardiovascular (CV) mortality/HF hospitalization was assessed by Cox proportional hazard models in a 1:1 propensity score-matched cohort. To assess consistency, the same analyses were performed in a positive control cohort with age <80 years. A negative control outcome analysis was run using hospitalization for cancer as endpoint. Of 6562 patients aged ≥80 years, 5640 (86%) received beta-blockers. In the matched cohort including 1732 patients, beta-blocker use was associated with a significant reduction in the risk of all-cause mortality [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.79-0.99]. Reduction in CV mortality/HF hospitalization was not significant (HR 0.94, 95% CI 0.85-1.05) due to the lack of association with HF hospitalization, whereas CV death was significantly reduced. After adjustment rather than matching for the propensity score in the overall cohort, beta-blocker use was associated with reduced risk of all outcomes. In patients aged <80 years, use of beta-blockers was associated with reduced risk of all-cause death (HR 0.79, 95% CI 0.68-0.92) and of the composite outcome (HR 0.88, 95% CI 0.77-0.99).Conclusions: In HFrEF patients ≥80 years of age, use of beta-blockers was high and was associated with improved all-cause and CV survival. [ABSTRACT FROM AUTHOR]

Background: Clinical variables that predict long‐term mortality and recurrence of Takotsubo syndrome (TTS) are not completely understood as the role of acquired corrected QT interval (QTc) prolongation. Aim: To detect the prevalence of QTc interval prolongation in patients with TTS and to evaluate its long‐term prognostic impact. Methods: QTc intervals were analysed in 105 patients presenting with symptoms of TTS. These patients were included in an ongoing retrospective cohort database. The cohort was subsequently subdivided into two groups based on the presence (long QT (LQT) group, n = 73, 69.52%) or absence (non‐long QT (non‐LQT) group, n = 32, 30.43%) of QTc interval prolongation. Patients were followed up over a mean period of 4.2 years. The rate of life‐threatening arrhythmia during the first 30 days in the LQT group was comparable with the non‐LQT group (10.9 vs 12.5%), whereas in‐hospital mortality and 30‐day mortality occurred less frequently in the LQT group (2.7 vs 18.75%, P < 0.01). Results: During this time span, 17 (23.3%) patients with acquired LQT syndrome died, whereas 14 (43.7%) patients with non‐LQT duration died. Kaplan–Meier survival rates were significantly higher in the LQT group than those in the non‐LQT group (Log‐rank‐test, P = 0.02). On multivariate analysis, the QTc interval was an independent negative predictor of all‐cause mortality (P = 0.02). Conclusion: The QTc interval at admission is an independent negative predictor of long‐term adverse outcome in patients with TTS. [ABSTRACT FROM AUTHOR]

β‐Cardiotoxin is a novel member of the snake venom three‐finger toxin (3FTX) family. This is the first exogenous protein to antagonize β‐adrenergic receptors and thereby causing reduction in heart rates (bradycardia) when administered into animals, unlike the conventional cardiotoxins as reported earlier. 3FTXs are stable all β‐sheet peptides with 60–80 amino acid residues. Here, we describe the three‐dimensional crystal structure of β‐cardiotoxin together with the identification of a molten globule intermediate in the unfolding pathway of this protein. In spite of the overall structural similarity of this protein with conventional cardiotoxins, there are notable differences observed at the loop region and in the charge distribution on the surface, which are known to be critical for cytolytic activity of cardiotoxins. The molten globule intermediate state present in the thermal unfolding pathway of β‐cardiotoxin was however not observed during the chemical denaturation of the protein. Interestingly, circular dichroism (CD) and NMR studies revealed the presence of α‐helical secondary structure in the molten globule intermediate. These results point to substantial conformational plasticity of β‐cardiotoxin, which might aid the protein in responding to the sometimes conflicting demands of structure, stability, and function during its biological lifetime. PDB Code(s): 3PLC; [ABSTRACT FROM AUTHOR]

Metoprolol {systematic name: (RS)‐1‐isopropylamino‐3‐[4‐(2‐methoxyethyl)phenoxy]propan‐2‐ol}, C15H25NO3, is a cardioselective β1‐adrenergic blocking agent that shares part of its molecular skeleton with a large number of other β‐blockers. Results from its solid‐state characterization by single‐crystal and variable‐temperature powder X‐ray diffraction and differential scanning calorimetry are presented. Its molecular and crystal arrangements have been further investigated by molecular modelling, by a Cambridge Structural Database (CSD) survey and by Hirshfeld surface analysis. In the crystal, the side arm bearing the isopropyl group, which is common to other β‐blockers, adopts an all‐trans conformation, which is the most stable arrangement from modelling data. The crystal packing of metoprolol is dominated by an O—H...N/N...H—O pair of hydrogen bonds (as also confirmed by a Hirshfeld surface analysis), which gives rise to chains containing alternating R and S metoprolol molecules extending along the b axis, supplemented by a weaker O...H—N/N—H...O pair of interactions. In addition, within the same stack of molecules, a C—H...O contact, partially oriented along the b and c axes, links homochiral molecules. Amongst the solid‐state structures of molecules structurally related to metoprolol deposited in the CSD, the β‐blocker drug betaxolol shows the closest analogy in terms of three‐dimensional arrangement and interactions. Notwithstanding their close similarity, the crystal lattices of the two drugs respond differently on increasing temperature: metoprolol expands anisotropically, while for betaxolol, an isotropic thermal expansion is observed. The metoprolol free base has been characterized in the solid state by X‐ray diffaction (both single‐crystal and variable‐temperature powder diffraction) and differential scanning calorimetry. These studies are supplemented by molecular modelling and Hirshfeld surface analysis. Structural relationships with the strictly related betaxolol are discussed. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: The purpose of this study was to evaluate the association between early β‐blocker continuation and major inpatient events in patients hospitalized for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This single centre, retrospective, investigational review board approved cohort study evaluated patients admitted for a primary diagnosis of AECOPD. Patients were evaluated based on early continuation of a β‐blocker whether a β‐blocker was initiated within 24 hours of admission and continued for at least 72 hours. Patients with AECOPD who did not receive β‐blockers were assigned to the control group. Major inpatient events were a composite outcome composed of arrhythmias, myocardial infarction (MI) and death. Safety data were collected on the incidences of bradycardia, bronchospasms and hypotension. Results and discussion: Of the 96 patients admitted for AECOPD, fifty‐five patients were included in the early β‐blocker group and forty‐one patients in the control group. Early β‐blocker utilization was associated with a significantly lower rate of major inpatient events compared with the control group (40% vs 80.5%; P < 0.001). Arrhythmias were significantly less common in the early β‐blocker group (30.9% vs 65.9%; P = 0.001); however, there were no significant differences in the rates of MI (9.1% vs 14.6%; P = 0.54), death (0 vs 0) or safety outcomes between groups. What is new and conclusion: β‐blocker therapy could result in a paradigm shift in managing chronic obstructive pulmonary disease patients from a true cardiopulmonary approach. This retrospective cohort study demonstrated early β‐blocker continuation in patients admitted for an AECOPD was associated with less major inpatient events, primarily arrhythmias. [ABSTRACT FROM AUTHOR]

Background: Recommendations on contraindications to allergen immunotherapy (AIT) have been independently developed by National and International Societies/Academies. AIT contraindications are mainly based on case reports, case‐series, or experts' opinion, while evidence‐based information is limited. The aim of the present review was to describe existing guidelines on contraindications to AIT and to highlight differences between them. Main body: An extended review of the literature regarding contraindications to AIT for respiratory allergy and venom hypersensitivity was performed. Furthermore, Societies and Academies registered in the World Allergy Organization and EAACI databases, were asked for additional information. Only AIT guidelines published under official auspicies were included. A large heterogeneity among the various recommendations on contraindications was registered. Common contraindications to most of the guidelines were: lack of adherence, pregnancy before the start of AIT, the use of beta‐blockers, certain age groups, uncontrolled asthma, autoimmune diseases and malignancies. Conclusion: As new data arise, revisions might soon be needed allowing AIT in the cases of patients treated with ACE inhibitors and beta‐blockers, in elderly patients and in patients with concomitant autoimmune diseases and neoplasias in remission. The decision to prescribe AIT is always tailor‐made, balancing risk vs benefit. Creating globally accepted guidelines would help Allergologists in their decision making. [ABSTRACT FROM AUTHOR]

Introduction: Beta‐blockers are indicated for secondary prevention of coronary artery disease (CAD). However, in patients with co‐morbidity of chronic obstructive pulmonary disease (COPD) an underuse of beta‐blocker has been reported. Materials and Methods: Prescription and demographic data and information on hospital discharge diagnoses from 13 Austrian health insurance funds for the years 2006‐2007 were analyzed. The primary end point was all‐cause mortality of patients with CAD with or without COPD and its association with use of beta‐blockers. Results: In 2006 and 2007, 65717 patients (37% female, 63% male) were discharged with a diagnosis of CAD. Among these patients, 46% had a co‐diagnosis of COPD, 24% had diabetes, and 75% received beta‐blockers. Use of beta‐blockers was comparable in CAD patients with COPD and without COPD with 77% and 74%, respectively. Thousand eight hundred seventy‐two (8.1%) and 1473 (5.6%) patients with and without COPD, who used beta‐blockers died within months in 2006 and 2007. Thousand five hundred fifty‐three (22.0%) and 1862 (22.2%) of patients with and without COPD and without beta‐blockers died during the corresponding time period. Discussion: Use of beta‐blockers was similar in patients with CAD with or without co‐diagnosis of COPD. However, mortality of beta‐blocker users was markedly lower than that of nonusers in patients with CAD with or without COPD. [ABSTRACT FROM AUTHOR]

Beta-blockers are one of the most commonly prescribed classes of antihypertensive medications during pregnancy. Previous studies reported an association between beta-blocker exposure and intrauterine growth restriction. Whether some beta-blocker subtypes may be associated with higher risk is not known. This is a retrospective cohort study of pregnant women exposed to beta-blockers in the Kaiser Permanente Southern California Region between 2003 and 2014. Logistic regression models were used to evaluate association between exposure to different beta-blocker agents and risk of low fetal birth weights. In a cohort of 379 238 singleton pregnancies, 4847 (1.3%) were exposed to beta-blockers. The four most commonly prescribed beta-blockers were labetalol (n = 3357), atenolol (n = 638), propranolol (n = 489), and metoprolol (n = 324). Mean birth weight and % low birth weight (<2500 g) were 2926 ± 841 g and 24.4% for labetalol, 3058 ± 748 g and 18.0% for atenolol, 3163 ± 702 g and 13.3% for metoprolol, 3286 ± 651 g and 7.6% for propranolol, and 3353 ± 554 g and 5.2% for non-exposed controls. Exposure to atenolol and labetalol were associated with increased risks of infant born small for gestational age (SGA) (atenolol: adjusted OR 2.4, 95% CI: 1.7-3.3; labetalol: adjusted OR 2.9, 95% CI: 2.6-3.2). Risk of SGA associated with metoprolol or propranolol exposure was not significantly different from the non-exposed group (metoprolol: adjusted OR 1.5, 95% CI: 0.9-2.3; propranolol: adjusted OR 1.3, 95% CI: 0.9-1.9). Association between beta-blocker exposure and SGA does not appear to be a class effect. Variations in pharmacodynamics and confounding by indication may explain these findings. [ABSTRACT FROM AUTHOR]