Effect of beta-blockade on mortality in patients with cardiac amyloidosis: A systematic review and meta-analysis.

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.

Maintenance of beta-blockers and cardiac surgery-related outcomes: a prospective propensity-matched multicentre analysis.

BACKGROUND: We investigated the effects of maintaining beta-blockers on the day of surgery on the incidence of atrial fibrillation and postoperative acute kidney injury (AKI) in patients undergoing cardiac surgery. METHODS: We conducted a multicentre prospective observational study with propensity matching on patients treated with beta-blockers. We collected their baseline patient characteristics, comorbidities, and operative and postoperative outcomes. The endpoints were postoperative atrial fibrillation and AKI after cardiac surgery. RESULTS: Of the 1789 included patients, propensity matching led to 583 patients in each group. Maintenance of beta-blockers was not associated with a reduced risk of atrial fibrillation (odds ratio: 0.86 [95% confidence interval 0.66-1.14], P=0.335; 141 patients [24.2%] vs 126 patients [21.6%]). Sensitivity analysis did not demonstrate association between beta-blocker maintenance and atrial fibrillation after cardiac surgery (odds ratio: 0.93 [95% confidence interval: 0.72-1.22], P=0.625). Maintenance of beta-blockers was associated with a higher rate of norepinephrine use (415 [71.2%] vs 465 [79.8%], P=0.0001) and postoperative AKI (124 [21.3%] vs 159 [27.3%], P=0.0127). No statistically significant difference was observed in ICU length of stay. CONCLUSIONS: Maintenance of beta-blockers on the day of surgery was not associated with a reduced incidence of postoperative atrial fibrillation. However, maintenance of beta-blockers was associated with increased usage of vasopressors, potentially contributing to adverse postoperative renal events. CLINICAL TRIAL REGISTRATION: NCT04769752.

Association of preoperative beta-blocker use and cardiac complications after major noncardiac surgery: a prospective cohort study.

INTRODUCTION: Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear. METHODS: In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery. Cardiac complications were prospectively monitored and centrally adjudicated by two independent experts. The primary endpoint was perioperative myocardial infarction or injury attributable to a cardiac cause (cardiac PMI) within the first three postoperative days. The secondary endpoints were major adverse cardiac events (MACE), defined as a composite of myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death and all-cause death after 365 days. We used inverse probability of treatment weighting to account for differences between patients receiving beta-blockers and those who did not. RESULTS: A total of 3839/10 272 (37.4%) patients (mean age 74 yr; 44.8% female) received beta-blockers before surgery. Patients on beta-blockers were older, and more likely to be male with established cardiorespiratory and chronic kidney disease. Cardiac PMI occurred in 1077 patients, with a weighted odds ratio of 1.03 (95% confidence interval [CI] 0.94-1.12, P=0.55) for patients on beta-blockers. Within 365 days of surgery, 971/10 272 (9.5%) MACE had occurred, with a weighted hazard ratio of 0.99 (95% CI 0.83-1.18, P=0.90) for patients on beta-blockers. CONCLUSION: Preoperative use of beta-blockers was not associated with decreased cardiac complications including cardiac perioperative myocardial infarction or injury and major adverse cardiac event. Additionally, preoperative use of beta-blockers was not associated with increased all-cause death within 30 and 365 days. CLINICAL TRIAL REGISTRATION: NCT02573532.

The effect of concomitant beta-blocker use on survival in patients with metastatic renal cell carcinoma treated with a vascular endothelial growth factor receptor inhibitors in the first line.

PURPOSE: Vascular endothelial growth factor (VEGF) inhibition is one of the cornerstones of treatment in the treatment of metastatic renal cell carcinoma (mRCC). Since RCC is a disease of advanced age and hypertension as a side effect of VEGF receptor inhibitors, beta-blocker use is common in these patients. We aimed to compare the treatment efficacy and survival results in case of concomitant use of these two drugs due to the inhibition of VEGF in beta-blockers. METHODS: A total of 121 patients with a diagnosis of mRCC who used sunitinib or pazopanib in first-line therapy were included in the study. These patients were divided into two groups as those using concomitant beta-blockers and those not using them. RESULT: The median overall survival (mOS) of the patient using sunitinib or pazopanib and concomitant beta-blocker was 47 (95% CI 29.0-65.0) months, and the mOS of those not using concomitant beta-blocker was 18 (95% CI 8.9-27.1) months (p < 0.001). The median progression-free survival (mPFS) of the patients using sunitinib or pazopanib and concomitant beta-blocker was 20.4 (95% CI 4.5-40.1) months, and the mPFS of those not using it was 11.4 (95% CI 5.9-16.9) months (p = 0.042). Concomitant beta-blocker use was found to be a good prognostic factor for OS in the multivariate analysis (p = 0.029). In the multivariate analysis, concomitant beta-blocker use had a trend towards statistical significance for PFS (p = 0.062). CONCLUSION: Concomitant use of betablockers with sunitinib or pazopanib is associated with longer overall survial and progression free survival.

Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.

Influence of a chronic beta-blocker therapy on perioperative opioid consumption - a post hoc secondary analysis.

BACKGROUND: Beta-blocker (BB) therapy plays a central role in the treatment of cardiovascular diseases. An increasing number of patients with cardiovascular diseases undergoe noncardiac surgery, where opioids are an integral part of the anesthesiological management. There is evidence to suggest that short-term intravenous BB therapy may influence perioperative opioid requirements due to an assumed cross-talk between G-protein coupled beta-adrenergic and opioid receptors. Whether chronic BB therapy could also have an influence on perioperative opioid requirements is unclear. METHODS: A post hoc analysis of prospectively collected data from a multicenter observational (BioCog) study was performed. Inclusion criteria consisted of elderly patients (≥ 65 years) undergoing elective noncardiac surgery as well as total intravenous general anesthesia without the use of regional anesthesia and duration of anesthesia ≥ 60 min. Two groups were defined: patients with and without BB in their regular preopreative medication. The administered opioids were converted to their respective morphine equivalent doses. Multiple regression analysis was performed using the morphine-index to identify independent predictors. RESULTS: A total of 747 patients were included in the BioCog study in the study center Berlin. 106 patients fulfilled the inclusion criteria. Of these, 37 were on chronic BB. The latter were preoperatively significantly more likely to have arterial hypertension (94.6%), chronic renal failure (27%) and hyperlipoproteinemia (51.4%) compared to patients without BB. Both groups did not differ in terms of cumulative perioperative morphine equivalent dose (230.9 (BB group) vs. 214.8 mg (Non-BB group)). Predictive factors for increased morphine-index were older age, male sex, longer duration of anesthesia and surgery of the trunk. In a model with logarithmised morphine index, only gender (female) and duration of anesthesia remained predictive factors. CONCLUSIONS: Chronic BB therapy was not associated with a reduced perioperative opioid consumption. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT02265263 ) on the 15.10.2014 with the principal investigator being Univ.-Prof. Dr. med. Claudia Spies.

Effect of metoprolol in hypertrophic obstructive cardiomyopathy patients after alcohol septal ablation.

Background: The use of beta-blockers in hypertrophic obstructive cardiomyopathy (HOCM) patients after alcohol septal ablation (ASA) lacks data support. We aimed to evaluate the effect of metoprolol on exercise capacity, hemodynamic and laboratory parameters, and quality of life in HOCM patients after ASA. Methods: This was a prospective randomized single-center open-label crossover trial in 21 HOCM patients after ASA. Patients received metoprolol and no beta-blocker for two periods of three months. The endpoints were: peak oxygen uptake (pVO2), maximal left ventricular outflow tract (LVOT) pressure gradient at peak exercise, a ratio of mitral peak velocity of the early filling (E) to early diastolic mitral annular velocity (e') (E/e') at rest, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) plasmatic concentration. Results: No significant association was found between the treatment and any of the endpoints in the assessed patients: 1) pVO2 (19.5 ± 5.3 ml/kg/min vs. 19.4 ± 4.1 ml/kg/min, p = 0.90), 2) exercise-induced pressure gradient in LVOT 32 ± 37 mmHg vs. 32 ± 30 mmHg, p = 0.84, 3) E/e' ratio at rest (11 ± 4 vs. 10 ± 4, p = 0.23), 4) KCCQ overall summary score (78 ± 11 vs. 77 te ± 15, p = 0.56), 5) NT-proBNP (215 pg/ml [121-333] vs. 153 pg/ml [102-228], p = 0.19). Conclusions: In HOCM patients after successful ASA, metoprolol treatment did not improve exercise capacity, hemodynamic and laboratory parameters, or quality of life.

El papel de la Ivabradina y la titulación de los betabloqueadores en la insuficiencia cardíaca: una serie de casos y revisión de la literatura / The role of Ivabradine and beta-blocker titration in heart failure: a case series and literature review

RESUMEN Introducción y objetivos : La insuficiencia cardíaca (IC) es una preocupación creciente de salud pública. Si bien los betabloqueantes (BB) son la base del tratamiento, lograr reducciones objetivo de frecuencia cardíaca puede ser difícil debido a los efectos secundarios y la tolerancia limitada. La ivabradina, un inhibidor único de la corriente If, ofrece un enfoque complementario para controlar la frecuencia cardíaca sin afectar la contractilidad. El objetivo de este estudio fue evaluar la eficacia de agregar ivabradina a la terapia BB en pacientes con IC. Métodos: Se realizó un estudio observacional retrospectivo en un hospital privado en San José, Costa Rica se analizaron 7 casos de pacientes tratados con BB a los cuales posteriormente se les adicionó ivabradina. Se recopilaron datos demo- gráficos, las características clínicas, la frecuencia cardíaca previa y posterior a la ivabradina, la clase funcional NYHA y los valores de laboratorio seleccionados. Resultados: La ivabradina redujo significativamente la frecuencia cardíaca en reposo en un promedio de 26,87 latidos por minuto. El 42,86% alcanzó la dosis meta de su BB inicial después de agregar ivabradina. La clase funcional NYHA se mantuvo estable o mejoró en todos los casos. Conclusiones: Estos resultados sugieren que agregar ivabradina a la terapia BB puede ser una estrategia eficaz para optimizar el control de la frecuencia cardíaca en pacientes con IC. Este enfoque puede mejorar la tolerabilidad de BB, lo que lleva a un mayor manejo de la dosis meta y posiblemente mejores resultados clínicos.

ABSTRACT Introduction and objectives: Heart failure (HF) is a growing public health concern. While beta-blockers (BBs) are the cornerstone of treatment, achieving target heart rate reductions can be difficult due to side effects and limited tolerance. Ivabradine, a unique inhibitor of the If current, offers a complementary approach to controlling heart rate without affecting contractility. This study aimed to evaluate the effectiveness of adding ivabradine to BB therapy in patients with HF. Methods : A retrospective observational study was conducted at a private hospital in San José, Costa Rica. Seven cases of patients treated with BBs who were subsequently added to ivabradine were analyzed. Demographic data, clinical characteristics, heart rate before and after ivabradine, NYHA functional class, and selected laboratory values were collected. Results : Ivabradine significantly reduced resting heart rate by an average of 26.87 beats per minute. Forty-two-point eight-six percent (42.86%) achieved the target dose of their initial BB after adding ivabradine. NYHA functional class remained stable or improved in all cases. Conclusions: These results suggest that adding ivabradine to BB therapy may be an effective strategy to optimize heart rate control in patients with HF. This approach may improve BB tolerability, leading to greater target dose management and possibly better clinical outcomes.

Effect of beta-blocker therapy on weight loss outcomes after sleeve gastrectomy & Roux-en-Y gastric bypass.

BACKGROUND: Patients taking beta-blockers (BBs) commonly experience weight gain. There is limited research exploring how BBs impact weight loss after bariatric surgery. OBJECTIVES: We examined how BBs impact 12-month weight loss in patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). SETTING: Large midwest health system. METHODS: We reviewed health records of SG and RYGB patients (2011-2022) and categorized them by BB usage (none, pre-, post-, or pre- and postoperative). Multivariable linear regression models examined the relation between BB use, percent total body weight loss (%TBWL), and percent excess body mass index lost (%EBMIL). RESULTS: A total of 889 individuals (SG, n = 485; RYGB, n = 404) had complete data. RYGB led to greater %TBWL compared to SG (31% versus 26%, P < .01) and greater %EBMIL (79% versus 64%, P < .01). BB status did not significantly affect 12-month %TBWL or %EBMIL. CONCLUSIONS: BB use may not significantly affect weight loss 12 months after bariatric surgery. This finding could enable physicians to prescribe BBs for improved blood pressure control in bariatric surgery patients with less concern of blunting weight loss. Longer term follow-up with a larger sample size would be an important next step to better characterize the relationship between BB usage and bariatric surgery.

Neurohumoral Activation in Heart Failure.

In patients with heart failure (HF), the neuroendocrine systems of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS) and the arginine vasopressin (AVP) system, are activated to various degrees producing often-observed tachycardia and concomitant increased systemic vascular resistance. Furthermore, sustained neurohormonal activation plays a key role in the progression of HF and may be responsible for the pathogenetic mechanisms leading to the perpetuation of the pathophysiology and worsening of the HF signs and symptoms. There are biomarkers of activation of these neurohormonal pathways, such as the natriuretic peptides, catecholamine levels and neprilysin and various newer ones, which may be employed to better understand the mechanisms of HF drugs and also aid in defining the subgroups of patients who might benefit from specific therapies, irrespective of the degree of left ventricular dysfunction. These therapies are directed against these neurohumoral systems (neurohumoral antagonists) and classically comprise beta blockers, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers and vaptans. Recently, the RAAS blockade has been refined by the introduction of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan, which combines the RAAS inhibition and neprilysin blocking, enhancing the actions of natriuretic peptides. All these issues relating to the neurohumoral activation in HF are herein reviewed, and the underlying mechanisms are pictorially illustrated.

A successful treatment with oral beta-blocker: A case report of a recurrent pyogenic granuloma in the external auditory canal.

Pyogenic granuloma or lobular capillary hemangioma is a vascular proliferation of the skin and mucosal surface, most commonly in the oral or nasal cavity. To the best of our knowledge, a few cases of auricular pyogenic granuloma were published in the literature. In our case, a 14-year-old female complained of a recurrent pyogenic granuloma in the external auditory canal that regressed successfully with the oral beta-blocker treatment.

Association of Discontinuing Preinjury Beta-Adrenergic Blockade Medications With Mortality in Severe Blunt Traumatic Brian Injury.

Background: Beta-adrenergic receptor blocker (BB) administration has been shown to improve survival after traumatic brain injury (TBI). However, studies to date that observe a benefit did not distinguish between continuation of preinjury BB versus de novo initiation of BB. Objectives: To determine the effect of continuation of preinjury BB and de novo initiation of BB on risk-adjusted mortality and complications for patients with TBI. Methods: Trauma quality collaborative data (2016-2021) were analyzed. Patients were excluded with hospitalization <48 hours, direct admission, or penetrating injury. Severe TBI was identified as a head abbreviated injury scale (AIS) value of 3 to 5. Patients were placed into 4 groups based on the preinjury BB use and administration of BB during hospitalization. Propensity score matching was used to create 1:1 matched cohorts of patients for comparisons. Odd ratios of mortality accounting for hospital clustering were calculated. A sensitivity analysis was performed excluding patients with AIS >2 injuries in all other body regions to create a cohort of isolated TBI patients. Results: A total of 15,153 patients treated at 35 trauma centers were available for analysis. Patients were divided into 4 cohort groupings related to preinjury BB use and postinjury receipt of BB. The odds of mortality was significantly reduced for patients with a TBI on a preinjury BB who had the medication continued in the acute setting (as compared with patients on preinjury BB who did not) (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.54-0.98; P = 0.04). Patients with a TBI who were not on preinjury BB did not benefit from de novo initiation of BB with regard to mortality (OR, 0.83; 95% CI, 0.64-1.08; P = 0.2). In the sensitivity analysis, excluding polytrauma patients, patients on preinjury BB who had BB continued had a reduction in mortality when compared with patients in which BB was stopped following a TBI (OR, 0.65; 95% CI, 0.47-0.91; P = 0.01). Conclusions: Continuing BB is associated with reduced odds of mortality in patients with a TBI on preinjury BB. We were unable to demonstrate benefit from instituting beta blockade in patients who are not on a BB preinjury.

Using administrative healthcare data to evaluate drug repurposing opportunities for cancer: the possibility of using beta-blockers to treat breast cancer.

Introduction: Cancer registries and hospital electronic medical records are commonly used to investigate drug repurposing candidates for cancer. However, administrative data are often more accessible than data from cancer registries and medical records. Therefore, we evaluated if administrative data could be used to evaluate drug repurposing for cancer by conducting an example study on the association between beta-blocker use and breast cancer mortality. Methods: A retrospective cohort study of women aged ≥50 years with incident breast cancer was conducted using a linked dataset with statewide hospital admission data and nationwide medication claims data. Women receiving beta blockers and first-line anti-hypertensives prior to and at diagnosis were compared. Breast cancer molecular subtypes and metastasis status were inferred by algorithms from commonly prescribed breast cancer antineoplastics and hospitalization diagnosis codes, respectively. Subdistribution hazard ratios (sHR) and corresponding 95% confidence intervals (CIs) for breast cancer mortality were estimated using Fine and Gray's competing risk models adjusted for age, Charlson comorbidity index, congestive heart failure, myocardial infraction, molecular subtype, presence of metastasis at diagnosis, and breast cancer surgery. Results: 2,758 women were hospitalized for incident breast cancer. 604 received beta-blockers and 1,387 received first-line antihypertensives. In total, 154 breast cancer deaths were identified over a median follow-up time of 2.7 years. We found no significant association between use of any beta-blocker and breast-cancer mortality (sHR 0.86, 95%CI 0.58-1.28), or when stratified by beta-blocker type (non-selective, sHR 0.42, 95%CI 0.14-1.25; selective, sHR 0.95, 95%CI 0.63-1.43). Results were not significant when stratified by molecular subtypes (e.g., triple negative breast cancer (TNBC), any beta blocker, sHR 0.16, 95%CI 0.02-1.51). Discussion: It is possible to use administrative data to explore drug repurposing opportunities. Although non-significant, an indication of an association was found for the TNBC subtype, which aligns with previous studies using registry data. Future studies with larger sample size, longer follow-up are required to confirm the association, and linkage to clinical data sources are required to validate our methodologies.

Trends of antihypertensive use among patients with cancer and hypertension in the United States 2002-2019.

Background: Hypertension (HTN) is the most frequently reported comorbidity in patients with malignancy. This study was conducted to assess the trend of different antihypertensive (AHT) medications used in cancer patients. Methods: We used the Medical Expenditure Panel Survey (MEPS) database from 2002 to 2019 to identify adult (age >18 years) cancer patients with HTN using appropriate International Classification of Disease (ICD)-9 and ICD-10 codes. Benign and uncertain neoplasms were excluded. P-trend values were calculated using weighted logistic regression with "year" as the predictor variable. Results: We identified ∼46 million adult hypertensive cancer patients with an increasing trend from 2002 to 2019 (3.3 m-6.7 m). Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) use in hypertensive cancer patients increased steadily, while diuretics and combined drugs decreased. Calcium channel blocker (CCB) use increased since 2014-15. In cancer patients with heart failure (HF), beta-blocker (BB) use increased; however, diuretic use peaked in 2014-15 and declined. The use of ACEi/ARB in cancer patients with Diabetes (DM) has increased, whereas BB, CCB, and diuretic use remained stable. Hypertensive cancer patients with Atherosclerotic Cardiovascular Disease (ASCVD) had increased ACEI/ARB use. Combination AHT use has decreased broadly. Conclusion: The ACEI/ARB and CCB use trends increased over the past two decades, whereas diuretics have declined. In cancer patients with DM or ASCVD, the use of ACEI/ARB is trending up. BB use showed an increasing trend in patients with HF. Combined AHT and diuretics use decreased. Total expenditure and out-of-pocket expenditure have a decreasing trend for all AHT medications.

ACEI/ARB and beta-blocker therapies for preventing cardiotoxicity of antineoplastic agents in breast cancer: a systematic review and meta-analysis.

Anthracyclines and trastuzumab are widely used to treat breast cancer but increase the risk of cardiomyopathy and heart failure. With the use of trastuzumab and anthracycline-containing medications, this study intends to evaluate the effectiveness and security of current treatments against cardiotoxicity. We conducted a systematic review of randomized controlled trials (RCTs), which used at least one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or beta-blocker (BB) to prevent cardiotoxicity of antineoplastic agents for breast cancer, in 4 databases (PubMed, Cochrane Library, EMBASE, Web of Science) from inception to 11 May 2022, without language restrictions. The outcome of interest was left ventricular ejection fraction (LVEF) and adverse events. Stata 15 and R software 4.2.1 were used to perform all statistical analyses. The Cochrane version 2 of the risk of bias tool was used to assess the risk of bias, and the grading of recommendations assessment, development, and evaluation (GRADE) assessment was used to appraise the quality of the evidence. Fifteen randomized clinical studies with a total of 1977 patients were included in the analysis. The included studies demonstrated statistically significant LVEF in the ACEI/ARB and BB treatment groups (χ2 = 184.75, I2 = 88.6%, p = 0.000; SMD 0.556, 95% CI 0.299 to 0.813). In an exploratory subgroup analysis, the benefit of experimental agents on LVEF, whether anthracyclines or trastuzumab, was prominent in patients treated with ACEIs, ARBs, and BBs. Compared to placebo, ACEI/ARB and BB treatments in breast cancer patients protect against cardiotoxicity after trastuzumab and anthracycline-containing medication treatment, indicating a benefit for both.

Survival outcomes of beta-blocker usage in HER2-positive advanced breast cancer patients: a retrospective cohort study.

Background: Clinical trials investigating the effects of beta-blockers (BBs) on cancer are underway. Evidence from preclinical research suggests that BBs could serve as anticancer agents and immune boosters. There is conflicting evidence regarding the effect of BB use on clinical outcomes in patients with breast cancer. Objectives: The study aimed to determine whether BB use is associated with progression-free survival (PFS) and overall survival (OS) in patients receiving anti-human epidermal growth factor receptor 2 (HER2) treatment for advanced breast cancer. Design: Retrospective hospital-based study. Methods: The participants enrolled were breast cancer patients with advanced HER2-positive status who initiated trastuzumab monotherapy or concomitant therapy with trastuzumab and any dose of BB. The patients were enrolled between January 2012 and May 2021 and divided into three groups based on whether they received a BB or not in the therapeutic regimen: BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+. PFS and OS were the primary and secondary endpoints, respectively. Results: The estimated median PFS in the BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+ groups was 51.93, 21.50, and 20.77 months, respectively. The corresponding OS was 56.70, 29.10, and 27.17 months. The intergroup differences in these durations were significant. Both PFS [adjusted hazard ratio (HR): 2.21, 95% confidence interval (CI): 1.56-3.12; p < 0.001]) and OS (adjusted HR: 2.46, 95% CI: 1.69-3.57; p < 0.001) were worse when BBs were used. Conclusion: Our study provides important evidence that BB use potentially has a negative effect on patients with HER2-positive advanced breast cancer. Nevertheless, despite the study's results, cardiovascular disease (CVD) should be appropriately treated in patients with HER2-positive advanced breast cancer. Other types of drugs can be used to treat CVD, but BB use should be avoided. Large real-world database and prospective studies should be conducted to validate the results of this study.

Use of beta-blockers for cancer therapy Summary: Background • Evidence from preclinical research suggests that beta-blockers (BBs) could serve as anticancer agents and immune boosters. • Beta-blockers could therefore be a potential therapy for cancers. • Trastuzumab is a drug that affects the overall survival (OS) and progression-free survival (PFS) of patients with HER2-positive breast cancer by binding to the extracellular domain of HER2. • This study investigates the effect of BBs on trastuzumab therapy in patients with advanced breast cancer. Method • This retrospective study was conducted between January 2012 and May 2021. • Patients with HER2-positive advanced breast cancer who were treated using trastuzumab monotherapy or trastuzumab concomitantly with any dose of a BB were recruited and divided into three groups. • One group received only the trastuzumab (BB−/trastuzumab+), another group received both BB+ (non-selective) and trastuzumab [BB+ (non-selective)/trastuzumab+], and the third group received both BB+ (selective) and trastuzumab [BB+ (selective)/trastuzumab+]. • The PFS and OS were determined and compared between the treatment groups. Results • We enrolled 221 patients (mean age: 56.1 ± 11.1 years) in the study. • The estimated median PFS and OS were significantly lower in the BB+ (non-selective)/trastuzumab+ and BB+ (selective)/trastuzumab+ groups than in the BB−/trastuzumab+ group. • The use of BBs was associated with worse PFS and OS in patients with HER2-positive advanced breast cancer. Conclusion • Trastuzumab treatment was independently associated with poorer PFS and OS for patients who used BB prior to initiating trastuzumab therapy for advanced HER2-positive breast cancer. • BB use potentially has a negative effect on patients with HER2-positive advanced breast cancer. • Future studies with larger sample sizes are needed to validate our findings.

Intraoperative hypotension in noncardiac surgery patients with chronic beta-blocker therapy: A matched cohort analysis.

STUDY OBJECTIVE: To explore the incidence of intraoperative hypotension in patients with chronic beta-blocker therapy, expressed as time spent, area and time-weighted average under predefined mean arterial pressure thresholds. DESIGN: Retrospective analysis of a prospective observational cohort registry. SETTING: Patients ≥60 years undergoing intermediate- to high-risk noncardiac surgery with routine postoperative troponin measurements on the first three days after surgery. PATIENTS: 1468 matched sets of patients (1:1 ratio with replacement) with and without chronic beta-blocker treatment. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was the exposure to intraoperative hypotension in beta-blocker users vs. non-users. Time spent, area and time-weighted average under predefined mean arterial pressure thresholds (55-75 mmHg) were calculated to express the duration and severity of exposure. Secondary outcomes included incidence of postoperative myocardial injury and thirty-day mortality, myocardial infarction (MI) and stroke. Furthermore, analyses for patient subgroup and beta-blocker subtype were conducted. MAIN RESULTS: In patients with chronic beta-blocker therapy, no increased exposure to intraoperative hypotension was observed for all characteristics and thresholds calculated (all P > .05). Beta-blocker users had lower heart rate before, during and after surgery (70 vs. 74, 61 vs. 65 and 68 vs. 74 bpm, all P < .001, respectively). Postoperative myocardial injury (13.6% vs. 11.6%, P = .269) and thirty-day mortality (2.5% vs. 1.4%, P = .055), MI (1.4% vs. 1.5%, P = .944) and stroke (1.0% vs 0.7%, P =  .474) rates were comparable. The results were consistent in subtype and subgroup analyses. CONCLUSIONS: In this matched cohort analysis, chronic beta-blocker therapy was not associated with increased exposure to intraoperative hypotension in patients undergoing intermediate- to high-risk noncardiac surgery. Furthermore, differences in patient subgroups and postoperative adverse cardiovascular events as a function of treatment regimen could not be demonstrated.