Association Of Beta-blocker Use Research Articles

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

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. 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±5.5years, 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 36months. 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. 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.

ASSOCIATION OF BETA BLOCKER USE AND COPD MORTALITY: A SYSTEMATIC REVIEW

Background: Chronic obstructive pulmonary disease (COPD) it is currently the third greatest cause of mortality worldwide and one of the main causes of morbidity Aims: This systematic review is to review the association of beta blocker use and COPD mortality. Methods: This study demonstrated compliance with all requirements by means of a comparison with the standards established by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020. Thus, the specialists were able to guarantee that the research was as current as feasible. Publications released between 2014 and 2024 were considered for this search strategy. This was accomplished by utilizing a number of distinct online reference sites, including Pubmed, ScienceDirect, and SagePub. It was determined that reviews, previously published works, and partially completed works would not be included. Result: In the PubMed database, the results of our search brought up 249 articles, whereas the results of our search on SCIENCE DIRECT brought up 18.876 articles, our search on SAGEPUB brought up 4.844 articles. The results of the search conducted for the last year of 2014 yielded a total 131 articles for PubMed, 6.875 articles for SCIENCE DIRECT and 1.840 articles for SAGEPUB. In the end, we compiled a total of 8 papers, 5 of which came from PubMed, 2 of which came from SCIENCE DIRECT and 1 of which came from SAGEPUB. We included eight research that met the criteria. Conclusion: In summary, beta blockers showed the effect to reduce the exacerbation or exacerbation related mortality of COPD in some cases. More studies needed in the future for more evidence of the use of beta blockers as the treatments in patients with COPD.

Association of Beta-Blocker Use With Exercise Capacity in Participants With Heart Failure With Preserved Ejection Fraction: A Post Hoc Analysis of the RELAX Trial

Patients with heart failure with preserved ejection fraction (HFpEF) often receive β-blocker (BB) therapy for management of co-morbidities. However, the association of BB therapy with exercise capacity and health-related quality of life (HRQL) in HFpEF is not well-studied. In this post hoc analysis of the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF (RELAX) trial, which included patients with chronic stable HFpEF with peak exercise capacity assessment at baseline and at 12 and 24 weeks of follow-up, we evaluated the association of BB use with the measures of exercise capacity (peak exercise oxygen uptake), anaerobic threshold, and HRQL (Minnesota living with heart failure questionnaire). Separate linear mixed-effect models were constructed for each outcome with adjustment for treatment arm, demographics, medical history, left ventricular ejection fraction, and duration of heart failure. Of the 216 study participants (median age 69 years, 48.2% women), 76% reported BB use at baseline. Participants with (vs without) BB therapy were older (70 vs 63.5 years, p = 0.001) and had a higher prevalence of ischemic heart disease (44% vs 23%, p = 0.01). In the adjusted linear mixed model, BB use over time was not associated with peak exercise oxygen uptake (β 95% confidence interval [CI] 0.2 (-0.31 to 0.7), p = 0.5) and 6-minute walk distance (β 95% CI 14.69 [-14.25 to 43.63], p = 0.3). However, BB use was associated with a higher anaerobic threshold (β 95% CI 0.32 (0.02 to 0.62), p = 0.036) and better HRQL (lower quality of life as assessed by Minnesota living with heart failure questionnaire score) (β 95% CI -6.68 [-10.96 to -2.4], p = 0.002). Future trials are needed to better evaluate the effects of BB on exercise capacity in patients with chronic stable HFpEF.

The Association of Beta-Blocker Use and Bone Mineral Density Level in Hemodialysis Patients: A Cross-Sectional Study.

Background and Objectives: Osteoporosis results in increasing morbidity and mortality in hemodialysis patients. The medication for treatment has been limited. There is evidence that beta-blockers could increase bone mineral density (BMD) and reduce the risk of fracture in non-dialysis patients, however, a study in hemodialysis patients has not been conducted. This study aims to determine the association between beta-blocker use and bone mineral density level in hemodialysis patients. Materials and Methods: We conducted a cross-sectional study in hemodialysis patients at Thammasat University Hospital from January 2018 to December 2020. A patient receiving a beta-blocker ≥ 20 weeks was defined as a beta-blocker user. The association between beta-blocker use and BMD levels was determined by univariate and multivariate linear regression analysis. Results: Of the 128 patients receiving hemodialysis, 71 were beta-blocker users and 57 were non-beta-blocker users (control group). The incidence of osteoporosis in hemodialysis patients was 50%. There was no significant difference in the median BMD between the control and the beta-blocker groups of the lumbar spine (0.93 vs. 0.91, p = 0.88), femoral neck (0.59 vs. 0.57, p = 0.21), total hip (0.73 vs. 0.70, p = 0.38), and 1/3 radius (0.68 vs. 0.64, p = 0.40). The univariate and multivariate linear regression analyses showed that the beta-blocker used was not associated with BMD. In the subgroup analysis, the beta-1 selective blocker used was associated with lower BMD of the femoral neck but not within the total spine, total hip, and 1/3 radius. The multivariate logistic regression showed that the factors of age ≥ 65 years (aOR 3.31 (1.25−8.80), p = 0.02), female sex (aOR 4.13 (1.68−10.14), p = 0.002), lower BMI (aOR 0.89 (0.81−0.98), p = 0.02), and ALP > 120 U/L (aOR 3.88 (1.33−11.32), p = 0.01) were independently associated with osteoporosis in hemodialysis patients. Conclusions: In hemodialysis patients, beta-blocker use was not associated with BMD levels, however a beta-1 selective blocker used was associated with lower BMD in the femoral neck.

Association of beta blocker use with new-onset heart failure and mortality in atrial fibrillation without pre-existing heart failure: the Fushimi AF registry

Abstract Background Heart failure (HF) is one of the major complications in atrial fibrillation (AF). We previously reported that not a few AF patients without pre-existing HF (defined as prior HF hospitalization, New York Heart Association functional class≥2, or left ventricular ejection fraction (LVEF)&amp;lt;40%) subsequently developed new-onset HF. Beta blockers are the established therapy for HF, but it remains unclear whether beta blockers prevent new-onset HF and improve outcomes in AF patients without preexisting HF. Methods In the Fushimi AF registry, 778 of 3,262 patients without pre-existing HF were receiving beta blockers at baseline. We investigated the incidence of new-onset HF defined as cardiac death or HF hospitalization, and all-cause death in a propensity-matched cohort (N=1,198; mean age, 71 years; 39% female; mean LVEF, 66%). Additionally, annual follow-up prescription data before the onset of events were collected in 294 of patients with beta blockers and 395 of those without beta blockers. We also investigated the association of starting or stopping beta blockers with the incidence of new-onset HF and all-cause death. Results During the median follow-up of 5.8 years, new-onset HF and all-cause death occurred in 77 (12.9%) and 118 (19.7%) of patients with beta blockers, and 70 (11.7%) and 131 (21.9%) of those without beta blockers, respectively. Incidence of new-onset HF was comparable between patients with and without beta blockers (Figure 1), and incidence of all-cause death was also comparable between the two groups (Figure 2). In exploratory subgroup analyses, there was no interaction in the association of beta blockers with the incidence of events, except for pulse rate for new-onset HF and left atrial size for all-cause death. Hazard ratio of beta blockers for new-onset HF tended to be lower in patients with higher pulse rates (&amp;gt;84 bpm) (Figure 1), and that for all-cause death was lower in those without left atrial enlargement (Figure 2). Of patients with follow-up prescription data, beta blockers were stopped in 55 (18.7%) and started in 97 (24.6%) patients, respectively. Patients with starting beta blockers had higher pulse rate (78.5±17.3 vs 74.9±13.9 bpm; p=0.03) and more symptomatic AF (58.8% vs 46.0%; p=0.03) compared to those without starting beta blockers, while there was no difference in baseline characteristics between those with and without stopping beta blockers. During the follow-up, the incidences of new-onset HF and all-cause death were also comparable between the patients with and without stopping beta blockers and those with and without starting beta blockers. Conclusion Beta blockers were not associated with the incidence of new-onset HF and all-cause death in AF patients without pre-existing HF. However, the exploratory subgroup analyses suggested the existence of subjects who may benefit from beta blockers. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi Sankyo, Novartis Pharma, MSD, Sanofi-Aventis, and Takeda Pharmaceutical.

Association of beta blocker use and hearing ability in adults: a cross-sectional study

Objectives To investigate the potential association between beta blocker use and hearing ability in adults and to discern whether this effect is dose-dependent. Design Cross-sectional analyses. Multiple linear regression was performed with hearing ability as the dependent variable and beta blocker use as the independent variable. The independent variable was classified into three dose categories for secondary analysis. Adjustments were made for age, gender, educational level, and tobacco smoking status. Study sample 1636 adults, 75 of whom reported being on beta blockers, from the internet-based Netherlands Longitudinal Study on Hearing (NL-SH). Results No significant association was found between beta blocker use and hearing ability in noise. In the adjusted regressions, beta blocker use changed the speech reception threshold in noise (SRT) by −0.04 dB signal-to-noise ratio (SNR) (95%CI [−0.67 to 0.58], p = 0.890). Medium dose beta blocker use changed SRT by −0.42 dB SNR (95%CI [−1.38 to 0.71], p = 0.433), while a high dose changed it by −0.26 dB SNR (95%CI [−1.74 to 1.4], p = 0.767). Conclusions No evidence was found for beta blocker-induced changes in hearing ability. Future studies on this topic should favour case-control and cohort study designs, while focussing on a hypertensive population to minimise confounding by indication.

Beta-blockers are associated with incident heart failure: a secondary analysis of the systolic blood pressure intervention (SPRINT) trial

Abstract Background The Systolic Blood Pressure Intervention Trial (SPRINT) evaluated whether a blood pressure (BP) goal of less than 120mmHg versus less than 140mmHg would reduce cardiovascular outcomes in subjects with at least one cardiovascular risk factor and without heart failure. Participating investigators were encouraged to use any antihypertensive medication class with a strong evidence base. The SPRINT trial was halted early due to a lower rate of the composite primary outcome in the 120mmHg group, which was mainly driven by a reduction in heart failure (HF). Objective As there is a concern that beta-blocker use may be associated with an excess risk for incident HF in subjects with a normal left ventricular systolic function, we evaluated the association between beta-blocker use and HF. Beta-blockers were compared with other major classes of antihypertensive medications. We also studied the association of antihypertensive class with loop-diuretic initiation. Methods and results In the 9,012 subjects, without HF at baseline, the association of beta-blocker exposure and incident HF was examined using time-variant competing risk analysis. Beta-blocker exposure was associated with an increased HF risk (HR 1.18; CI 1.07–1.30; p&amp;lt;0.001) and more frequent and earlier loop diuretic-use compared to other antihypertensive agents (both p&amp;lt;0.01). Sensitivity analyses of propensity-score matched cohorts confirmed a strong association of beta-blocker use and HF. Other major antihypertensive medication classes did not show this association. Conclusions Beta-blocker exposure was associated with a higher incidence of HF in hypertensive subjects without HF at baseline. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health

MiRNA Mechanisms Underlying the Association of Beta Blocker Use and Bone Mineral Density.

Osteoporosis is a debilitating and costly disease that causes fractures in 33% of women and 20% of men over the age of 50 years. Recent studies have shown that beta blocker (BB) users have higher bone mineral density (BMD) and decreased risk of fracture compared with non-users. The mechanism underlying this association is thought to be due to suppression of adrenergic signaling in osteoblasts, which leads to increased BMD in rodent models; however, the mechanism in humans is unknown. Also, several miRNAs are associated with adrenergic signaling and BMD in separate studies. To investigate potential miRNA mechanisms, we performed a cross-sectional analysis using clinical data, dual-energy X-ray absorptiometry (DXA) scans, and miRNA and mRNA profiling of whole blood from the Framingham Study's Offspring Cohort. We found nine miRNAs associated with BB use and increased BMD. In parallel network analyses, we discovered a subnetwork associated with BMD and BB use containing two of these nine miRNAs, miR-19a-3p and miR-186-5p. To strengthen this finding, we showed that these two miRNAs had significantly higher expression in individuals without incident fracture compared with those with fracture in an external data set. We also noted a similar trend in association between these miRNA and Z-score as calculated from heel ultrasound measures in two external cohorts (SOS-Hip and SHIP-TREND). Because miR-19a directly targets the ADRB1 mRNA transcript, we propose BB use may downregulate ADRB1 expression in osteoblasts through increased miR-19a-3p expression. We used enrichment analysis of miRNA targets to find potential indirect effects through insulin and parathyroid hormone signaling. This analysis provides a starting point for delineating the role of miRNA on the association between BB use and BMD. © 2020 American Society for Bone and Mineral Research (ASBMR).

Multivariable analysis of association of beta-blocker use and survival in advanced ovarian cancer

ObjectiveIn this study, we sought to evaluate the relationship between survival and beta blocker use in both the primary and interval debulking setting while adjusting for frequently co-administered medications. MethodsWe performed a retrospective cohort study reviewing charts of women who underwent primary or interval cytoreduction for stage IIIC and IV epithelial ovarian cancer. The exposure of interest was beta-blocker use identified at the time of cytoreduction. The outcomes of interest were PFS and OS. We collected demographic/prognostic variables and information about use of aspirin, metformin, and statins. We used the Kaplan-Meier method and Cox proportional hazards models in survival analyses. Results534 women who underwent surgery for stage IIIC or IV ovarian cancer were included in the study. The median age at diagnosis was 64 and 84.8% of women had serous carcinoma. We identified 105 women (19.7%) on a beta-blocker of whom 94 (90%) were on a cardioselective beta-blocker. Additionally, 24 women (4.5%) were on metformin, 91 (17%) on aspirin, and 128 (24%) on a statin. In univariable analysis, beta-blocker users had a median overall survival of 29 months vs 35 months among non-users (hazard ratio HR = 1.52, p = 0.007). After adjustment for important demographic, clinical, and histopathologic factors, as well as use of other common medications, beta-blocker use remain associated with an increased hazard of death (adjusted HR 1.57, p = 0.006). ConclusionIn this retrospective study, we found that patients identified as being on a beta-blocker at the time of surgery had worse overall survival and greater risk of death when compared to those patients not on betablockers. Importantly, 90% of patients on beta-blockers were identified as being on a cardioselective beta-blocker.

The Association of Beta-Blocker Use to Cognitive Impairment among Adults with Hypertension or Cardiovascular Diseases in the United States.

Some studies have shown that beta-blocker use is associated with better cognitive impairment. However, these studies did not control for pain. The relationship between pain and cognitive impairment has been exhaustively investigated. The association of beta blockers to cognitive impairment in the presence of chronic pain is still unknown. To examine the independent association of beta-blocker use to cognitive impairment among adults with hypertension or Cardiovascular Diseases (CVDs). We used a cross-sectional study design. We derived data on 8,279 adults from the 2015 Medical Expenditure Panel Survey (MEPS). Study participants were adults (age > 21 years), with hypertension or CVDs and without intracranial injury, Parkinson, Alzheimer's disease and Related Dementia. Cognitive impairment was measured based on 1) confusion or memory loss; 2) problems making decisions, or 3) supervision for participant's safety. Anti-hypertensive medications were categorized into 1) beta-blockers; 2) other anti-hypertensives; and 3) no antihypertensive medication. We used multivariable survey logistic regressions to examine the association between beta-blockers and cognitive impairment after controlling for biological factors, pain, chronic conditions, socioeconomic status, access to healthcare services, behavioral, socio-cultural and external environmental factors. Overall, 24.2%, 41.9%, and 33.9% reported using beta-blockers, other antihypertensives, and no antihypertensive medications, respectively; 18.1% participants reported cognitive impairment. After controlling for pain, beta-blocker use was not significantly associated with cognitive impairment (AOR= 1.22, 95%CI= 1.00-1.49). In fully adjusted models, the AOR for beta-blockers use was 1.05 (95%CI = 0.84-1.31). In this first large cross-sectional study, we found that the use of beta-blockers was not associated with cognitive impairment. Future prospective studies that include pain management and blood pressure control are needed to confirm the findings.

P1666Do beta-blockers increase the risk for hospitalizations in heart failure with preserved ejection fraction? A secondary analysis of beta-blocker use in the TOPCAT trial

Abstract Background The use of beta-blockers for treatment of heart failure (HF) with a reduced ejection fraction (EF) is unequivocally beneficial, but their role in the treatment of preserved EF (HFpEF) remains unclear. Purpose In a contemporary HFpEF cohort, we sought to assess the association of HF hospitalizations and the use of beta-blockers in patients with an EF above and below 50%. Methods The TOPCAT trial tested spironolactone vs. placebo among patients with HFpEF, including some with mild reductions in EF between 45–50%. The primary outcome was a composite of cardiovascular (CV) mortality, aborted cardiac arrest, or HF hospitalizations. Medication use, including beta-blockers, was reported at each visit and hospitalization. In the 1,761 participants from the Americas, we compared the association of beta-blocker use (vs. no use) and HF hospitalization or CV mortality using Cox proportional hazards models adjusted for baseline demographics, history of myocardial infarction, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and hypertension. The analyses were repeated in the EF strata ≥50% and &lt;50%. Results Among patients included in the current analysis (mean age 72 years, 50% female, 78% white), 1,496/1,761 (85%) received beta-blockers and 1,566/1,761 (89%) had an EF ≥50%. HF hospitalizations and CV mortality occurred in 399/1,761 (23%) and 223/1,761 (13%) of participants, respectively. Beta-blocker use was associated with an increase in risk of HF hospitalization among patients with preserved EF ≥50% [HR 1.56, (95% CI 1.09–2.24), p=0.01] and was associated with a reduction in risk of hospitalization in patients with an EF &lt;50% [HR 0.42, (95% CI 0.18- 0.99), p&lt;0.05]. We found a significant interaction for EF threshold and beta-blocker use on incident HF hospitalizations (p=0.01). There were no differences in CV mortality. Figure 1. Kaplan Meier incidence plots Conclusions Beta-blocker use was associated with an increase in HF hospitalizations in patients with HFpEF (EF≥50%) but did not affect CV mortality. Further research is needed to confirm these findings and elucidate causality.

The association of beta-blocker use with mortality in elderly patients with congestive heart failure and advanced chronic kidney disease.

Whether the survival benefit of β-blockers in congestive heart failure (CHF) from randomized trials extends to patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 but not receiving dialysis] is uncertain. This was a retrospective cohort study using administrative datasets. Older adults from Ontario, Canada, with incident CHF (median age 79 years) from April 2002 to March 2014 were included. We matched new users of β-blockers to nonusers on age, sex, eGFR categories (>60, 30-60, <30), CHF diagnosis date and a high-dimensional propensity score. Using Cox proportional hazards models, we examined the association of β-blocker use versus nonuse with all-cause mortality. We matched 5862 incident β-blocker users (eGFR >60, n = 3136; eGFR 30-60, n = 2368; eGFR <30, n = 358). There were 2361 mortality events during follow-up. β-Blocker use was associated with reduced all-cause mortality [adjusted hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.54-0.64]. This result was consistent across all eGFR categories (>60: adjusted HR 0.55, 95% CI 0.49-0.62; 30-60: adjusted HR 0.63, 95% CI 0.55-0.71; <30: adjusted HR 0.55, 95% CI 0.41-0.73; interaction term, P = 0.30). The results were consistent in an intention-to-treat analysis and with β-blocker use treated as a time-varying exposure. β-Blocker use is associated with reduced all-cause mortality in elderly patients with CHF and CKD, including those with an eGFR <30. Randomized trials that examine β-blockers in patients with CHF and advanced CKD are needed.

Clinical outcomes with beta-blockers in stable patients undergoing percutaneous coronary intervention with adequate left ventricular ejection function

Objective: To investigate the impact of beta-blockers on long-term outcomes in patients who underwent percutaneous coronary intervention (PCI) for stable coronary artery disease (SCAD) with adequate left ventricular ejection function (LVEF). Methods: A total of 3 946 consecutive SCAD patiens who underwent PCI with adequate LVEF between January and December 2013 in Fuwai Hospital were prospectively included in this study. According to beta-blocker use at discharge, patients were divided into no-beta-blocker group (n=309) and beta-blocker group (n=3 637). Major adverse cardiovascular and cerebrovascular events (MACCE) including all-cause death, myocardial infarction, revascularization, stroke and stent thrombosis at 2 years were compared between the two groups. Multivariate Cox regression analysis and Propensity-score matched analysis were used to identify independent risk factors of poor prognosis. Results: Compared with those in the beta-blocker group, patients of no-beta-blocker group were more likely to have lower body mass index, less complex comorbidities, slower heart rate either on admission or at discharge. There was no significant association of beta-blocker use with 2-year mortality (0.8% versus 1.3%, hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.23 to 1.86, P=0.421), myocardial infarction ( HR 0.66, 95% CI 0.24 to 2.64, P=0.718) or MACCE (HR 0.70, 95% CI 0.65 to 1.32, P=0.674). Results were similar in propensity score-matched analysis. Conclusions: In this large, prospective, single-center study, patients with beta-blocker prescription appear to have more risk factors. No beta-blockers at discharge is not an independent risk factor of poor prognosis at up to 2 years among stable patients who underwent PCI with adequate LVEF.

Multivariable analysis of association of beta-blocker use and survival in advanced ovarian cancer

Multivariable analysis of association of beta-blocker use and survival in advanced ovarian cancer

Stage‐specific associations between beta blocker use and prognosis after colorectal cancer

Recent observational studies have suggested that the use of beta blockers might be associated with better prognosis after cancer. Because evidence is limited for colorectal cancer (CRC), the association of beta blocker use and prognosis was investigated in a large population-based cohort of patients with CRC. Between 2003 and 2007, information on beta blocker use at diagnosis and potential confounders was collected by personal interviews for 1975 patients with CRC. Vital status, cause of death, and recurrence status were assessed during a median follow-up time of 5.0 years. The associations of beta blocker use and overall, CRC-specific, and recurrence-free survival were estimated by Cox proportional hazard regression. In addition, beta blocker subgroup, site, and stage-specific analyses were performed. After adjustment for covariates including sociodemographic, cancer-related, and lifestyle factors and comorbidity and medications, no significant association between beta blocker use at diagnosis and prognosis was observed for all stages combined. However, in stage-specific analyses, beta blocker use was associated with longer overall survival (hazard ratio = 0.50; 95% confidence interval = 0.33-0.78) and CRC-specific survival (hazard ratio = 0.47; 95% confidence interval = 0.30-0.75) in stage IV patients. For these patients, median overall survival was 18 months longer and CRC-specific survival was 17 months longer for beta blocker users than for nonusers (38 versus 20 months and 37 versus 20 months, respectively). These results suggest that beta blocker use might be associated with longer survival in patients with stage IV CRC.

Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy

BackgroundPreclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. Patients and methodsWe retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). ResultsIn univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P < 0.01), DFS (P < 0.01), and OS (P = 0.01), but not LRPFS (P = 0.33) compared with patients not taking beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). ConclusionBeta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes.

Association of Beta-Blocker Use and Selectivity With Outcomes in Patients With Heart Failure and Chronic Obstructive Pulmonary Disease (from OPTIMIZE-HF)

In patients with heart failure (HF) with chronic obstructive pulmonary disease (COPD), concerns exist regarding β blockers, particularly noncardioselective β blockers, precipitating bronchospasm or attenuating the benefit of inhaled β(2) agonists. The aim of this study was to test the hypothesis that noncardioselective β blockers would not be associated with worse outcomes compared with cardioselective β blockers in patients with concomitant COPD in a large HF registry. A retrospective analysis of patients from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) who had systolic dysfunction, documentation of β-blocker status, and follow-up information available after index hospitalization (n= 2,670) was performed. The associations between cardioselective and noncardioselective β blockers and the end points of 60- to 90-day mortality and mortality or rehospitalization in patients with (n= 722) and without (n=1,948) COPD were analyzed using regression modeling. The models were adjusted for covariate predictors of β-blocker use at discharge and clinical predictors of outcomes. Noncardioselective and cardioselective β blockers were associated with lower risk-adjusted mortality in patients with and without COPD. There was no evidence that β-blocker selectivity was associated with a difference in outcomes between patients with and those without COPD (p for interaction >0.10 for both outcomes). In conclusion, despite concerns regarding β blockers in patients with HF with COPD, there was no evidence that β-blocker selectivity was associated with differences in outcomes for patients with HF with COPD versus those without.

Beta blocker use and colorectal cancer risk

Recently, it has been postulated that long-term use of beta blockers might decrease the risk of certain types of cancer because of weakening of norepinephrine signaling. Previous studies on colorectal cancer (CRC) yielded inconsistent results, but lacked information on covariates. Thus, the authors investigated the association of beta blocker use and CRC risk in a large population-based case-control study (DACHS study). Between 2003 and 2007, information on beta blocker use and potential confounders was collected by personal interviews for 1762 CRC cases and 1708 control individuals from Germany. The association of CRC risk and beta blocker use and subclasses of beta blockers was estimated by multiple logistic regression. In addition, site- and stage-specific analyses were performed. After adjustment for covariates, no association was observed with beta blocker use (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.86-1.29) or with duration of beta blocker use. Also, the analysis by subclasses of beta blockers (cardioselectivity) and active ingredients (metoprolol, bisoprolol, carvedilol, and atenolol) or by CRC subsite showed no associations. In stage-specific analyses, long-term beta blocker use (6+ years) was associated with a significantly higher risk of stage IV CRC (OR, 2.02; 95% CI, 1.25-3.27). Our adjusted results do not support the hypothesis that beta blocker use is associated with decreased risk of CRC. In contrast, we found a positive association of long-term beta blocker use and risk of stage IV CRC. The latter result should be further evaluated in future studies.

Antihypertensive Treatment With ACE Inhibitors or -Blockers and Risk of Incident Atrial Fibrillation in a General Hypertensive Population

Secondary analyses of clinical trial data suggest that, compared with other agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are associated with lower risk of incident atrial fibrillation (AF) in patients with heart failure, but data from the hypertension trials have been inconsistent. Information is scant about the association of beta-blocker use with AF risk in hypertensive patients without heart failure. We conducted a population-based case-control study to determine whether antihypertensive treatment with ACE inhibitors/ARBs or beta-blockers, compared with diuretics, was associated with the risk of incident AF in a community practice setting. All patients (810 AF cases, 1,512 control subjects) were members of Group Health (GH), an integrated health-care delivery system, were pharmacologically treated for hypertension, and did not have heart failure. Medical records were reviewed to confirm the diagnosis of incident AF and to collect information on medical conditions and health behaviors. Information on antihypertensive medications was obtained from a pharmacy database. Single-drug users of an ACE inhibitor/ARB had a lower risk of incident AF compared with single-drug users of a diuretic (adjusted odds ratio 0.63, 95% confidence interval 0.44-0.91). Single-drug use of beta-blockers was not significantly associated with lower AF risk (odds ratio 1.05, 95% confidence interval 0.73-1.52), and also none of the most commonly used two-drug regimens was significantly associated with AF risk, in comparison with single-drug use of diuretic. In a general hypertensive population without heart failure, single-drug use of ACE inhibitors/ARBs was associated with lower AF risk.

Association of beta-blocker use with increased aortic wave reflection

Studies have found less cardiovascular risk reduction in patients treated with beta-blockers (BBs) compared with other agents. We compared the severity of aortic atherosclerosis, arterial stiffness, and wave reflection in patients treated and not treated with BBs. Seventy-two patients, 37 treated with BBs and 35 not treated, referred for transesophageal echocardiography were studied. Augmentation index (AI), heart-rate-corrected AI (AI-75), aortic systolic (SBP) and diastolic blood pressure, pulse wave velocity (PWV), and aortic intima-media thickness (MAIMT) were measured. There were no differences in MAIMT (2.8 ± 1.6 mm vs. 2.4 ± 1.2 mm, P = .20) and PWV (8.9 ± 2.0 m/s vs. 8.5 ± 2.6 m/s, P = .46) between the BB and non-BB groups. The BB group had higher AI (28.7 ±11.9% vs. 22.3 ± 14.1%, P = .04), AI-75 (27.7 ± 10.7% vs. 20.1± 11.0%, P = .005), aortic SBP (140 ± 21 mm Hg vs. 125 ± 21 mm Hg, P = .01), and aortic pulse pressure (62 ± 20 mm Hg vs. 47 ± 19 mm Hg, P = .01) than the non-BB group despite similar brachial blood pressure. BB use was associated with increased aortic wave reflection despite similar degree of aortic atherosclerosis.