BB Use Research Articles

Pharmacogenomic Effects of β-Blocker Use on Femoral Neck Bone Mineral Density.

ContextRecent studies have shown that β-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to nonusers, likely due to the suppression of adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects.ObjectiveTo investigate potential single-nucleotide variations (SNVs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy x-ray absorptiometry, and genetic data from the Framingham Heart Study’s (FHS) Offspring Cohort. We then sought to validate our top 4 genetic findings using data from the Rotterdam Study, the BPROOF Study, the Malta Osteoporosis Fracture Study (MOFS), and the Hertfordshire Cohort Study.MethodsWe used sex-stratified linear mixed models to determine SNVs that had a significant interaction effect with BB use on femoral neck (FN) BMD across 11 gene regions. We also evaluated the association of our top SNVs from the FHS with microRNA (miRNA) expression in blood and identified potential miRNA-mediated mechanisms by which these SNVs may affect FN BMD.ResultsOne variation (rs11124190 in HDAC4) was validated in females using data from the Rotterdam Study, while another (rs12414657 in ADRB1) was validated in females using data from the MOFS. We performed an exploratory meta-analysis of all 5 studies for these variations, which further validated our findings.ConclusionThis analysis provides a starting point for investigating the pharmacogenomic effects of BB use on BMD measures.

β-Blocker use is not associated with improved clinical outcomes in women with breast cancer: a meta-analysis.

Background: Evidence remains inconsistent regarding the potential influence of β-blocker (BB) use on clinical outcomes in women with breast cancer. We aimed to evaluate the association between BB and prognosis of breast cancer in an updated meta-analysis.Methods: Follow-up studies comparing the clinical outcomes of breast cancer in women with and without use of BB were included by search of PubMed, Embase, and Cochrane’s Library. A random-effect model was used to pool the results.Results: Seventeen observational studies were included. Pooled results did not support a significant association between BB use and breast cancer recurrence (risk ratio [RR] = 0.85, 95% confidence interval [CI]: 0.68–1.07, P=0.17), breast cancer related deaths (RR = 0.83, 95% CI: 0.65–1.06, P=0.14), or all-cause deaths (RR = 1.01, 95% CI: 0.91–1.11, P=0.91) in women with breast cancer. Study characteristics such as sample size, definition of BB use, follow-up durations, adjustment of menopausal status, or quality score did not significantly affect the results. Subgroup analyses showed that BB may be associated with a trend of reduced risk of all-cause deaths in women with breast cancer in prospective studies (two datasets, RR = 0.81, P=0.05), but not in retrospective studies (eight datasets, RR = 1.06, P=0.16; P for subgroup analyses = 0.02).Conclusions: Current evidence from observational studies does not support a significant association between BB use and improved prognosis in women with breast cancer.

397: Fetal growth patterns in women with maternal arrhythmias treated with beta blockers

We sought to evaluate the association between fetal growth and BB use in patients with stable maternal arrhythmias. This was a retrospective cohort analysis (IRB#15-405) comparing 35 singleton pregnancies complicated by maternal arrhythmias treated with BBs between 2006 and 2019 to 35 matched singleton pregnancies not affected by arrhythmia or BB use. Controls were matched by maternal age +/- 3 years, gestational age (GA) at delivery +/- 10 days, and race. Patients with structurally abnormal hearts, chronic hypertension, preeclampsia prior to 34 weeks GA, diabetes, and autoimmune disorders were excluded. Our outcomes of interest were estimated fetal weight (EFW) percentile values by third trimester ultrasound and BW percentiles. Variables were compared using Student's T-test. We found that the mean growth of the entire cohort was normal, with normal EFW and BW percentiles (57.74% +/- 27.42 and 51.23% +/- 30.82 with BB use and 47.42% +/- 21.60 and 56.94% +/- 23.20 in the control group respectively). The percentage of FGR infants were 5.7% (N=2) and 0.0% in the BB and control groups respectively, which is not statistically different from the general population. Both cases of FGR were associated with metoprolol use. There was no difference in burden of adverse events as defined by NICU stay, neonatal demise/stillbirth, placental abruption, or chorioamnionitis between groups. In this cohort of women with maternal arrhythmia treated with BBs, there was no significant difference in fetal growth patterns from the control group. This suggests that BB use may not be an independent risk factor for FGR as many indications for their use are confounding. These findings should be further explored in a larger cohort.

Association of Angiotensin-Converting Enzyme Inhibitors with Increased Mortality Among Patients with Isolated Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is associated with one-third of all deaths from trauma. Preinjury exposure to cardiovascular drugs may affect TBI outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) exacerbate brain cell damage and worsen functional outcomes in the laboratory setting. β-blockers (BBs), however, appear to be associated with reduced mortality among patients with isolated TBI. Examine the association between preinjury ACEI and BB use and clinical outcome among patients with isolated TBI. A retrospective cohort study of patients age ≥40years admitted to an academic level 1 trauma center with isolated TBI between January 2010 and December 2014 was performed. Isolated TBI was defined as a head Abbreviated Injury Scale (AIS) score ≥ 3, with chest, abdomen, and extremity AIS scores ≤ 2. Preinjury medication use was determined through chart review. All patients with concurrent BB use were initially excluded. In-hospital mortality was the primary measured outcome. Over the 5-year study period, 600 patients were identified with isolated TBI who were naive to BB use. There was significantly higher mortality (P = .04) among patients who received ACEI before injury (10 of 96; 10%) than among those who did not (25 of 504; 5%). A multivariate stepwise logistic regression analysis revealed a threefold increased risk of mortality in the ACEI cohort (P < .001), which was even greater than the twofold increased risk of mortality associated with an Injury Severity Score ≥ 16. A second analysis that included patients who received preinjury BBs (n = 98) demonstrated slightly reduced mortality in the ACEI cohort with only a twofold increased risk in multivariate analysis (P = .05). Preinjury exposure to ACEIs is associated with an increase in mortality among patients with isolated TBI. This effect is ameliorated in patients who receive BBs, which provides evidence that this class of medications may provide a protective benefit.

12-LB: Beta Blocker Type and Hypoglycemia in Hospitalized Patients

Background: Although β-blockers (BB) could increase the risk of hypoglycemia, the difference between subtypes on hypoglycemia and mortality have not been studied. Aim: To determine the relationship between type of BB and incidence of hypoglycemia and mortality in hospitalized patients. Methods: We retrospectively identified non-critically ill hospitalized patients who were undergoing bedside glucose monitoring over a 2 year period. Admission BB was categorized as carvedilol (C) or selective BB (SBB). Other nonselective BB were excluded. Hypoglycemia was defined as any glucose &amp;lt; 70 mg/dl within 24 hours of admission (Hypo24) or throughout hospitalization (HypoT) and any glucose &amp;lt;40 mg/dl throughout hospitalization (Hypo40). Results: There were 1022 patients on C, 886 on SBB, and 10,217 on no BB. After controlling for other variables, the odds of Hypo24 HypoT and Hypo40 were higher for BB recipients, and the odds were greater for SBB vs. carvedilol for HypoT (Table). Findings were not observed in heart failure patients. Hypo24, HypoT, and Hypo40 were all associated with increased mortality in adjusted models among non-BB and C recipients, but not among SBB recipients. Conclusions: BB use is associated with hypoglycemia, except in heart failure. C is associated with lower odds of hypoglycemia compared to SSB. Moreover, hypoglycemia associated mortality was attenuated with C. The findings warrant further study among patients with diabetes. Disclosure C. Long: None. P.F. Binkley: None. K.M. Dungan: Advisory Panel; Self; Eli Lilly and Company, Elsevier, Sanofi-Aventis. Research Support; Self; Eli Lilly and Company, GlaxoSmithKline plc., Novo Nordisk Inc., Sanofi-Aventis, Viacyte. Other Relationship; Self; DKBmed, UpToDate.

Hypertension as a predictor of advanced colorectal cancer outcome and cetuximab treatment response.

Adrenergic receptor stimulation is involved in the development of hypertension (htn) and has been implicated in cancer progression and dissemination of metastases in various tumours, including colon cancer. Adrenergic antagonists such as beta-blockers (bbs) demonstrate inhibition of invasion and migration in colon cancer cell lines and have been associated with decreased mortality in colorectal cancer (crc). We examined the association of baseline htn and bb use with overall (os) and progression-free survival (pfs) in patients with pretreated, chemotherapy refractory, metastatic crc (mcrc). We also examined baseline htn as a predictor of cetuximab efficacy. Using data from the Canadian Cancer Trials Group co.17 study [cetuximab vs. best supportive care (bsc)], we coded baseline htn and use of anti-htn medications, including bbs, for 572 patients. The chi-square test was used to assess the associations between those variables and baseline characteristics. Cox regression models were used for univariate and multivariate analyses of os and pfs by htn diagnosis and bb use. Baseline htn, bb use, and anti-htn medication use were not found to be prognostic for improved os. Baseline htn and bb use were not significant predictors of cetuximab benefit. In chemorefractory mcrc, neither baseline htn nor bb use is a significant prognostic factor. Baseline htn and bb use are not predictive of cetuximab benefit. Further investigation to determine whether baseline htn or bb use have a similarly insignificant impact on prognosis in patients receiving earlier lines of treatment remains warranted.

Impact of Concomitant Use of Beta blocker, Statin, Aspirin, and Metformin on Central Hemodynamics and Arterial Stiffness in Hypertension

Objective: To assess the impact of concomitant use of aspirin, BB (metoprolol), statin (atorvastatin), and metformin on central haemodynamics and arterial stiffness parameters in treated hypertensive patients. Materials and Methods: We did a cross-sectional study on 476 treated hypertensives. Oscillometric PWA was accomplished by Mobil-o-Graph (IEM, Germany) and groups were stratified using low-dose aspirin, statin, BB, or metformin. Parameters studied were brachial hemodynamics (BP, heart rate, and rate pressure product), arterial stiffness (augmentation pressure, augmentation index, pulse wave velocity, total arterial stiffness, and pulse pressure amplification), and central hemodynamics (central BP, cardiac output, and stroke work). Results: All pairs were matched by or comparable for major confounding factors except concomitant use of drugs. The use of BB, aspirin, and statin had favorable effect on brachial and central hemodynamics. Metformin use had effect more on central than brachial hemodynamics. BB and metformin had negative, statin had indifferent, and aspirin had positive effect on arterial stiffness. Only few of these differences had statistical significance. Frequency of central pulse pressure ≥40 was insignificantly affected by drugs studied. Conclusions: Concomitant aspirin, BB, and metformin in hypertensives have favorable effects on hemodynamics, brachial more than central. Arterial stiffness has positive impact of metformin and negative impact of BB use. These effects must be considered in studies focusing hypertensive therapies. It remains inconclusive whether these results are due to drugs or their indication.

BoneBridge implantation in patients with single-sided deafness resulting from vestibular schwannoma resection: objective and subjective benefit evaluations

Background: The BoneBridge could rehabilitate hearing for patients with single-sided deafness (SSD).Objectives: To evaluate the objective and subjective benefits of BoneBridge implantation in patients after vestibular Schwannoma resection and to explore the factors affecting the benefits.Material and methods: We prospectively enrolled all 15 patients implanted with BoneBridge after VS resection from January to June 2017. The primary outcome was the ability to hear in noisy conditions. The secondary outcomes were the soft-band BoneBridge try-on rate, the frequency of BB use, the sound source localization test result, and questionnaire measures of quality of life (QoL).Results: Patients showed better speech recognition ability in the presence of noise with the BoneBridge. The BoneBridge provided no help in sound localization, although most patients reported subjective sound localization benefits. The results of QoL questionnaires showed significant satisfaction with BoneBridge implantation. The unilateral hearing deprivation duration and high education levels had significant impacts on the subjective benefits of patients.Conclusions: The BoneBridge could improve speech recognition performance in complex auditory backgrounds, as well as QoL, especially in patients with short unilateral hearing deprivation durations and high education levels.Significance: The BoneBridge is an effective hearing aid for single-sided deafness patients after VS removal.

Urinary proteomic signatures associated with β-blockade and heart rate in heart transplant recipients

ObjectivesHeart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on β-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature.MethodsIn 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins.ResultsIn adjusted analyses, HF1, HF2 and CKD273 (p ≤ 0.024) were higher in BB users than non-users with a similar trend for ACSP75 (p = 0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (p ≥ 0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (p ≤ 0.014). There were no differences in the urinary biomarkers (p ≥ 0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments.ConclusionsBB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial.

Validity of Performance and Outcome Measures for Heart Failure.

Background Numerous quality metrics for heart failure (HF) care now exist based on process and outcome. What remains unclear, however, is if the correct quality metrics are being emphasized. To determine the validity of certain measures, we compared correlations between measures and reliability over time. Measures assessed include guideline-recommended β-blocker (BB), any BB, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker, mineralocorticoid receptor antagonist, and hydralazine/isosorbide dinitrate (in blacks) use among candidates, 30-day mortality, 1-year mortality, and 30-day readmission. Methods and Results This was an observational cohort analysis using chart review and electronic resources for 55 735 patients from 102 Veterans Affairs medical centers hospitalized with HF from 2008 to 2013. Assessments of convergent validity and reliability were performed. Significant correlations were found between in-hospital rates of ACE inhibitor use and the following measures: BB use, 30-day mortality, and 1-year mortality. Guideline-recommended BB use was also significantly correlated with mineralocorticoid receptor antagonists, 30-day mortality, and 1-year mortality. There was no correlation between 30-day readmission rates and any therapy or mortality. Measure reliability over time was seen for guideline-recommended BBs ( r=0.57), mineralocorticoid receptor antagonists ( r=0.50), 30-day mortality ( r=0.29), and 1-year mortality ( r=0.31). ACE inhibitor and readmission rates were not reliable measures over time. Conclusions BB use, ACE inhibitor use, mortality, and mineralocorticoid receptor antagonist use are valid measures of HF quality. Thirty-day readmission rate did not seem to be a valid measure of HF quality of care. If the goal is to identify high-quality HF care, the emphasis on decreasing readmission rates might be better directed towards improving usage of the recommended therapies.

Beta-Blocker Usage and Hypoglycemia in Hospitalized Patients with Diabetes Mellitus

Background: Although ?-blockers (BB) theoretically increase the risk of severe or prolonged hypoglycemia, studies have suggested that BB may decrease the risk of hypoglycemia-associated arrhythmias and death. However, there is little evidence in hospitalized patients on insulin. Aim: To determine the relationship between BB use and incidence of hypoglycemia and mortality in hospitalized patients. Methods: We retrospectively identified non-critically ill hospitalized patients receiving subcutaneous insulin and undergoing bedside glucose monitoring over a 2 year period. BB and basal insulin use were identified on the admission medication list. Hypoglycemia, defined as any glucose &amp;lt; 70 mg/dl within 24 hours of admission (Hypo24) or throughout the hospitalization (HypoT) and any glucose &amp;lt;40 mg/dl throughout the hospitalization (Hypo40) were compared between patients with and without BB. Results: 13,424 patients were included, with 2648 patients receiving a BB at admission (19.7%). After controlling for other variables, the odds of Hypo24 HypoT and Hypo40 were higher for BB recipients (Hypo24 OR 3.79, 95% CI 3.21-4.50, p&amp;lt;0.0001, fully adjusted model; HypoT OR 7.70, 95% CI 6.77-8.77, p&amp;lt;0.0001, fully adjusted model; Hypo40 OR 1.95, 95% CI 1.49-2.57, p&amp;lt;0.0001). However, there was a significant interaction across basal insulin usage, with increased odds of HypoT and Hypo40 among basal insulin non-users but not basal insulin users. Hypo24, HypoT, and Hypo40 were associated with increased mortality in adjusted models. There was evidence of an interaction by BB status in the relationship between Hypo24 and mortality (with increased mortality among non-users but not users), but not at other time points. Conclusions: BB use is associated with higher risk of hypoglycemia in hospitalized basal insulin non-users, but not basal insulin users. Hypoglycemia is associated with increased hospital mortality, regardless of BB use, but early hypoglycemia-associated mortality risk is attenuated by BB use. Disclosure J. Merrill: None. K.M. Dungan: Research Support; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi-Aventis. Research Support; Self; Sanofi-Aventis, GlaxoSmithKline plc.. Consultant; Self; GlaxoSmithKline plc.. Research Support; Self; AstraZeneca. Other Relationship; Self; DKBmed, Horizon, Projects in knowledge, Rockpointe.

URINARY PROTEOMIC SIGNATURES ASSOCIATED WITH BETA-BLOCKADE AND HEART RATE IN HEART TRANSPLANT RECIPIENTS

Objective: Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on β-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature. Design and method: In 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins. Results: In adjusted analyses, HF1, HF2 and CKD273 (p < = 0.024) were higher in BB users than non-users with a similar trend for ACSP75 (p = 0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (p > = 0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (p < = 0.014). There were no differences in the urinary biomarkers (p > = 0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments. Conclusions: BB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial.

Abstract 208: A Large, Retrospective Cohort Study Comparing Cardiovascular Outcomes With β-blocker Combination Treatment in Patients With Hypertension

Objectives: Hypertension is a major risk factor for cardiovascular (CV) events. While β-blockers (BBs) lower blood pressure and reduce CV event risk, the comparative CV event risk and rate of hospitalization due to CV events between hypertensive patients treated with vasodilatory β 1 -selective antagonist/β 3 agonist, nebivolol (NEB), and non-vasodilatory β 1 -selective BBs, atenolol (ATN) and metoprolol (MET), is unknown. Methods: Incident users of NEB, ATN or MET receiving ≥1 additional antihypertensive were identified from US claims data (2007-2014). First BB claim on/after 1/1/2008 defined index drug and date. Follow-up lasted ≥6 months, until index drug cessation or other BB use. Treatment cohorts (N=16,787 each) were matched by the number of antihypertensive drug classes used in follow-up and on propensity score (1:1) to balance confounders (follow-up duration, baseline demographics and clinical characteristics). Clinical outcomes based on matched cohorts were: hospitalization risk for composite CV outcome (myocardial infarction [MI], congestive heart failure, stroke, and angina; assessed by Cox proportional hazards regression) and event rate ratio for CV-related hospitalizations (assessed by count regression with negative binomial distribution) comparing ATN and MET with NEB. Both regressions were adjusted for concomitant antihypertension medication possession ratios (≥75%) and baseline confounders balanced in matching. Results: Compared with NEB, hospitalization risk due to composite CV events, MI, and angina was significantly higher with ATN and MET (Table). The unadjusted rate of all hospitalizations due to composite CV events per 1,000 persons per year was significantly greater in ATN and MET users compared with NEB users, while the adjusted ratio of composite CV event rate was significantly greater with MET, but not ATN (Table). Conclusions: In adults receiving combination antihypertension therapy, NEB treatment was associated with a lower risk for CV-related hospitalization than either ATN or MET. Lower risk of hospitalization was supported by event rate data, as patients receiving NEB combined with other antihypertensives were hospitalized less frequently than patients receiving combination therapy with either ATN or MET.

Effects of β-Blockers on Maximal Heart Rate Prediction Equations in a Cardiac Population.

To derive specific maximal heart rate (HRmax) prediction equations for a coronary artery disease (CAD) population based upon status of β-blocker (BB) therapy and to compare these to prior HRmax equations (Fox and Brawner-specific for CAD). We retrospectively reviewed stress echocardiogram treadmill tests in patients with CAD, dividing subjects into 3 groups based upon BB use on test day: not prescribed BB therapy (no BB group; n = 110); held for 12 to 24 hr prior (held BB group; n = 155); and continued taking (took BB group; n = 72). Derived HRmax equations for our CAD population were no BB = 200 - 0.79 × age; held BB = 193 - 0.71 × age; and took BB = 168 - 0.51 × age. Achieved HRmax mean was not significantly different between held BB and no BB groups; however, HRmax in the took BB group was significantly lower. Fox and Brawner (no BB)-HRmax equations significantly overestimated (+6 and +9 mean bias) and underestimated (-8 and -6 mean bias) achieved HRmax in no BB and held BB groups, respectively. The Brawner (no BB) equation intercept and slope were not significantly different from our CAD-held BB and no BB equations. The Brawner (on BB) equation intercept and slope were similar to our took BB equation, but greatly underestimated achieved HRmax (-17 mean bias). For patients holding BB therapy on test day, a similar CAD HRmax estimation equation to those patients never on BB can be used, comparable to the Brawner (no BB) equation. Further research is needed to determine when patients should take their BB therapy in conjunction with exercise testing.

Association of Hypertension and &amp;lt;i&amp;gt;β&amp;lt;/i&amp;gt;-Blocker Use with Depression during Pregnancy

Objective: To evaluate the association between hypertension and β-blocker (BB) use and antepartum depression risk. Patients and Methods: We conducted a retrospective cohort study of women who delivered within our integrated health system between 2009 and 2015, and completed an Edinburgh Postnatal Depression Scale (EPDS) during pregnancy. Increased depression risk was defined as EPDS score ≥ 10, or an affirmative answer to question ten, endorsing self-harm. Antepartum hypertension was determined by blood pressure measurements and provider ICD-9 codes. Regression analyses examined the independent associations of BB use and hypertension on antepartum depression risk. Results: Of 9192 deliveries during the study time frame, 5% were hypertensive. Within the hypertensive group, 103 (22%) used a single agent BB (BB Group), 325 (68%) required no antihypertensive medication (No-Med Group), and 48 (10%) used a non-BB single agent or multi-agent therapy (All-Other Group). After adjusting for covariates, compared to normotensive pregnancies, antepartum hypertension was significantly associated with both EPDS score ≥ 10 (adjusted odds ratio [aOR] 1.61, 95% confidence interval [CI] 1.17 - 2.21) and endorsement of self-harm (aOR 1.76, 95% CI 1.05 - 2.95). In further analyses of depression risk in hypertensive pregnancies, there was no difference between the BB Group and No-Med Group (EPDS score ≥ 10, aOR 1.22, 95% CI 0.56 - 2.63; self-harm, aOR 0.84, 95% CI 0.32 - 2.21), or between the All-Other Group and No-Med Group (EPDS ≥ 10, aOR 1.42, 95% CI 0.57 - 3.54; self-harm, aOR 1.04, 95% CI 0.29 - 3.74). Conclusion: Women with antepartum hypertension have increased risk for depression and thoughts of self-harm. β-Blocker use is not associated with further increased risk.

Beta blockers and improved progression-free survival in patients with advanced HER2 negative breast cancer: a retrospective analysis of the ROSE/TRIO-012 study

Recent retrospective studies suggest that beta-adrenergic blocking drugs (BB) are associated with improved outcomes in patients with a range of cancers. Although limited and discordant data suggest that BB may increase overall survival (OS) in localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC. To explore the association between BB use and BC outcomes, we retrospectively reviewed ROSE/TRIO-012, a double-blinded, multinational phase III trial that randomized 1144 patients with HER2-negative advanced BC to first-line docetaxel in combination with ramucirumab or placebo. We compared progression-free survival (PFS), OS, overall response rate, and clinical benefit rate in patients who received BB to those who did not. 153/1144 (13%) patients received BB; 62% prior to enrolment and 38% began after enrolment. Median PFS in BB treated patients was longer than in patients who did not receive them (10.3 versus 8.3 months; HR 0.81; 95% CI 0.66-0.99; P = 0.038). Patients treated with BB only after enrolment had even higher median PFS (15.5 versus 8.3 months, P < 0.001). In the TNBC subset, median PFS was 13.0 months with BB, compared to 5.2 months without BB (HR 0.52; 95% CI 0.34-0.79; P = 0.002). The benefit of BB intake in PFS was independent of treatment-emergent hypertension (P = 0.476) but associated with treatment arm (P = 0.037). The test for interactions between BB and treatment arm was not significant (P = 0.276). No differences were seen in OS, overall response rate, or clinical benefit rate. A validation dataset analysis had consistent but less substantial improved outcomes for women with node positive operable breast cancer receiving BB in the BCIRG-005 trial. In this exploratory analysis, BB intake was associated with significant improvement in PFS, particularly in patients with TNBC and patients not previously exposed to BB. NCT00703326.

Daily propranolol administration reduces persistent injury-associated anemia after severe trauma and chronic stress.

After severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow (BM) erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators, such as ferroportin, transferrin, and transferrin receptor-1 (TFR-1), is unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a nonselective β blocker, restores BM function and improves iron homeostasis. Male Sprague-Dawley rats were subjected to LCHS ± BB and LCHS/CS ± BB. BB was achieved with propranolol (10 mg/kg) daily until the day of sacrifice. Hemoglobin, plasma EPO, plasma hepcidin, BM cellularity and BM erythroid colony growth were assessed. RNA was isolated to measure transferrin, TFR-1 and ferroportin expression. Data are presented as mean ± SD; *p < 0.05 versus untreated counterpart by t test. The addition of CS to LCHS leads to persistent anemia on posttrauma day 7, while the addition of BB improved hemoglobin levels (LCHS/CS: 10.6 ± 0.8 vs. LCHS/CS + BB: 13.9 ± 0.4* g/dL). Daily BB use after LCHS/CS improved BM cellularity, colony-forming units granulocyte, erythrocyte, monocyte megakaryocyte, burst-forming unit erythroid and colony-forming unit erythroid cell colony growth. LCHS/CS + BB significantly reduced plasma EPO levels and increased plasma hepcidin levels on day 7. The addition of CS to LCHS resulted in decreased liver ferroportin expression as well as decreased BM transferrin and TFR-1 expression, thus, blocking iron supply to erythroid cells. However, daily BB after LCHS/CS improved expression of all iron regulators. Daily propranolol administration after LCHS/CS restored BM function and improved anemia after severe trauma. In addition, iron regulators are significantly reduced after LCHS/CS, which may contribute to iron restriction after injury. However, daily propranolol administration after LCHS/CS improved iron homeostasis.

Very Low Proportion of Patients have Previous Non-Ischaemic Cardiomyopathy as Sole Indication for Ongoing ACEi and BB Use

Very Low Proportion of Patients have Previous Non-Ischaemic Cardiomyopathy as Sole Indication for Ongoing ACEi and BB Use

Status of β-blocker use and heart rate control in Chinese patients with stable coronary artery disease

To observe the current status of β-blocker (BB) use and heart rate control in Chinese patients with stable coronary artery disease (SCAD) based on subgroup data of the prospective observational longitudinal registry of patients with stable coronary artery disease (CLARIFY). The CLARIFY study is an international prospective observational registry of outpatients with SCAD. From November 2009 to July 2010, patients with SCAD were enrolled, and demographic information, clinical indicators, medication and blood flow reconstruction were collected. Patients were divided in three mutually exclusive categories by baseline pulse palpation heart rate(HR)≤60 beats per minute (bpm)(n=397), 61-69 bpm(n=782), and ≥70 bpm(n=1 443). The patients were also divided into taking BB or not taking BB groups. The aim of present study is to describe and analyze the current status and factors related to the HR control and BB use in the Chinese subgroup of CLARIFY. A total of 2 622 patients were enrolled from 56 centers across China. The mean age was (63.6±10.3) years old with 75.6% (1 983) male patients, 55.0% (1 443) patients had HR≥70 bpm. Mean HR measure by electrocardiogram(ECG) was (69.4±10.2)bpm, 50.9% (1 334 cases) patients had myocardial infarction(MI) history. A total of 21.9%(575 cases) patients had anginal symptoms; coronary angiography was performed in 88.8%(2 327 cases) of the patients. 76.2%(1 997 cases) patients were treated with BB (any molecule and any dose), 2.7% (70 cases) with digoxin or derivatives, 3.9% (103 cases) with verapamil or diltiazem, and 1.8% (47 cases) with amiodarone or dronedarone and 0.1%(2 cases) received ivabradine. BB use was similar among 3 HR groups(P>0.05). The independent risk factors associated with HR≥70 bpm were diabetes(OR=1.31), current smoker(OR=1.57), chronic heart failure(CHF) with NYHA Ⅲ (OR=2.13) and increased diastolic blood pressure (OR=1.30). Conversely, high physical activity (OR=0.61), former smoker (OR=0.76) and history of percutaneous coronary intervention(PCI, OR=0.80) were associated with lower risk of HR≥70 bpm (all P<0.05). The independent risk factors associated with non-BB use were older age (OR=1.11, 95%CI 1.01-1.47, P=0.005), lower diastolic blood pressure (OR=1.47, 95%CI 1.32-1.68, P=0.012), no history of MI (OR=1.86, 95%CI 1.43-2.44, P<0.001) or PCI (OR=1.94, 95%CI 1.55-3.73, P<0.001), asthma/chronic obstructive pulmonary disease (OR=1.32, 95%CI 1.15-1.99, P<0.001). A total of 76.2% Chinese SCAD patients received BB medication but more than half of them did not reach the optimal HR. Clinical characteristics including diabetes, current smoker, CHF, increased diastolic blood pressure and no PCI were associated with poorly controlled HR(≥70 bpm). More efforts including adjusting the type and dose of heart rate lowering drugs are needed to achieve optimal HR control in Chinese SCAD patients. Clinical Trail Registry International Standard Randomized Controlled Trial, ISRCTN43070564.

Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis: A Propensity-Matched Cohort Study

Atrial fibrillation (AF) during sepsis is associated with increased morbidity and mortality, but practice patterns and outcomes associated with rate- and rhythm-targeted treatments for AF during sepsis are unclear. This was a retrospective cohort study using enhanced billing data from approximately 20%of United States hospitals. We identified factors associated with IV AF treatments (?-blockers [BBs], calcium channel blockers [CCBs], digoxin, or amiodarone) during sepsis. We used propensity score matching and instrumental variable approaches to compare mortality between AF treatments. Among 39,693 patients with AF during sepsis, mean age was 77 ± 11 years, 49%were women, and 76%were white. CCBs were the most commonly selected initial AF treatment during sepsis (14,202 patients [36%]), followed by BBs (11,290 [28%]), digoxin (7,937 [20%]), and amiodarone (6,264 [16%]). Initial AF treatment selection differed according to geographic location, hospital teaching status, and physician specialty. In propensity-matched analyses, BBs were associated with lower hospital mortality when compared with CCBs (n= 18,720; relative risk [RR], 0.92; 95%CI, 0.86-0.97), digoxin (n=13,994; RR, 0.79; 95%CI, 0.75-0.85), and amiodarone (n= 5,378; RR, 0.64; 95%CI, 0.61-0.69). Instrumental variable analysis showed similar results (adjusted RR fifth quintile vsfirst quintile of hospital BB use rate, 0.67; 95%CI, 0.58-0.79). Results were similar among subgroups with new-onset or preexisting AF, heart failure, vasopressor-dependent shock, or hypertension. Although CCBs were the most frequently used IV medications for AF during sepsis, BBs were associated with superior clinical outcomes in all subgroups analyzed. Our findings provide rationale for clinical trials comparing the effectiveness of AF rate- and rhythm-targeted treatments during sepsis.