Benefit Of Beta-blockers Research Articles

Association between use of beta-blockers and mortality/morbidity in patients with heart failure with reduced, midrange or preserved ejection fraction and advanced chronic kidney disease

Abstract Background Beta-blockers reduce mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, patients with advanced chronic kidney disease (CKD) were underrepresented in landmark trials. Purpose We evaluated if beta-blockers are associated with improved survival and cardiovascular outcomes in patients with HFrEF and advanced CKD, and if potential benefits of beta-blockers would extend also to HFpEF and HFmrEF with advanced CKD. Methods We identified 3906 persons with an ejection fraction <40% and advanced CKD (eGFR <30 mL/min/1.73m2) enrolled in the Swedish Heart Failure Registry during 2001–2016. We did not exclude patients with atrial fibrillation. The associations between beta-blocker use, 5-year all-cause mortality, and the composite of time to cardiovascular (CV) mortality/first HF hospitalization were assessed by multivariable Cox regression. Analyses were adjusted for 36 variables, including demographics, laboratory measures, comorbidities, medication use, medical procedures, and socioeconomic status. To assess consistency, the same analyses were performed in a positive control cohort of 12,673 patients with moderate CKD (eGFR <60–30 mL/min/1.73m2). Analyses were repeated in individuals with HF with preserved ejection fraction (HFpEF; EF ≥50%) or midrange ejection fraction (HFmrEF; EF 40–49%). Results In HFrEF and advanced CKD, 89% received beta-blockers. Overall, median (IQR) age was 81 (74–86) years, 36% were women and median eGFR was 26 (20–28) ml/min/1.73m2. During a median of 1.3 years follow-up, 2086 (53.4%) individuals had a subsequent HF hospitalization, and 2954 (75.6%) individuals died, of which 2089 (70.1%) due to cardiovascular causes. Beta-blocker use was associated with a significant reduction in 5-year all-cause mortality [adjusted hazard ratio (HR) 0.86; 95% confidence interval (CI) 0.76–0.96)] and CV mortality/HF hospitalization (HR 0.87; 95% CI 0.77–0.98). The magnitude of the associations between beta-blocker use and outcomes was similar to that observed for HFrEF patients with mild/moderate CKD [all-cause mortality: 0.85 (95% CI 0.78–0.91); CV mortality/HF hospitalization: 0.88 (95% CI 0.82–0.96)]. Adjusted HRs were 0.88 (95% CI 0.77–1.02) and 1.07 (95% CI 0.92–1.24) for individuals with HFpEF and advanced CKD and 0.95 (95% CI 0.80–1.13) and 1.13 (95% CI 0.94–1.36) for individuals with HFmrEF and advanced CKD, for all-cause mortality and CV mortality/HF hospitalization, respectively. Conclusion Despite lack of trial evidence, the use of beta-blockers in patients with HFrEF and advanced CKD was high in routine Swedish care, and was independently associated with reduced mortality to the same degree as HFrEF with moderate CKD. However, these benefits were not observed in patients with HFpEF or HFmrEF with severe CKD. Funding Acknowledgement Type of funding source: None

Premorbid, cardioselective beta-blocker exposure decreases ICU mortality in septic patients defined by sepsis-3

Abstract Introduction Beta-blockers may exert a protective effect against the catecholaminergic myocardial injury in septic patients. The difference between cardioselective and non-selective beta blockers was not fully elaborated. The aim of this study was to investigate the association between premorbid prescriptions of different class of beta-blockers and mortality rate in septic patients. Methods We retrospectively screened 2678 patients admitted to the ICU during December 2015 to July 2017. Premorbid beta-blocker exposure was defined as prescription of any beta blocker for at least 1 month. Bisoprolol, esmolol, and atenolol were classified as cardioselective beta-blockers, and others were classified as non-selective beta-blockers. Results Among 1262 septic patients, 209 (16.6%) cases were long-term beta-blockers users. Patients with premorbid beta-blocker exposure were associated with higher BP, lower HR, lactate concentration, and improved ICU mortality. However, only premorbid cardioselective beta-blocker users (adjusted HR 0.26; 95% CI 0.11–0.64; p=0.003), but not non-selective beta-blocker users (adjusted HR 0.66; 95% CI 0.29–1.51; p=0.326), were associated with reduced ICU mortality. Conclusion Only premorbid cardioselective beta-blockers, but not non-selective beta-blockers, were associated with improved mortality in septic patients. These findings supported the cardioprotective effect and clinical benefits of beta-blocker in septic patients. Kaplan-Meier Curve of ICU Mortality Funding Acknowledgement Type of funding source: None

Long-term prognostic benefit of beta-blockers use after discharge in patients with Tako-Tsubo syndrome

Abstract Background Tako-tsubo Syndrome (TS) seems to be associated with a catecholamine-mediated mechanism. However, the impact of beta-blockers (BB) in-hospital and after discharge still remain uncertain. Objectives: The purpose of the study was to examine whether BB use after discharge in patients with TS, was associated with lower long-term mortality and recurrence. Methods Using a national multicentre large-scale inpatient database (RETAKO Registry), we analysed patients with a definitive TS diagnosis. Results A total of 970 patients were analysed (568 with BB therapy and 402 no-BB therapy). After discharge and over a median of follow-up of 1.1 years, treatment with BB have no shown prognostic effectiveness in terms of mortality and TS recurrence in unadjusted and adjusted Cox analysis (HR 0.86; 95% CI: 0.59 to 1.27; and 0.95; 95% CI: 0.57–1.13, respectively). Conclusions This data suggests that use of beta-blockers after hospital discharge has not shown long-term prognostic benefit in patients with Tako-tsubo Syndrome. Prognostic impact of BB in TS. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Retako webpage was funded by a non-conditioned Astrazeneca scholarship.

Heart Rate Reduction Following Beta- Blocker Up-Titration is Associated With Patients with Heart Failure with Reduced Ejection Fraction

Introduction Lower resting heart rate (HR) is associated with favorable outcomes in patients with heart failure with reduced ejection fraction (HFrEF, ≤40%). Clinical trials supported the benefits of beta-blockers in HFrEF patients have implied that targeting a lower resting HR ( Hypothesis Greater reduction in resting HR with beta-blocker uptitration is associated with improved outcomes in patients with HFrEF. Methods We identified HFrEF patients with at-least 3 follow-up visits for purpose of beta-blocker up-titration, with serially documented resting HR that defined “hypo-responder” or “hyper-responder” if their changes were in the lowest or highest quartile, respectively. Primary outcome was composite of all-cause mortality or heart failure (HF) hospitalization. Results In our cohort of 997 patients (median age 62.7 [IQR 53, 73] years), 246 were hyper-responders (median HR decrease of 22 [IQR 17, 31] bpm, 77% achieved target HR Conclusions Greater reduction in resting HR following beta-blocker up-titration was associated with decreased risk of all-cause mortality and HF hospitalization.

Meta-analysis of the benefit of beta-blockers for the reduction of isolated atrial fibrillation incidence after cardiac surgery.

ObjectivesPostoperative atrial fibrillation (POAF) is a common problem of cardiac surgery. Beta-blockers are recognized as effective prophylactic agents available for POAF management. To better understand its effect on isolated atrial fibrillation after cardiac surgery, a meta-analysis was conducted.MethodsRandomized controlled trials (RCTs) were searched and filtered by comparing the efficacy of beta-blockers and control users in isolated POAF for cardiac surgery. Seventeen RCTs were identified and analyzed by typical meta-analysis methods. The search was performed from inception to May 31, 2020. Subgroup analyses were conducted for type of surgery and beta-blocker, starting time and route of administration of beta-blocker, and dosage of intravenous landiolol hydrochloride.ResultsBeta-blockers were effective in reducing isolated POAF risk (risk ratio [RR], 0.52 [0.41, 0.66], P = .31, I2 = 12%). In subgroup analyses, beta-blocker administration during postoperative period (RR, 0.43 [0.29, 0.62], P = .84, I2 = 0%) and on-pump coronary artery bypass graft (RR, 0.34 [0.04, 3.15], P = .56, I2 = 0%) had lowest risk of isolated POAF incidence. Intravenous landiolol hydrochloride at 2 μg/kg/min also had low risk of isolated POAF occurrence.ConclusionsBeta-blocker treatment helps to reduce isolated atrial fibrillation incidence after cardiac surgery. Our subgroup analyses also reveal postoperative beta-blocker administration after on-pump coronary artery bypass graft surgery is most effective in reducing isolated POAF risk. Intravenous landiolol hydrochloride at a dosage of 2 μg/kg/min has also displayed favorable results. Further trials may be required to explore these factors.

Response to beta-blockers and natriuretic peptide level in acute heart failure: analysis of data from the Korean acute heart failure registry.

To investigate the effect of beta-blockers according to NP levels and HF phenotypes because natriuretic peptide (NP) level can be used to risk-stratify HF patients regardless of left ventricular ejection fraction (LVEF). Of 5,625 patients in the Korean acute heart failure registry, we included patients with LVEF and NP levels. HF phenotypes were defined as HF with reduced ejection fraction (HFrEF) (EF ≤ 40%), HF with midrange ejection fraction (HFmrEF) (40% < EF < 50%), and HF with preserved EF (HFpEF) (EF ≥ 50%). Patients were further stratified by NP tertiles. Primary outcome was 5-year all-cause mortality according to beta-blocker use at discharge. Both B-type NP (BNP) (r = -0.279, P < 0.001) and N-terminal pro-BNP (r = -0.186, P < 0.001) levels correlated inversely with LVEF. During a median follow-up duration of 961days, 1560 (35.3%) patients died. In HFrEF, patients taking beta-blockers showed better survival regardless of NP levels. Regarding HFmrEF, there was no mortality difference between those taking and not taking beta-blockers. In HFpEF, beta-blocker use demonstrated lower mortality in those in the 3rd NP tertile (log-rank P = 0.041) but not in those in the 1st and 2nd NP tertiles (log-rank P > 0.05). After adjusting covariates, the use of beta-blockers was associated with a 38%-reduced mortality (hazard ratio: 0.62; 95% confidence interval: 0.39-0.98; P = 0.040) in HFpEF patients in the 3rd NP tertile but not in those in 1st and 2nd tertiles. We confirm that the use of beta-blockers is beneficial in patients with HFrEF. Furthermore, we extend the benefits of beta-blockers to patients with HFpEF and high NP levels. ClinicalTrial.gov identifier: NCT01389843 URL: https://clinicaltrials.gov/ct2/show/NCT01389843.

Poor adherence to beta-blockers is associated with increased long-term mortality even beyond the first year after an acute coronary syndrome event

Background: Acute coronary syndrome (ACS) patients are widely treated with long-term beta-blocker therapy after cardiac event. Especially for low-risk patients, the benefits of beta-blockers on survival and the optimal therapy duration remain unclear. We investigated the effect of adherence to beta-blockers on long-term survival of ACS patients.Methods and results: A total of 1855 consecutive ACS patients who underwent angiography and survived 30 days after were followed for a median of 8.6 years. During follow-up, 30.1% (n = 558) of patients died. Adherence was assessed as yearly periods covered by medication purchases and investigated as a dynamic time-dependent variable in Cox proportional hazards models. In a univariable model, non-adherence to beta-blockers was associated with higher all-cause mortality (Hazard ratio [HR] 2.99, 95% confidence interval [CI] 2.50−3.57; p < .001). Results were similar in multivariable models on both overall survival (HR 1.84, 95% CI 1.51−2.24; p < .001) and on 1-year landmark survival (HR 1.74, 95% CI 1.41−2.14; p < .001). In subgroup analyses, the increase in all-cause mortality was consistent among low-risk patients (HR 1.60, 95% CI 1.16−2.21; p = .004).Conclusion: Poor adherence to beta-blockers is associated with increased long-term mortality among ACS patients. Even low-risk patients seem to benefit from long-term beta-blocker therapy.Key messagesAdherence to secondary prevention medications diminishes drastically over the years after an ACS event.Non-adherence to β-blockers is associated with increased long-term mortality of ACS patients, and the effect on survival extends beyond the first year after an ACS event.Our follow-up was exceptionally lengthy with median follow-up period of 8.6 years.

Abstract P5-14-24: Interim analysis of the SAFE trial (NCT2236806): A randomized phase 3 study evaluating a cardiovascular disease prevention strategy using beta-blockers and/or ACE inhibitors in non-metastatic breast cancer patients treated with anthracyclines

Abstract Background. Several studies demonstrated the prophylactic benefit of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors for anthracyclines-based chemotherapy-induced cardiotoxicity. However, there is no consensus on management strategies at the time being. We present the interim analysis of the SAFE trial. Methods. The SAFE trial is a 2 × 2 factorial design randomized phase 3 study evaluating the impact of bisoprolol (B) (5 mg), ramipril (R) (5 mg), or both drugs as compared to placebo (P) on subclinical heart damage evaluated by speckle-tracking cardiac ultrasound. Enrolled patients included non-metastatic histology-proven breast cancer, treated with primary systemic therapy or adjuvant regimens based on anthracyclines with or without trastuzumab. Primary endpoint is evaluation of reduction in both systolic and diastolic, early and late subclinical cardiotoxicity measured with traditional echocardiography, pulsed tissue doppler, global linear strain (GLS), and 3-dimesional left ventricular ejection fraction (3D-LVEF). CT registry ID: NCT2236806; EudraCT number: 2015-000914-23. Results. A total of 191 out of 480 patients have been enrolled; overall 123 patients were available for the analysis (P=34; R=28; B=31; R+B=30). 3D-LVEF decreased at 3-month (-3.3%; p&amp;lt;0.001), at 6-month (-5.2%; p&amp;lt;0.001) and at 12-month (-3.7%; p=0.004) respect to T0 in P; at 3-month (-2.4%; p=0.001), at 6-month (-1.9%; p=0.010), at 12-month (-2.2%; p=0.045) in R. In B and R+B patients no significant changes were observed at 3- and 12-month, with a decrease at 6-month (-2.5% and 3.0%, respectively; p=0.002). Arm differences were significant (p=0.038). GLS increased at 3-mos (5.7%; p&amp;lt;0.001), at 6-mos (7.8%; p&amp;lt;0.001) and at 12-mos (7.1%; p&amp;lt;0.001) respect to T0 in P; at 3-month (2.7%; p=0.002), at 6-month (3.2%; p=0.014), but not at 12-month in R; no significant changes at 3-month, a significant increase at 6-month (2.7%; p=0.035), at 12-month (3.2%; p=0.008) in B; no significant changes at 3-, 6-, and 12-month in R+B. Arm differences were significant (p=0.002). Both R+B and the R arms showed a withdraw rate of 7%, with a dose reduction rates of 21% and 17%, respectively. Conclusion. At the interim analysis, a cardiovascular disease prevention strategy using beta-blockers and/or ACE inhibitors significantly impacted on subclinical heart damage. Citation Format: Lorenzo Livi, Icro Meattini, Francesca Martella, Calogero Saieva, Carlotta Becherini, Francesca Terziani, Isacco Desideri, Vieri Scotti, Carlotta Bacci, Mario Airoldi, Giacomo Allegrini, Domenico Amoroso, Luisa Fioretto, Giuseppe Barletta. Interim analysis of the SAFE trial (NCT2236806): A randomized phase 3 study evaluating a cardiovascular disease prevention strategy using beta-blockers and/or ACE inhibitors in non-metastatic breast cancer patients treated with anthracyclines [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-24.

Beta-Blockers for the Secondary Prevention of Myocardial Infarction in People with Dementia: A Systematic Review.

Background:Cardiovascular disease remains the most common cause of death in industrialized countries. The use of beta-blockers is well established as a secondary prevention of myocardial infarction. However, little is known about the benefits of beta-blockers for people living with dementia.Objective:To evaluate the use of beta-blockers in people with dementia who have had a myocardial infarction, in order to identify associations between medication use, mortality, re-infarction and functional decline.Methods:We searched for all studies (randomized trials, observational cohorts) reporting beta-blocker use in populations with both dementia and previous myocardial infarction. Relevant keywords were used in Medline, Embase, and Web of Science up to October 2018. Titles and abstracts were independently screened by two reviewers. Quality of eligible studies was assessed using the Newcastle-Ottawa Scale. PRISMA recommendations were followed throughout.Results:Two observational studies were included, representing 10,992 individuals in a community setting and 129,092 individuals from a hospital record-linkage study. One showed use of beta-blockers reduced all-cause mortality (HR 0.74 (95% CI 0.64– 0.86) alongside evidence for an increased rate of functional decline in individuals aged≥65 with moderate to severe cognitive impairment (OR 1.34 (95% CI 1.11– 1.61)). The second study did not find an association between beta-blocker use and mortality in the population living with dementia.Conclusion:There is insufficient evidence to support use of beta-blockers to persons living with dementia. A single study provides limited evidence that beta-blockers improve survival rates but with associated detrimental effects on functional status in nursing home residents with cognitive impairment. Decisions to continue beta-blockers in persons living with dementia should be made on an individual basis.

P3538Effect of beta-blockers on mortality in heart failure with mid-range and preserved ejection fraction: a meta-analysis

Abstract Background Despite the high mortality rate, there is no established therapy to improve survival in heart failure with mid-range ejection fraction (HFmrEF) or in heart failure with preserved ejection fraction (HFpEF). An individual patient-level analysis of major randomized controlled trials (RCTs) conducted by the Beta-Blockers in Heart Failure Collaborative Group (BB-HF) did not show clear mortality benefit of beta-blockers (BBs) in HFmrEF or HFpEF. However, due to the strict enrollment criteria, the patients who participated in these trials might represent a selected group of patients that is poorly representative of patients treated in routine clinical practice. In contrast, clinical characteristics of real-world patients are similar to those of patients enrolled in observational cohort studies (OCSs). Although many OCSs have examined the prognostic effect of BBs in HFmrEF/HFpEF, results are inconsistent due to limited power with small sample sizes and/or inadequate adjustment for known prognostic factors. Purpose We aimed to conduct a meta-analysis of OCSs and RCTs to determine the effect of BBs on mortality in HFmrEF/HFpEF. Methods A search of MEDLINE and EMBASE was conducted in November 2018. Clinical studies reporting the outcome of mortality for HF patients with EF≥0.40, being assigned to BB treatment and non-BB control group, were included. Results Seven OCSs with propensity score (PS) analysis (16,295 patients), 6OCSs without PS analysis (15,275 patients), and 4RCTs (1222 patients) were included for this meta-analysis. Forest plot of the effect of BBs on mortality is shown in Figure 1. Use of BBs was associated with reduced risk of mortality in the pooled analysis of OCSs with PS analysis (RR [95% CI] = 0.83 [0.74–0.92], P&lt;0.001) and in that of OCSs without PS analysis (0.70 [0.52–0.94], P&lt;0.05), but not in that of RCTs (0.88 [0.62–1.24], P=0.45). Overall, use of BBs was associated with reduced risk of mortality (RR [95% CI] = 0.82 [0.75–0.89], P&lt;0.001). No evidence of publication bias was found either in visual inspection of funnel plots or using the Egger test (P&gt;0.1). Figure 1 Conclusions Our meta-analysis showed that treatment with BBs for the HF patients with EF≥0.40 was associated with reduced risk of mortality. Our findings emphasize the importance of conducting new well-designed studies such as registry-based RCTs to confirm our observed potential survival benefit of BBs in HFmrEF or HFpEF.

Is preoperative chemoradiation in rectal cancer patients modulated by ACE inhibitors? Results from the Dutch Cancer Registry

Background and purposeThe aim of this study was to assess the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on tumor response to preoperative chemoradiation for rectal cancer. Materials and methodsData on patients who received chemoradiation prior to surgery for rectal cancer between 2010 and 2015 were retrieved from linkage between the PHARMO Database Network, Dutch Pathology Registry and Netherlands Cancer Registry. Pathological complete response rates (pCR) were compared between patients who did or did not use ACEIs/ARBs during treatment. Multivariable analysis was performed using logistic regression. ResultsOut of 345 patients, 92 patients (26.7%) used ACEIs/ARBs during treatment. Median age was 65 years (range 30–85). Older and male patients were more likely to use ACEIs/ARBs. pCR (ypT0N0) was observed in 17.4% of patients using ACEIs/ARBs compared to 14.6% of patients who did not use ACEIs/ARBs (p = 0.595). A good response (ypT0-1N0) was observed in 21.7% of ACEIs/ARBs patients vs. 19.4% of patients who did not use ACEIs/ARBs (p = 0.724). Multivariable analysis, taking into account background variables and co-medication, showed increased pCR in patients using beta-blockers (odds ratio 2.3, 95% confidence interval 1.0–5.4). ConclusionIn this retrospective cohort, the use of ACEIs/ARBs was not associated with tumor response to preoperative chemoradiation in rectal cancer patients. Thereby, the suggested potentiating effect of ACEIS/ARBs could not be confirmed in our study. Further research could be directed to investigate a possible benefit of beta-blockers or other anti-hypertensive drugs.

Beta-blocker target dosing and tolerability in a dedicated heart failure clinic in Johannesburg.

Despite the significant clinical benefits of beta-blockers in heart failure with reduced ejection fraction (HFrEF), prescription for and adherence to these agents is reported to be poor. There are few data on the use and tolerance of beta-blocker therapy in patients with HFrEF in South Africa and it is unknown whether these patients would benefit from further heart rate-lowering therapy. Data from all patients with HFrEF attending the heart failure clinic of Charlotte Maxeke Johannesburg Academic Hospital from January 2000 to December 2014 were retrospectively collected. We first determined the rates of beta-blocker intolerance in this population and then categorised the patients according to their most recent dose of beta-blocker (low, moderate or target dose) in order to identify factors associated with beta-blocker intolerance. Lastly, we used the data to identify patients who would be suitable for further treatment with heart rate-lowering therapy. Five hundred patients, with a median follow up of 58.7 months, were identified during the study period. Black South Africans constituted the majority (66.4%) and most patients had HFrEF due to hypertension (32.8%). At the last recorded clinic visit at the end of the study period, 489 patients (97.8%) were taking a beta-blocker with 59.8% prescribed a beta-blocker at target dose. Consistent with previous data, bradycardia was the commonest cause for failing to reach target beta-blocker dose. Only 61 (12%) patients were on no (n = 11) or low (n = 50) dose of beta-blocker at final clinic visit. As per current guidelines, only 10.6% (n = 53) of this cohort of patients would qualify for further treatment with heart rate-lowering therapy. In a dedicated heart failure clinic in South Africa, beta-blockers were well-tolerated in the treatment of HFrEF. The potential role of specific heart rate-lowering therapy in patients treated adequately with heart failure medication and proper up-titration of beta-blockers is relatively small.

A gradient of benefit of beta-blockers in acute coronary syndrome patients: from severely depressed ejection fraction up to the normal level.

A gradient of benefit of beta-blockers in acute coronary syndrome patients: from severely depressed ejection fraction up to the normal level.

Mechanisms of Improved Mortality Following Ablation: Does Ablation Restore Beta-Blocker Benefit in Atrial Fibrillation/Heart Failure?

Observational trials have shown that atrial fibrillation ablation favorably impacts long-term outcomes in systolic heart failure. These outcomes have been confirmed by randomized prospective trials highlighting the favorable impact of ablation on left ventricular function and remodeling, risk of heart failure hospitalization, and mortality. Ablation along with established heart failure medications is new and supported conceptually by the value of restoring sinus rhythm, avoiding long-term antiarrhythmic drugs, and minimizing drug-drug interactions. Observational data suggest a potential long-term benefit of beta-blockers with ablation that becomes augmented as follow-up is extended from 1to 5years.

Beta-blockers use from the general to the hemodialysis population

Beta-blockers have numerous indications in the general population and are strongly recommended in heart failure, post-myocardial infarction and arrhythmias. In hemodialysis patients, their use is based on weak evidence because of the lack of a sufficient number of randomized clinical trials. The strongest evidence is based on two trials. The first showed better survival with carvedilol in hemodialysis patients with four sessions per week and systolic heart failure. The second found reduced cardiovascular morbidity with atenolol compared to lisinopril in mostly black hypertensive hemodialysis patients. No clinical trials exist regarding myocardial infarction. Large retrospective studies have assessed the benefits of beta-blockers in hemodialysis. A large cohort of hemodialysis patients with new-onset heart failure showed better survival when treated with carvedilol, bisoprolol or metoprolol. Another recent one of 20,064 patients found out that metoprolol compared to carvedilol was associated with less all-cause mortality. There is still uncertainty also regarding the impact of dialysability of beta-blockers on patient's survival. On top of that, many observations suggested that beta-blockers were associated with a reduced rate of sudden cardiac death in hemodialysis patients but recent data show a link between bradycardia and sudden cardiac death questioning the benefit of beta-blockade in this population. Finally, what we know for sure so far is that beta-blockers should be avoided in patients with intradialytic hypotension associated with bradycardia.

Beta-blocker therapy reduces mortality in patients with coronary artery disease treated with percutaneous revascularization: a meta-analysis of adjusted results.

The long-term impact of beta blockers on prognosis in patients treated with contemporary therapies for coronary artery disease remains to be defined. All observational studies evaluating the impact of beta blockers in patients treated with coronary revascularization and contemporary therapies and adjusted with multivariate analysis were included. All-cause death was the primary endpoint, while Major Adverse Cardiac Events (MACE) (composite endpoint of all-cause death or myocardial infarction, MI) and MI were secondary endpoints. A total of 26 studies were included, with 863 335 patients. After 3 (1-4.3) years, long-term risk of all-cause death was lower in patients on beta blockers [odds ratio, OR 0.69 (0.66-0.72)], both for Acute Coronary Syndrome (ACS) [OR 0.60 (0.56-0.65)], and stable angina patients [OR 0.84 (0.78-0.91)], independently from ejection fraction [OR 0.64 (0.42-0.98) for reduced ejection fraction and OR 0.79 (0.69-0.91) for preserved ejection fraction]. The risk of long-term MACE was lower but NS for ACS patients treated with beta blockers [OR 0.83 (0.69-1.00)], as in stable angina. Similarly, risk of MI did not differ between patients treated with beta blockers or without beta blockers [OR 0.99 (0.89-1.09), all 95% confidence intervals]. Using meta-regression analysis, the benefit of beta blockers was increased for those with longer follow-up. The number needed to treat was 52 to avoid one event of all-cause death for ACS patients and 111 for stable patients. Even in percutaneous coronary intervention era, beta blockers reduce mortality in patients with coronary artery disease, confirming their protective effect, which was consistent for both ACS and stable patients indifferently of preserved or reduced ejection fraction.

Short-term effects of preoperative beta-blocker use for isolated coronary artery bypass grafting: A systematic review and meta-analysis

ObjectiveThe use of preoperative beta-blockers has been used as a quality standard for patients undergoing coronary artery bypass grafting (CABG). However, the benefits of beta-blockers use before CABG remain controversial. We performed a systematic review and meta-analysis to investigate the short-term effects of preoperative beta-blocker use for patients undergoing isolated CABG. MethodsWe searched PubMed, Embase, and the Cochrane Library for English articles published from inception to August 16, 2016. Observational studies comparing preoperative beta-blockers therapy or non-beta-blockers therapy were considered eligible for the current study. ResultsSix observational studies with 1,231,850 patients were included. The pooled analyses of unadjusted outcome (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71-0.95; P = .007) or risk-adjusted outcome (OR, 0.95; 95% CI, 0.92-0.97; P = .000) showed slight reduction in operative mortality, whereas an insignificant difference in mortality rate was observed in pooling postoperative data from propensity score analysis (OR, 0.97; 95% CI, 0.94-1.00; P = .088). Removing one study that used propensity-score covariate adjustment, subgroup analysis of propensity-matched patients (313,417 in each group) still generated a statistically nonsignificant benefit for preoperative beta-blocker use (OR, 0.97; 95% CI, 0.94-1.00; P = .093). Furthermore, the preoperative use of beta-blockers did not reduce the incidence of major postoperative complications, such as postoperative myocardial infarction, stroke, atrial fibrillation, reoperation, renal failure, prolonged ventilation, and sternal wound infection. ConclusionsOur study suggests that the use of preoperative beta-blockers did not reduce either operative mortality or the incidence of postoperative complications in patients undergoing CABG.

Are the benefits of beta blockers in cirrhotics only related to decreased portal hypertension?

Liver cirrhosis remains a leading cause of death worldwide. Non-selective beta blockers (NSBB) have played a key role in the treatment of portal hypertension since Lebrec’s pioneering observations that propranolol significantly reduces portal pressure in patients with cirrhosis (1). At first, the reduction in portal pressure was ascribed to a reduced splanchnic blood flow as a consequence of a demonstrated lowered cardiac output. However, further studies demonstrated that the portal hypertensive state is maintained despite the formation of collaterals because of splanchnic vasodilatation and increased portal venous inflow, the so called hyperdynamic circulation (2). NSBB are known to be more effective in patients presenting with clinical significant portal hypertension (CSPH, i.e., an HVPG >10 mmHg) in which the hyperdynamic circulation is more pronounced (3).

BETA BLOCKER POST ACS IN PATIENTS WITH PRESERVED LEFT VENTRICULAR SYSTOLIC FUNCTION

Background: The benefit of beta-blockers in the management of patients with heart failure and left ventricular systolic dysfunction is established; however, their role in patients whose post-MI course is without such complications, recurrent ischemia, or arrhythmia is less established. We

The effect of beta-blockers on mortality in heart failure with preserved ejection fraction: A meta-analysis of observational cohort and randomized controlled studies

BackgroundNearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality of patients with HF with preserved EF (HFpEF) is high. However, there is no therapy to improve survival in HFpEF. Although observational cohort studies (OCSs) have examined the survival benefit of beta-blockers in HFpEF, the results are inconsistent due to limited power with small sample sizes and/or lack of adjustment for known confounders. Furthermore, recent randomized controlled trial (RCT)s failed to show the mortality benefit of beta-blockers in HFpEF. However, these RCTs were not adequately powered and thus the definite conclusion cannot be drawn. Methods and resultsWe aimed to conduct a meta-analysis of the effect of beta-blockers on mortality in HFpEF. The search of electronic databases identified 5 OCSs with propensity score (PS) analysis (12,315 patients), 6 OCSs without PS analysis (15,275 patients), and 3 RCTs (1046 patients). Beta-blocker use was associated with improved survival in the pooled analysis of OCSs with PS analysis (RR [95% CI]=0.79 [0.66–0.95]) and in that of OCSs without PS analysis (0.70 [0.52–0.94]). In the pooled analysis of RCTs, beta-blocker use was associated with non-significant reduced risk for mortality (RR [95% CI]=0.80 [0.61–1.05]). Overall, use of beta-blockers reduced the risk of mortality by 21% (RR [95% CI]=0.79 [0.71–0.88]). ConclusionOur meta-analysis suggests the potential mortality benefit of beta-blockers in HFpEF. Well-designed and powered RCTs should be planned to confirm our observed potential survival benefit of beta-blockers in HFpEF.