Beta-blocker Group Research Articles

Effect of beta-blocker therapy on early mortality after emergency colonic cancer surgery.

Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery. This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis. A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin. Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.

Long-term use of carvedilol in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

BackgroundDespite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI).Methods and resultsIn a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06)ConclusionLong-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI.Trial registrationCAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.

EFFECT OF BETA BLOCKERS ON NOCTURNAL ARRHYTHMIAS AND HEART RATE VARIABILITY IN OBSTRUCTIVE SLEEP APNOEA PATIENTS

Objective: To explore the effects of BB on nocturnal peri-apnoeic heart rate variability (HRV) and on arrhythmias in OSA patients. Design and method: Arrhythmias and increased cardiovascular V are highly prevalent in patients with obstructive sleep apneas (OSA), possibly resulting in fatal events, as showed by the significant increase of sudden cardiac death and arrhythmias during sleep in OSA patients. Data concerning drug effects on this phenomenon are scarce and the use of beta blockers (BB) has been limited by the concern that they might lead to bradyarrhythmias. However, recent evidence suggests that BB mostly reduce rhythm accelerations with trivial influence on decelerations. We enrolled 166 OSA patients (78 BB-treated and 88 BB-naïve), who performed cardiorespiratory polysomnography (PSG) between 2013 and 2015. Patients on antiarrhythmic therapy were excluded. We analysed PSG-derived ECG traces for the assessment of arrhythmias. Moreover, through an ad hoc developed software, we performed a specific analysis of HRV associated with apnoeic events. We considered HR decelerations occurring during the apnoeic phase and accelerations during the post-apnoeic phase (the first five seconds after the resumption of breathing). Statistical analysis was performed with Mann-Whitney U test. Results: We did not find any difference between BB-treated and BB-naïve groups concerning prevalence of nocturnal arrhythmias. HRV analysis showed a reduction of HR accelerations, expressed as RR length, during post-apnoeic phase in BB group (940.7 ± 121.4msec BB-treated vs 897.8 ± 122.5msec BB-naïve; P = 0.040). Moreover, BB-treated patients showed a smaller delta between HR decelerations/accelerations and mean HR during apnoeic phase (58.5 ± 28.5 vs 74.6 ± 40.2msec; P = 0.010 and75.0 ± 42.4 vs 96.7 ± 55.5msec; P = 0.018, respectively). Finally, the delta between HR accelerations and decelerations was smaller in BB-treated group (133.5 ± 63.8 vs 171.3 ± 87.7msec; P = 0.010). Conclusions: BB therapy does not worsen apnoea-induced HR decelerations nor increase the risk of bradyarrhythmias, while reducing the frequency and magnitude of apnoea-induced HR acceleration. Therefore, our study suggests that BB are safe and possibly advantageous in OSA patients, although further studies are needed to establish if in the long term they may have a role in reducing fatal events.

Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy.

Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69bpm. All-cause mortality during the median follow-up of 42.8months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p < 0.001). Survival for group A patients with a HR ≥ 70bpm was 28.8% but 14.8% if HR was 50-70bpm (p = 0.054). Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.

FIVE-YEAR DYNAMICS OF SECONDARY PREVENTION IN PATIENTS WITH STABLE ANGINA AT SPECIALIZED OUT-PATIENT LEVEL IN MOSCOW (PHARMACOEPIDEMIOLOGY STUDY)

Aim. To assess five-year trend in terms of specialists’ adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina on the level of out-patient specialized healthcare institution in Moscow. Material and methods. Two-stage retrospective pharmacoepidemiological study was conducted. The object of the study – patient medical records. At the first stage of the study medical records of 2915 patients with stable angina visited the healthcare institution for the first time in 2006 were included, at the second stage – medical records of 1633 patients with stable angina with primary visit in 2011. Results. Over the five-year period prescription rates of drugs improving prognosis in patients with stable angina significantly increased: antiplatelets – up to 82.7%, beta-blockers – up to 74.3%, statins – up to 45.6%. Despite of no changes registered in prescription rate of the ACE inhibitors, marked increase up to 14.7% in prescription rate of angiotensin receptor blockers was revealed. In the prescription structure of pharmacological groups changes were detected concerning the preferred choice of a specific drug. Due to implementation of dual antiplatelet therapy into clinical practice a reduced number of recommendations of acetylsalicylic acid as monotherapy (down to 93.0%) and increased – in combination with clopidogrel (up to 5.4%) was registered at the second stage of the study. Over a five-year period bisoprolol (55.0%) occupied the leading position in the group of beta-blockers. Metoprolol’s prescription rate decreased to 27.4%. Prescription rate of atenolol decreased down to 3.1%, while that of nebivolol increased up to 8.3%. When choosing among statins specialists recommended significantly more often atorvastatin (up to 52.9%). In the group of ACE inhibitors three drugs preserved their leading positions. Meanwhile the number of recommendations of enalapril increased up to 50.8%, perindopril – up to 24.1%. Analysis of prescribed doses revealed significant increase in recommendations of specific drugs in higher daily doses: acetylsalicylic acid 100 mg – up to 71.1%, simvastatin and atorvastatin 20 mg – up to 60.5% and 41.9%, respectively. When prescribing beta-blockers and ACE inhibitors specialists continued to use minimal and medium therapeutic doses, possibly due to dose titration in patients with comorbidities. Conclusion. Study results demonstrated positive trend in terms of specialists’ adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina. However, a number of problem aspects were identified that require further optimization of medical and preventive measures in healthcare institutions.

Effect of Beta-blocker Treatment on V˙O2peak in Patients with Heart Failure.

In addition to prolonged life and reduced hospitalization rates, it is currently unclear whether beta-blocker (BB) treatment modulates peak oxygen consumption (V˙O2peak), a hallmark of exercise capacity, in patients with heart failure (HF). The main aim of this study is to determine the effect of BB treatment on V˙O2peak in HF patients. We conducted a systematic search of MEDLINE, Scopus, and Web of Science since their inceptions until March 2017 for randomized controlled trials (RCT) assessing the effect of BB treatment on V˙O2peak in chronic HF patients. A meta-analysis was performed to ascertain the standardized mean difference (SMD) between the effects of BB and placebo treatment on V˙O2peak. Secondary outcomes included peak exercise performance and New York Health Association functional class. Subgroup and meta-regression analyses assessed potential moderating factors. Fourteen RCT met the inclusion criteria (overall n = 616). Interventions comprised BB (n = 324) or placebo (n = 292) administration lasting 3 to 24 months. Concomitant reported medication did not differ between HF patients assigned to BB and placebo groups. After data pooling, V˙O2peak was preserved with BB compared with placebo treatment (SMD, -0.04; 95% confidence interval (CI), -0.20 to 0.12; P = 0.61); heterogeneity among studies was not detected (I = 0%, P = 0.88). Peak exercise performance was not altered (SMD, 0.02; 95% CI, -0.16 to 0.20; P = 0.85), whereas New York Health Association functional class was reduced with BB compared with placebo (SMD, -0.54; 95% CI, -0.90 to -0.18; P = 0.003). According to evidence from RCT, prolonged BB (B1-selective or nonselective) treatment does not affect V˙O2peak but improves functional status in HF patients.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

Efficacy of Ivabradine in Combination with Beta-Blockers Versus Uptitration of Beta-Blockers in Patients with Stable Angina (CONTROL-2 Study).

IntroductionHeart rate (HR) reduction is an integral part of antianginal therapy, but many patients do not reach the guideline-recommended target of less than 60 bpm despite high use of beta-blockers (BB). Failure to uptitrate BB doses may be partly to blame. To explore other options for lowering HR and improving angina control, CONTROL-2 was initiated to compare the efficacy and tolerability of the combination of BBs with ivabradine versus uptitration of BBs to maximal tolerated dose, in patients with stable angina.MethodsThis multicenter, open, randomized study included 1104 patients with Canadian Cardiovascular Society (CCS) class II or III stable angina, in sinus rhythm, and on background stable treatment with non-maximal recommended doses of BBs. Consecutive patients were allocated to ivabradine + BB or BB uptitration in a 4:1 ratio.ResultsAt the end of the study (week 16), addition of ivabradine to BB treatment and BB uptitration resulted in reduction in HR (61 ± 6 vs. 63 ± 8 bpm; p = 0.001). At week 16, significantly more patients on ivabradine + BB were in CCS class I than with BB uptitration (37.1% vs. 28%; p = 0.017) and significantly more patients were angina-free (50.6% vs. 34.2%; p < 0.001). Patient health status based on the visual analogue scale (VAS) was also better in the ivabradine + BB group. Adverse events (AEs) were significantly more common with BB uptitration than with the ivabradine + BB combination (18.4% vs. 9.4%, p < 0.001).ConclusionIn patients with stable angina, combination therapy with ivabradine + BB demonstrated good tolerability, safety, and more pronounced clinical improvement, compared to BB uptitration.Trial RegistrationISRCTN30654443.FundingServier.

Use of Beta-Blockers on Maintenance Dialysis Patients and Ischemic Cerebral and Cardiovascular Deaths: An Examination Using Propensity Score.

Beta-blockers are frequently used in dialysis patients because of their cardioprotective properties. However, the effect of beta-blockers on reducing dialysis mortality has not been sufficiently examined to date. Thus, we sought to examine the effects on cardiovascular prognosis of beta-blockers using our outpatient dialysis database. From 389 dialysis patients registered in our database, subjects taking beta-blockers were extracted and matched with patients not taking beta-blockers using propensity scores based on 39 variables. Cardiovascular mortality, mortality of heart failure/sudden cardiac death, and mortality of ischemic cerebral and cardiovascular death were estimated using Kaplan-Meier method, and a log-rank test was used to analyze the difference between these survival curves for significance. A total of 216 patients, 108 matched pairs, were extracted from the whole cohort. There was no difference in background factors between the two groups. During mean observation periods of 4.4 years, 76 patients died, including 51 cases of cardiovascular death. Cardiovascular deaths included 30 heart failure/sudden deaths and 13 ischemic cerebral and cardiovascular deaths. For both cardiovascular and heart failure/sudden death, the survival curves did not indicate a significant difference between the 2 groups. On the contrary, in case of ischemic cerebral and cardiovascular deaths, 11 patients died in the beta-blocker group, with a significantly poor prognosis observed in the survival curve (p = 0.0132). Through the use of beta-blockers, a significant increase in ischemic cerebral and cardiovascular deaths was observed. The administration of beta-blockers to dialysis patients was found to worsen the cardiovascular prognosis, so sufficient examination will be needed in the future.

Effects of Bisoprolol Are Comparable with Carvedilol in Secondary Prevention of Acute Myocardial Infarction in Patients Undergoing Percutaneous Coronary Intervention.

Although the benefits of carvedilol have been demonstrated in the era of percutaneous coronary intervention (PCI), very few studies have evaluated the efficacy of bisoprolol in the secondary prevention of acute myocardial infarction (MI) in patients treated with PCI. We hypothesized that the effect of bisoprolol would not be different from carvedilol in post-MI patients. A total of 13,813 patients who underwent PCI were treated either with carvedilol or bisoprolol at the time of discharge. They were enrolled from the Korean Acute MI Registry (KAMIR). After 1:2 propensity score matching, 1,806 patients were enrolled in the bisoprolol group and 3,612 patients in the carvedilol group. The primary end point was the composite of major adverse cardiac events (MACEs), which was defined as cardiac death, nonfatal MI, target vessel revascularization, and coronary artery bypass surgery. The secondary end point was defined as all-cause mortality, cardiac death, nonfatal MI, any revascularization, or target vessel revascularization. After adjustment for differences in baseline characteristics by propensity score matching, the MACE-free survival rate was not different between the groups (HR=0.815, 95% CI:0.614–1.081, p=0.156). In the subgroup analysis, the cumulative incidence of MACEs was lower in the bisoprolol group in patients having a Killip class of III or IV than in the carvedilol group (HR=0.512, 95% CI: 0.263–0.998, p=0.049). The incidence of secondary end points was similar between the two beta-blocker groups. In conclusion, the benefits of bisoprolol were comparable with those of carvedilol in the secondary prevention of acute MI.

Ivabradine has a neutral effect on mortality in randomized controlled trials.

Background:It has long been a controversial hotspot whether resting heart rate (RHR) is a risk factor or a marker for death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, is a pure RHR lowering agent. The study was aimed to investigate whether ivabradine would reduce more RHR, cardiovascular disease (CVD) mortality, and all-cause mortality than those placebo or beta-blockers.Methods:The authors performed a meta-analysis of 8 randomized controlled clinical studies (with 40,357 participants), and 3 studies of those which were ivabradine versus placebo (36,069 participants) and other 5 studies ivabradine versus beta-blockers (4288 participants) were available. The authors compared the association of the RHR reduction with death from CVD causes (2674 in 40,285 participants) and the rate of all-cause death (3143 deaths in 38,037 participants), and assessed improvement in death rates with the use of ivabradine.Results:The change of RHR from baseline to endpoint was 8 to 16 beats/min (bpm) in ivabradine group, 1 to 8 bpm in placebo group, and 4 to 24 bpm in beta-blockers group. In ivabradine versus placebo, the reduced risks of CVD mortality and all-cause morbidity were not significantly (risk ratio [RR] 1.02; 95% confidence interval [CI] 0.91–1.14, P = .737; RR: 1.00, 95% CI: 0.92–1.09, P = .992, respectively). CVD and all-cause morbidity were similar for ivabradine versus beta-blockers (RR: 1.04; 95% CI: 0.80–1.37, P = .752; RR: 1.17, 95% CI: 0.53–2.60, P = .697, respectively).Conclusions:Ivabradine had a neutral effect on mortality, suggesting that a pure RHR lowering agent did not reduce CVD mortality, all-cause mortality and improve the lifespan.

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. Participants taking beta-blockers (n=28) had a lower ventilatory threshold (P<.01) and peak oxygen uptake (P=.02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P=.04). The oxygen uptake efficiency slope was not impacted by beta-blocker use. Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population.

A prospective study of various anti hypertensive drugs on reversal of left ventricular hypertrophy in hypertensive Bangladeshi population

Regression of ventricular hypertrophy is the restoration of normal ventricular structure and physiology after the hypertrophy has developed. It has been clearly demonstrated that once left ventricular hypertrophy (LVH) is diagnosed, it represents a strong blood pressure independent risk factor for cardiovascular morbidity and mortality.This prospective observational study was carried out in Department of Cardiology, BSMMU, Dhaka to compare the effectiveness of different anti-hypertensive agents in reducing left ventricular hypertrophy (LVH) in hypertensive Bangladeshi population involving 95 patients with clinically diagnosed hypertension. The duration of study was from July 2005 to Tune 2008. Out of these 95 patients, 20 were included in beta-blocker(BB) group, 14 in angiotensin converting enzyme inhibitor(ACEi) group, 20 in beta-blocker(BB) + diuretic(DD) group, 14 in angiotensin converting enzyme inhibitor(ACEi) + diuretics(DD) group, 13 in beta-blocker(BB) and angiotensin enzyme inhibitor(ACEi) group and 14 in beta-blocker(BB) + angiotensin converting enzyme inhibitor(ACEi) + diuretic(DD) group. patients were followed-up at 8 weeks, 6 months, 1 year and at 2 years. A baseline M-mode echocardiography was done to document LVH. Among three groups of anti-hypertensive drugs, angiotensin converting enzyme inhibitor alone has been found to be most effective as compared to beta blockers when used alone than in combination groups (Beta blocker plus ACEi plus Diuretics or Beta blocker plus ACEi). Although, statistically not significant, a clear benefit has been shown in all groups in terms of LVH regression.Bangladesh Med J. 2016 Sep; 45 (3): 156-159

Intravenous beta-blocker therapy in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention is not associated with benefit regarding short-term mortality: a Swedish nationwide observational study.

Our aim was to investigate the impact of intravenous (IV) beta-blocker therapy on short-term mortality and other in-hospital events in patients with ST-segment elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) and primary percutaneous coronary intervention (PCI). Using the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we identified all patients with STEMI undergoing PCI between 2006 and 2013. Patients with cardiogenic shock and cardiac arrest at presentation were excluded. The primary endpoint was mortality within 30 days. Secondary endpoints were in-hospital events (mortality, cardiogenic shock and left ventricular ejection fraction [LVEF] <40% at discharge). We adjusted for confounders with a multivariable model and propensity score matching. Out of 16,909 patients, 2,876 (17.0%) were treated with an IV beta-blocker. After adjusting for confounders, the IV beta-blocker group had higher 30-day all-cause mortality (HR: 1.44, 95% CI: 1.14-1.83), more in-hospital cardiogenic shock (OR: 1.53, 95% CI: 1.09-2.16) and were more often discharged with an LVEF <40% (OR: 1.70, 95% CI: 1.51-1.92). In this large nationwide observational study, the use of IV beta-blockers in patients with STEMI treated with primary PCI was associated with higher short-term mortality, lower LVEF at discharge, as well as a higher risk of in-hospital cardiogenic shock.

Effects of preadmission beta-blockers on neurogenic stunned myocardium after aneurysmal subarachnoid hemorrhage: A meta- analysis

ObjectiveSpontaneous subarachnoid hemorrhage is mostly caused by the rupture of an aneurysm. Neurogenic stunned myocardium (NSM) is one of the most frequent complications caused by aneurysmal subarachnoid hemorrhage (aSAH). The possible pathogenesis of NSM may be that the catecholamine peak resulting from aSAH leads to subendocardial ischemia or coronary artery spasm. We designed this meta-analysis to find out whether beta-blockers (BB) can significantly reduce the incidence of NSM and improve the outcomes of aSAH. Patients and methodsWe systematically searched PubMed, Embase, Cochrane library, Elsevier and Medline from inception to Feb 2016. All studies related to the preadmission beta-blocker with aSAH were included. ResultsThree retrospective studies and 691 patients were included. The incidence of mortality [OR=0.68, 95%CI (0.08–3.50), P=0.57], cardiac dysfunction [OR = 0.55, 95% CI (0.05–6.49), P=0.63], cerebral vasospasm (OR=0.52 95% CI(0.18–2.56), P=0.50] had no statistical difference between the preadmission BB group and no BB group. ConclusionThe preadmission beta-blocker cannot decrease the incidence of mortality, cardiac dysfunction, cerebral vasospasm in patients with aSAH. A further research of the usefulness of preadmission beta-blocker in patients with aSAH will be needed.

Abstract 302: The PAT Ratio is Reduced by Beta-blockers

Background: Flow-mediated dilatation (FMD) of the brachial artery and Peripheral arterial tonometry (PAT) are both methods for assessing endothelial vascular function. FMD measures predominantly nitric oxide mediated vasodilation whereas PAT measures a more complex range of mechanisms. The recent study showed that the sympathetic nervous system plays a significant role in this response. Methods: The study involved 176 subjects (mean age66 ±12 years). Based on the medication of beta-blockers, they were divided into 2 groups: beta-blocker group (n=37) and control group (n=139). Flow mediated vasodilatation (FMD) and nitroglycerine-induced vasodilatation (NID) in the brachial artery was measured by using UNEXEF18G (UNEX CO, Japan), and nitroglycerin mediated vasodilatation (NMD) was used as a control test for FMD. At the same time, PAT ratio was measured by using Endo-PAT 2000 (Itamar Medical, Israel) Results: PAT ratio was significantly impaired in beta-blocker group compared to that in control group (1.5±0.4% vs. 1.9±0.6%, respectively; P&lt;0.05). However, FMD and NMD had no deference in both groups. Multivariable analysis revealed that blood sugar and medication of beta-blockers were independent variables for PAT ratio. Conclusion: These result show that beta-blockers is associated with a tendency towards reduced PAT ratio. PAT needs to be further studied, including the assessment of non-endothelial factor

P716 Beta-blocker use is associated with a higher relapse risk of inflammatory bowel disease – a Dutch retrospective cohort study

Background: Inflammatory bowel disease (IBD) is a multifactorial disease and as such, many factors may influence the disease course – like the concomitant use of medication. One such drug group is beta-blockers, a medication group primarily prescribed for the treatment of cardiovascular disease, which is used by approximately 10% of the Dutch population. Beta-blockers block the β-adrenergic receptors. β-adrenergic receptor activation has potent anti-inflammatory effects on the myeloid compartment of the immune system. In this pilot study, we addressed whether an association exists between the use of beta-blockers and the course of IBD, as defined by the risk of a disease relapse in patients with IBD. Methods: In this retrospective cohort study design, we used a population-based IBD cohort of 1461 patients. We identified relapses using medication prescriptions as a proxy. We calculated the number of relapses per 100 person-years and compared this between IBD patients using beta-blockers and IBD patients not using beta-blockers. We used Cox proportional hazards models with shared frailty to compare the risk of a relapse between both groups. Results: 250 IBD patients had available prescriptions and were included in the study, 30 patients (12%) used a beta-blocker. In the beta-blocker group, there were 21 relapses per 100 person-years (95% confidence interval (CI): 14.0–28.6) versus 29 relapses per 100 person-years (95% CI: 26.2–32.4) in the group of patients that did not use a beta-blocker. However, when we used the Cox proportional hazard model with shared frailty and adjusted for age and gender we observed a 54% higher risk of a relapse in the group of IBD patients that used a beta-blocker versus the IBD patients that did not use a beta-blocker (adjusted hazard ratio: 1.54, 95% CI: 1.05–2.25; p=0.03). Conclusions: The results of our study suggest that beta-blocker use is associated with an increased risk of disease relapses in patients with IBD. Indeed, concomitant medication use seems to be one of the factors that can influence the course of IBD and this should be acknowledged while making decisions about treatment of IBD and follow-up. These results warrant confirmation in a larger cohort.

Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy.

Objective. To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods. In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results. The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5 ± 2.5 mmHg and 22.2 ± 2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7 ± 3.1 mmHg and 16.1 ± 3.1 mmHg, respectively, in TTFC group and 21.1 ± 3.1 mmHg and 16.1 ± 2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (−4.6 mmHg; one-sided 95% confidence interval [−inf, −3.9]; p < 0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion. Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391.

SYSTEMIC BETA-BLOCKERS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To evaluate whether oral beta-blockers (BBs) are associated with a decreased number of intravitreal injections in patients with incident neovascular age-related macular degeneration. A retrospective cohort study of subjects with a new diagnosis of neovascular age-related macular degeneration was conducted using a medical claims database from a large national US insurer. Two cohorts were created for comparison consisting of patients with regular use of BBs or calcium channel blockers. The main outcome measured was the difference in the mean number of intravitreal injections administered between the two cohorts. After inclusion and exclusion criteria, 239 BB and 155 calcium channel blocker subjects remained for analysis. Univariate analysis revealed that the mean number of injections in the BB cohort was 6.43 (95% confidence interval [CI] 5.90-6.95) versus 6.55 (95% CI 5.85-7.25) in the calcium channel blocker cohort (P = 0.78). After multivariate adjustment, the mean number of injections in the BB group was 6.32 (95% CI 5.77-6.87) versus 6.71 (95% CI 6.02-7.40) in the calcium channel blocker group. The overall difference between the 2 groups was -0.39 (95% CI difference -1.29 to 0.51; P = 0.40). The use of oral BBs is not associated with a decreased number of intravitreal injections in incident neovascular age-related macular degeneration patients.

Ivabradine in the treatment of systolic heart failure - A systematic review and meta-analysis.

AIMTo perform a systematic-review and meta-analysis to compare outcomes of ivabradine combined with beta-blocker to beta-blocker alone in heart failure with reduced ejection fraction (HFrEF).METHODSWe searched PubMed, Cochrane, EMBASE, CINAHL and Web of Science for trials comparing ivabradine + beta-blocker to beta-blocker alone in HFrEF. We performed a systematic-review and meta-analysis of published literature. Primary end-point was combined end point of cardiac death and hospitalization for heart failure.RESULTSSix studies with 17671 patients were included. Mean follow-up was 8.7 ± 7.9 mo. Combined end-point of heart failure readmission and cardiovascular death was better in ivabradine + beta-blocker group compared to beta-blocker alone (RR: 0.93, 95%CI: 0.79-1.09, P = 0.354). Mean difference (MD) in heart rate was higher in the ivabradine + beta-blocker group (MD: 6.14, 95%CI: 3.80-8.48, P < 0.001). There was no difference in all cause mortality (RR: 0.98, 95%CI: 0.89-1.07, P = 0.609), cardiovascular mortality (RR: 0.99, 95%CI: 0.86-1.15, P = 0.908) or heart failure hospitalization (RR: 0.87, 95%CI: 0.68-1.11, P = 0.271).CONCLUSIONFrom the available clinical trials, ivabradine + beta-blocker resulted in a significantly greater reduction in HR coupled with improvement in combined end-point of heart failure readmission and cardiovascular death but with no improvement in all cause or cardiovascular mortality. Given the limited evidence, further randomized controlled trials are essential before widespread clinical application of ivabradine + beta-blocker is advocated for HFrEF.