β-Adrenergic Blocking Agents in Heart Failure

Bonet, Sergi; Escasany, Antònia Agustí; Arnau, Josep Maria; Vidal, Xavier; Diogène, Eduard; Galve, Enrique; Laporte, Joan‐Ramon

doi:10.1001/archinte.160.5.621

Cited by 77 publications

(15 citation statements)

References 49 publications

(113 reference statements)

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“…Thus, during local or global cardiac ischemia, the condition will be comparable to that induced by tyramine-stimulation, and inhibition of β 1 AR-mediated vasodilatation may disturb cardiac perfusion, particularly if combined with losartan, without having the desired effect on cardiac work load and cardiac energy consumption. This may explain why vasodilatory β-blockers reduced overall mortality with a greater effect than non-vasodilatory β-blockers such as atenolol (33). …”

Section: Discussionmentioning

confidence: 99%

Î²1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating Î²1-Adrenoceptors in Normotensive and Hypertensive Rats

Berg

2014

Front. Neurol.

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Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors, believed to involve the β2-subtype exclusively. However, β1-selective blockers are the most commonly used β-blockers in hypertension. Here the author tested the hypothesis that β1AR may function as presynaptic, release-facilitating auto-receptors. Since β1AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET), presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β1AR-selective antagonists (CGP20712A, atenolol, metoprolol) reduced norepinephrine overflow to plasma equally efficient as β2AR-selective (ICI-118551) and β1+2AR (nadolol) antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood–brain barrier, reduced norepinephrine overflow after adrenalectomy (AdrX), AdrX + ganglion blockade, losartan, or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β1AR, like β2AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1 receptor activation. β1AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β1AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Î²1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating Î²1-Adrenoceptors in Normotensive and Hypertensive Rats

Berg

2014

Front. Neurol.

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“…Though, the number of clinical trials that classified such patients accounts for <22% in our meta-analysis. Similarly, study of Bonet et al [43] reported no difference in mortality benefits among ischemic and non-ischemic heart disease and proposed greater benefit of vasodilating beta-blockers compared with the non-vasodilating agents particularly in patients with non-ischemic cardiomyopathy and attributed mortality benefits to significant reduction of pump failure and sudden death. Briefly, previous studies whether had not evaluated overall reduction of beta-blockers in the prevention of sudden cardiac death or need to be updated such as the studies of Bonet et al [43] and Heidenreich et al [40] as several recent and large randomized clinical trials have been carried out.…”

Section: Discussionmentioning

confidence: 99%

Beta-blockers for the prevention of sudden cardiac death in heart failure patients: a meta-analysis of randomized controlled trials

Al-Gobari

Khatib

Pillon

et al. 2013

BMC Cardiovasc Disord

116

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BackgroundIn many studies, beta-blockers have been shown to decrease sudden cardiac death (SCD) in heart failure patients; other studies reported mixed results. Recently, several large randomized control trials of beta blockers have been carried out. It became necessary to conduct a systematic review to provide an up-to-date synthesis of available data.MethodsWe conducted a meta-analysis of all randomized controlled trials examining the use of beta-blockers vs. placebo/control for the prevention of SCD in heart failure patients. We identified 30 trials, which randomized 24,779 patients to beta-blocker or placebo/control. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Eligible studies had to be randomized controlled trials and provide information on the incidence of sudden cardiac death in heart failure patients. Additional inclusion criteria included: treatment for >30 days and follow-up ≥ 3 months. Studies of patients <18 years, randomization to beta-blocker vs. an angiotensin converting enzyme (without placebo) and/or beta-blocker in both arms were excluded from the analysis. Pre-specified outcomes of interest included SCD, cardiovascular death (CVD), and all-cause mortality and were analyzed according to intention-to-treat.ResultsWe found that beta-blockers are effective in the prevention of SCD [OR 0.69; 95% CI, 0.62–0.77, P < 0.00001], cardiovascular death (CVD) [OR 0.71; 95% CI, 0.64–0.79, P < 0.00001], and all-cause mortality [OR 0.67; 95% CI, 0.59–0.76, P < 0.00001]. Based on the study analysis, 43 patients must be treated with a beta-blocker to prevent one SCD, 26 patients to prevent one CVD and 21 patients to prevent all-cause mortality in one year.ConclusionBeta-blockers reduce the risk of sudden cardiac death (SCD) by 31%, cardiovascular death (CVD) by 29% and all-cause mortality by 33%. These results confirm the mortality benefits of these drugs and they should be recommended to all patients similar to those included in the trials.

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“…The use of concomitant therapy with beta-adrenergic antagonists, a class of drugs with proven efficacy in the treatment of heart failure [34], [35], varied widely across trials, but was far from optimal. In only three trials [24], [28], [29] more than 50% of patients were taking beta-adrenergic antagonists in addition to ACE inhibitors and in only one small trial >90% were taking beta-adrenergic antagonists [29].…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Combined Therapy with Angiotensin Receptor Antagonists versus ACE Inhibitors Alone in Patients with Heart Failure

et al. 2010

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BackgroundThere is insufficient evidence whether the benefit of adding angiotensin II receptor blockers (ARBs) to angiotensin-converting enzyme (ACE) inhibitors outweighs the increased risk of adverse effects in patients with heart failure.Methodology/Principal FindingsTwo independent reviewers searched and abstracted randomized controlled trials of ARBs and ACE inhibitors compared to ACE inhibitor therapy alone in patients with heart failure reporting mortality and hospitalizations having a follow-up of at least 6 months identified by a systematic literature search. Eight trials including a total of 18,061 patients fulfilled our inclusion criteria. There was no difference between patients treated with combination therapy and ACE inhibitor therapy alone for overall mortality, hospitalization for any reason, fatal or nonfatal MI. Combination therapy was, however, associated with fewer hospital admissions for heart failure (RR 0.81, 95%CI 0.72–0.91), although there was significant heterogeneity across trials (p-value for heterogeneity = 0.04; I2 = 57% [95%CI 0–83%]). Patients treated with combination therapy had a higher risk of worsening renal function and symptomatic hypotension, and their trial medications were more often permanently discontinued. Lack of individual patient data precluded the analysis of time-to-event data and identification of subgroups which potentially benefit more from combination therapy such as younger patients with preserved renal function and thus at lower risk to experience worsening renal function or hyperkalemia.Conclusions/SignificanceCombination therapy with ARBs and ACE inhibitors reduces admissions for heart failure in patients with congestive heart failure when compared to ACE inhibitor therapy alone, but does not reduce overall mortality or all-cause hospitalization and is associated with more adverse events. Thus, based on current evidence, combination therapy with ARBs and ACE inhibitors may be reserved for patients who remain symptomatic on therapy with ACE inhibitors under strict monitoring for any signs of worsening renal function and/or symptomatic hypotension.

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β-Adrenergic Blocking Agents in Heart Failure

Cited by 77 publications

References 49 publications

Î²1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating Î²1-Adrenoceptors in Normotensive and Hypertensive Rats

Î²1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating Î²1-Adrenoceptors in Normotensive and Hypertensive Rats

Beta-blockers for the prevention of sudden cardiac death in heart failure patients: a meta-analysis of randomized controlled trials

Meta-Analysis of Combined Therapy with Angiotensin Receptor Antagonists versus ACE Inhibitors Alone in Patients with Heart Failure

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