Are beta2‐agonists responsible for increased mortality in heart failure?

Abstract

AimsPrevious large-scale, retrospective studies have shown increased mortality in heart failure (HF) patients using b2-agonists (B2As). We further examined the relationship between B2A use and mortality in a well-characterized population by adjusting for natriuretic peptide levels as a measure of HF severity. Methods and resultsThis was a retrospective cohort study of patients attending an HF Disease Management Programme with mean follow-up of 2.9 + 2.4 years. Chart review confirmed B2A use, dose and duration of use, and documented pulmonary function evaluation. The primary endpoint was the effect of B2A use compared with no B2A use on mortality using unadjusted and adjusted Kaplan2Meier survival curves. Data were available for 1294 patients (age 70.6 + 11.5 years) of whom 64% were male and 22.2% were taking B2As. b2-Agonist users were older, more likely to be male, to have smoked, to have chronic obstructive pulmonary disease (COPD) and asthma, and less likely to take beta-blockers. Multivariable associates of mortality included: B-type natriuretic peptide (BNP), coronary artery disease, age, and beta-blocker use. Unadjusted mortality rates for B2A users were found to be significantly higher than non-B2A users [hazard ratio (HR) 1.304, 95% confidence interval (CI) 1.030-1.652, P ¼ 0.028]. However, when adjusted for age, sex, medication, co-morbidity, smoking, COPD, and BNP differences, overall mortality rates were similar [HR 1.043, 95% CI (0.771 -1.412), P ¼ 0.783]. ConclusionUnlike previous reports, this retrospective evaluation of B2A therapy in HF patients shows no relationship with longterm mortality when adjusted for population differences including BNP. Large, prospective studies are required to define the risk/benefit ratio of B2As in patients with heart failure.--

Impact of beta2-agonists, beta-blockers, and their combination on cardiac function in elderly male patients with chronic obstructive pulmonary disease

“…Thus, these data may partly explain why there was no influence of β 2 -agonist use on outcome in our study patients. Bermingham et al10 reported that β 2 -agonist therapy in patients with HF showed no relationship with long-time mortality when adjusted for population differences, including BNP levels, which was in accordance with our results. These findings suggested that β 2 -agonists may be used safely in elderly male COPD patients.…”

“…Further analysis showed that combination therapy had no influence on all-cause mortality in the fully adjusted model. The results presented here are in line with a large-scale study, which also reported no increased risk of mortality in patients with HF taking both β-blockers and β 2 -agonists 10. Two studies that demonstrated that NT pro-BNP was associated with mortality36,37 were also consistent with our results.…”

“…A recent study observed no association between β 2 -agonist therapy and mortality in patients with heart failure (HF) after adjusting for B-type natriuretic peptide (BNP) 10. However, for COPD patients with coexisting HF, there is some concern regarding the relationship between β 2 -agonist use and mortality in patients with cardiovascular disease.…”

Hypertensive heart disease and bronchodilators: Potential left ventricular outflow obstruction

“…Prescription of bronchodilators in such circumstances is a common strategy, despite the ongoing controversies regarding the hazardous consequences this treatment can exert on morbidity and mortality [1,2]. The anticholinergic and beta 2 agonistic properties of bronchodilators are able to destabilize patients with various heart diseases, even if the latter are covered with beta blockers and other cardioprotective drugs [3].…”

“…Inhaled bronchodilators are frequently prescribed to patients with various forms of heart disease, when bronchospasm and wheezing coexist. The scenario in which these drugs are more extensively studied, is this of heart failure [1,2]. Harmful effects of bronchodilation related to secondary hypokalemia and arrhythmogenesis is a matter of vivid debate in this setting.…”