Baseline Characteristics and Outcomes of Patients with Heart Failure Receiving Bronchodilators in the CHARM Programme

Nathaniel M. Hawkins; Duolao Wang; Mark C. Petrie; Marc A. Pfeffer; Karl Swedberg; Christopher B. Granger; Salim Yusuf; Scott D. Solomon; Jan Östergren; Eric L. Michelson; Stuart J. Pocock; Aldo P. Maggioni; John J.V. McMurray

Disclosures

Eur J Heart Fail. 2010;12(6):557-565. 

In This Article

Abstract and Introduction

Abstract

Aims Heart failure (HF) and chronic obstructive pulmonary disease are common partners. Bronchodilators are associated with adverse cardiovascular outcomes in patients with pulmonary disease. The outcome of patients with HF prescribed bronchodilators is poorly defined.
Methods and results The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomized 7599 patients with symptomatic HF to receive candesartan or placebo. The relative risk conveyed by bronchodilator therapy was examined using a multivariable Cox proportional hazards model. The prevalence of bronchodilator therapy was similar in patients with reduced and preserved systolic function (respectively, 8.7 vs. 9.2%, P = 0.46). Beta-blocker utilization was markedly lower in patients receiving bronchodilators compared with those without (overall 31.9 vs. 57.6%, P < 0.0001). Bronchodilator use was associated with increased all-cause mortality [HR 1.26 (1.09–1.45), P = 0.0015], cardiovascular death [HR 1.21 (1.03–1.42), P = 0.0216], HF hospitalization [HR 1.49 (1.29–1.72), P < 0.0001], and major adverse cardiovascular events [HR 1.32 (1.17–1.76), P < 0.0001]. The adverse outcomes were consistent in patients with reduced and preserved systolic function. No significant interaction was observed between bronchodilators and beta-blockade with respect to outcomes.
Conclusion Bronchodilator use is a powerful independent predictor of worsening HF and increased mortality in a broad spectrum of patients with HF. Whether this relates to a toxic effect of bronchodilators, underlying pulmonary disease, or both is unclear and warrants further investigation.

Introduction

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common partners with common problems.[1] Remarkably few studies have addressed this intersection between cardiovascular and pulmonary disease. The combination presents diagnostic challenges,[1] limits the use of beta-blockers,[2] and is associated with worse survival.[1] The causes of higher mortality have been studied in a very limited fashion.[3] Use of bronchodilators, both beta-agonist and anticholinergic, is associated with adverse cardiovascular outcomes in patients with pulmonary disease.[4–8] The prognosis of patients with HF prescribed bronchodilators is however ill defined.[9,10] In particular, there is little information regarding the prevalence of bronchodilator use in HF with and without systolic dysfunction, or the relationship between bronchodilator use and outcomes. In the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, candesartan significantly reduced cardiovascular deaths and hospital admissions for HF.[11] The CHARM programme provides a unique opportunity to examine the prevalence and prognostic implications of bronchodilator use in a large cohort of patients with HF and wide range of left ventricular ejection fraction (LVEF).

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