Bronchodilator use is a powerful independent predictor of worsening heart failure (HF) and increased mortality in a broad spectrum of patients with HF, according to the CHARM trial results published online July 9 in the European Journal of Heart Failure.
HF and chronic obstructive pulmonary disease (COPD) are common partners. Bronchodilators are associated with adverse cardiovascular outcomes in patients with pulmonary disease. However, the study authors noted that the outcome of patients with HF prescribed bronchodilators is poorly defined.
In CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) trial, Nathaniel M. Hawkins, MD, from the Liverpool Heart and Chest Hospital in Liverpool, England, and colleagues randomized 7,599 patients with symptomatic HF to receive candesartan (Atacand, AstraZeneca) or placebo. They examined the relative risk conveyed by bronchodilator therapy 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 percent), according to the authors. Beta-blocker utilization was markedly lower in patients receiving bronchodilators compared with those without (overall 31.9 vs. 57.6 percent).
Bronchodilator use was associated with increased all-cause mortality [hazard ratio (HR) 1.26], cardiovascular death [HR 1.21], HF hospitalization [HR 1.49] and major adverse cardiovascular events [HR 1.32], the researchers said.
Hawkins and colleagues reported the adverse outcomes were consistent in patients with reduced and preserved systolic function; and no significant interaction was observed between bronchodilators and beta-blockade with respect to outcomes.
The authors designated the diversity and magnitude of adverse outcomes associated with bronchodilator therapy as “surprising.” Cohorts defined by bronchodilator prescription represent a heterogeneous group of patients: COPD, asthma, restrictive lung disease and those misdiagnosed with airflow obstruction. The latter is common in patients with decompensated HF, in whom interstitial edema causes airway compression and bronchial hyper-responsiveness, according to the authors.
“Non-cardiovascular deaths are inevitable in cohorts dominated by pulmonary disease,” they wrote. “The excess cardiovascular mortality is more concerning. Bronchodilators were associated with a 40 percent higher risk of death due to progressive pump failure. The risk of hospitalization for worsening HF was likewise 49 percent greater.”
Whether this relates to a toxic effect of bronchodilators, underlying pulmonary disease or both is unclear and warrants further investigation, concluded the authors, adding that there are "many challenges for future research."