Risk of Mortality and Heart Failure Exacerbations Associated With Inhaled β-Adrenoceptor Agonists Among Patients With Known Left Ventricular Systolic Dysfunction

Abstract

Recent studies suggest that myocardial beta(2)-adrenoceptors may be important in chronic heart failure. We sought to determine if use of selective beta(2)-agonists was associated with hospitalization for heart failure and all-cause mortality. We studied a cohort of patients with left ventricular systolic dysfunction (LVSD). The outcome was the first hospitalization with a primary diagnosis of chronic heart failure or death from any cause. The exposure was the average number of beta-agonist canisters filled per month in the 90 days prior to and 15 days after enrollment. Among 1,529 subjects, the relative risk (RR) of chronic heart failure hospital admission associated with inhaled beta-agonists followed a dose-response relationship: RR for one canister per month, 1.4 (95% confidence interval [CI], 0.9 to 2.0), RR for two canisters per month, 1.7 (95% CI, 1.2 to 2.5), and RR for three canisters per month, 2.1 (95% CI, 1.4 to 3.1). The RR of death demonstrated a similar finding: RR for one canister per month, 0.9 (95% CI, 0.5 to 1.5), RR for two canisters per month, 1.3 (95% CI, 0.9 to 2.1), and RR for three canisters per month, 2.0 (95% CI, 1.3 to 3.1). Adjusting for potential confounding factors did not affect the estimates. Among subjects with LVSD, inhaled beta-agonists were associated with an increased risk of heart failure hospitalization, and all-cause mortality. Clinicians should carefully consider the etiology of dyspnea when prescribing beta-agonists to patients with LVSD.