Risk of mortality and heart failure exacerbations associated with inhaled β-adrenoceptor agonists among patients with known left ventricular systolic dysfunction

Objectives: 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. Methods: 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 R-agonist canisters filled per month in the 90 days prior to and 15 days after enrollment. Results: 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, Conclusion: 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.