DH Au, VA Puget Sound Health Care System; JR Curtis, University of Washington; MB McDonell, VA Puget Sound Health Care System; E Udris, VA Puget Sound Health Care System; SD Fihn, VA Puget Sound Health Care System

Objectives: Cardiovascular and obstructive pulmonary diseases are both commonly present in elderly men. Beta-blockers decrease mortality and hospital admissions resulting from congestive heart failure (CHF) while inhaled beta-2-agonists, used in the treatment of obstructive lung disease, have an opposing pharmacologic effect. In oral form, long acting beta-agonists have been associated with an increased risk of hospitalization for CHF. However,little data exists examining the association between short-acting inhaled beta-agonists and the risk of hospitalization for congestive heart failure. Our objective was to examine the association between inhaled beta-2-agonists delivered by metered-dose inhalers and subsequent hospital admission for CHF.

Methods: We performed a nested case-control study using data from the Ambulatory Care Quality Improvement Project (ACQUIP). To be eligible for ACQUIP, patients must have been enrolled in one of 7 VA General Internal Medicine clinics during the 12 months prior to study entry and have been assigned a primary care provider. Cases in this present analysis were patients who had a primary ICD-9 discharge diagnosis of CHF (ICD9 428.x and 398.91). Controls were frequency matched by site and index date at a ratio of 1:18. Exposure to beta-agonist MDI was measured as the number of beta-agonist canisters filled during the 90 days prior to the index date. For cases, the index date was the date of their hospitalization for CHF. Control patients were randomly assigned an index date . Potential confounding variable were derived from outpatient and inpatient discharge diagnoses prior to the index date.

Results: Of the 34,103 subjects who were enrolled at the initiation of ACQUIP, we identified 782 cases who had been admitted to a VA medical center with a primary discharge diagnosis of CHF and 12,230 controls. The unadjusted odds ratios for admission due to CHF was elevated for each stratum of beta-agonist exposure {1-2 MDI [OR 2.64 (1.98, 3.53)], 3 or more MDI [OR 2.36 (1.72, 3.25)]}. After adjusting for the presence of cardiovascular disease, COPD, HTN, age, diabetes and ACE inhibitor use, the odds ratios for each exposure level were 1.46 (1.02, 2.09) and 1.29 (0.87, 1.93) respectively. Stratifying the analysis on whether a subject was prescribed a beta-blocker during the same 90-day period demonstrated that, among patients who used beta-blockers, beta-agonist use increased the odds of a hospitalization for CHF {Adjusted OR's, 1-2 MDI [1.27 ( 0.67, 2.46)], 3 or more [2.57 (1.22, 5.41)]}. Among subjects that did not use beta-blockers, beta-agonist were not associated with an elevated risk of hospitalization for CHF.

Conclusions: Inhaled short acting beta-agonists are associated with an increased risk of hospitalization for congestive heart failure. This effect is most pronounced among patients who also use beta-blockers. These results are hypothesis generating and suggest further studies should explore the hypothesis that beta-agonist use may precipitate exacerbations of CHF.

Impact: If the results that this study suggests are confirmed, then inhaled beta-agonists would need to be prescribed cautiously to patients with congestive heart failure.