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Am Fam Physician. 2004;69(3):659-661

Chronic heart failure affects a significant number of persons in the United States. Part of the mechanism of this disease in patients with left ventricular systolic dysfunction is sympathetic activation. The latter leads to elevation of serum catecholamines, which then causes desensitization and downregulation of the β1-adrenoceptor. Beta blockers have been shown to have a positive impact on the heart and mortality rates in patients with left ventricular systolic dysfunction. Beta1-agonists, which have the opposite effect of beta blockers, are a cornerstone of treatment in patients with chronic obstructive pulmonary disease (COPD). Patients who have COPD and left ventricular systolic dysfunction depend on beta2 agonists for treatment of their lung disease, but these drugs may have a negative impact on the myocardial β2-receptors. Au and associates assessed the impact of selective beta2 agonists in patients with left ventricular systolic dysfunction.

Average number of canisters filled per monthCHF hospital admission (n = 391)No CHF hospital admission (n = 1,138)Unadjusted RR (95% CI)Adjusted RR(95% CI)
134831.4 (0.9 to 2.0)1.3 (0.9 to 2.0)
247921.7 (1.2 to 2.5)1.7 (1.2 to 2.5)
341662.1 (1.4 to 3.1)2.0 (1.3 to 3.0)

The trial was a cohort design of patients with left ventricular systolic dysfunction within a Veterans Affairs (VA) health system. Patients who received an echocardiogram or radionuclide study and had left ventricular systolic dysfunction were examined for the study. An additional inclusion criterion was that the patients must have filled at least one prescription within the VA system during the study period. Patients were assigned a start date and followed for one year. Demographic information, diagnoses, electronic progress notes from outpatient visits and hospitalizations, outpatient and inpatient pharmacy records, laboratory results, and radiographic studies were assessed. The average number of beta-agonist canisters dispensed by the VA pharmacy per month from 90 days before to 15 days after patients entered the study was determined. Primary outcome measures included the first hospitalization with a primary diagnosis of chronic heart failure and death from any cause.

A total of 1,529 patients were included in the final analysis. During the trial year, 26 percent were admitted for heart failure, and 16.9 percent died. The relative risk for hospital admission for heart failure in patients who filled prescriptions for an inhaled beta agonist followed a dose-response relationship. Patients who filled prescriptions for one canister per month had an unadjusted relative risk of 1.4; those who filled prescriptions for two canisters per month had a relative risk of 1.7; and those who filled prescriptions for three canisters per month had a relative risk of 2.1 (see the accompanying table).

The relative risk for death followed the same dose-response curve; patients who filled prescriptions for three or more canisters per month had a relative risk of death during the study period of 2.0. When all potential confounding variables were adjusted for during the analysis, there was no impact on the relative risks.

The authors conclude that the use of an inhaled beta agonist in patients with left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality and hospitalization for heart failure. They add that physicians should be careful when determining the cause of dyspnea in patients with left ventricular systolic dysfunction. Patients who are taking high dosages of a beta agonist should be reassessed to determine if the increased use is related to lung disease or to exacerbation of heart failure.

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