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Risk of Heart Failure in Patients Using Beta Agonists

Am Fam Physician. 2004 Feb 1;69(3):697.

Chronic heart failure affects a significant number of persons in the United States. Recent studies have demonstrated that sympathetic activation is an important component of the pathophysiology in the progression of disease in patients with left ventricular systolic dysfunction. Serum catecholamine levels are elevated in patients with systolic dysfunction and cause a down-regulation of β1-adrenoceptors. Beta blockers antagonize these receptors and are used in the treatment of left ventricular systolic dysfunction because they have been shown to reduce myocardial mass, normalize ventricular shape, and improve left ventricular systolic function, functional status, and mortality. Standard treatment in patients with chronic pulmonary disease is inhaled beta2-agonists. These agents can have the opposite effect of beta blockers on the heart. Au and associates assessed a group of patients to see if the use of beta2-agonists had any impact on hospitalizations and mortality in patients with left ventricular dysfunction.

The study was of a cohort of patients who were seen in a Veterans Affairs health care system and had a cardiac ejection fraction of less than 45 percent, established by cardiac imaging examination. All patients were followed for at least one year after they entered the study. The outcomes evaluated were the first hospitalization with the primary diagnosis of chronic heart failure or death from any cause. Patients enrolled in the study had their pharmacy records reviewed for the filling of prescriptions for beta2-agonists from 90 days before to 15 days after study enrollment. Use of both canisters and nebulized beta2-agonists was recorded.

There were 1,529 patients enrolled in the study. The relative risk for hospitalization for chronic heart failure was 1.4 in those who used one canister of beta2-agonist, 1.7 in those who used two canisters, and 2.1 in those who used three canisters compared with those who did not use beta2-agonists.The relative risk of death in these patients followed a similar pattern. In those who received beta2-agonist by nebulizer, the relative risk for heart failure was 1.9,and the relative risk for death was 3.2. Adding in multiple comorbidity factors and cardiac medication use did not change these relative risks.

The authors conclude that patients with left ventricular systolic dysfunction who use an inhaled beta2-agonist have an increase in the risk for heart failure exacerbation and all-cause mortality. They add that patients with known left ventricular systolic dysfunction who are receiving high dosages of a beta2-agonist should assess the potential cause of this increase in use and consider that it may be a worsening of heart failure symptoms and not an exacerbation of pulmonary disease.

Au DH, et al. Risk of mortality and heart failure exacerbations associated with inhaled β-adrenoceptor agonists among patients with known left ventricular systolic dysfunction. Chest. June 2003;123:1964–9.


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