Abstract 971: Beta Adrenergic Agonists and Sudden Death in Coronary Artery Disease
Background: Recent observations have raised concerns regarding the cardiovascular safety of beta-adrenergic agonists, especially in patients with heart disease. At least one initial study indicated potential for increased risk of sudden cardiac death (SCD) but systematic evaluation of mechanisms has not been performed.
Methods: Using a case-control design matched for coronary artery disease, we evaluated the potential role of beta agonists as determinants of SCD risk in a prospective, multiple source study of one million residents of a northwestern US metro area. Analysis was limited to cases and controls with medication information available along with a 12-lead ECG, prior to and unrelated to the acute event for case subjects. Bivariate comparisons were made using independent-samples t tests and Pearson’s χ2 tests. We used multiple logistic regression to model the association between beta agonist use and SCD.
Results: 376 SCD cases and 365 controls met criteria and differed by age (69 vs. 65 y; p<0.0001) but not by gender (Males 60.4% vs. 63.6%, p=0.37). Prevalence of beta agonist use was significantly higher in cases vs. controls (25% vs. 12%, p<0.001). After adjusting for age, gender and body mass index, risk of SCD was significantly higher with beta agonist use (OR 2.9, 95% CI 1.9 – 4.4). The mean corrected QT interval (QTc) pooled across case status was significantly greater in beta agonist users vs. non-users (446±41 ms vs. 438±40 ms, p=0.03). When stratified by case status, mean QTc was prolonged in cases regardless of beta-agonist use (449±44 ms with use and 451±44 ms without use), while the shortest QTc was in controls that were non-users (427±32 ms, p<0.04). When stratified by case status as well as beta blocker use, risk of SCD due to beta agonist use was attenuated by beta blockers (prevalence of lone beta agonist use significantly higher in cases vs. controls; 31 vs. 7%, p<0.001).
Conclusions: Beta-agonists triple the risk of SCD in the community among patients with coronary artery disease and beta-blockers appear to diminish this risk. QTc prolongation, likely from direct effects on myocardial repolarizing ion channels as well as potassium depletion, is a potential mechanism.