期刊
AMERICAN JOURNAL OF MEDICINE
卷 133, 期 3, 页码 347-351出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.amjmed.2019.07.046
关键词
Cardiovascular mortality; Drug interaction; Heart failure; Ivabradine; Loop diuretics
BACKGROUND: Ivabradine, a heart rate-slowing drug used to treat heart failure and (in Europe) angina, had varying impacts upon cardiovascular events in its 3 large outcome trials. Food and Drug Administration (FDA) analyses may explain the reasons for the variability. METHODS: An FDA reviewer analyzed the raw data from the 3 trials using logistic regressions to assess interactions between ivabradine and other drugs and forest plots to display dose responses. RESULTS: Ivabradine in its SHIFT heart failure trial shows a significant interaction with loop diuretics with a beneficial impact upon cardiovascular deaths (odds ratio 0.61; 95% confidence interval, 0.42-0.87, P = .007). This favorable effect is supported by similar interactions in the other 2 trials (BEAUTIFUL, SIGNIFY) and by a dose response for loop diuretics interacting with ivabradine in the SHIFT and BEAUTIFUL trials. The interaction is not related to heart failure severity. CONCLUSION: Ivabradine used concomitantly with a loop diuretic has a beneficial impact upon cardiovascular death. (C) 2019 Elsevier Inc. All rights reserved.
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