A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: A meta-analysis of three clinical trials

S. De Denus, J. L. Rouleau, D. L. Mann, G. S. Huggins, T. P. Cappola, S. H. Shah, J. Keleti, Y. F. Zada, S. Provost, A. Bardhadi, M. S. Phillips, V. Normand, I. Mongrain, M. P. Dubé

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Abstract

We conducted a meta-analysis of pharmacogenomic substudies of three randomized trials conducted in patients with decompensated heart failure (HF) that were led by National Heart Lung and Blood Institute (NHLBI)-funded HF Network to test the hypothesis that candidate genes modulate net fluid loss and weight change in patients with decompensated HF treated with a furosemide-based diuretic regimen. Although none of the genetic variants previously shown to modulate the effects of loop diuretics in healthy individuals were associated with net fluid loss after 72 h of treatment, a set of rare variants in the APOL1 gene, which codes for apolipoprotein L1 (P=0.0005 in the random effects model), was associated with this end point. Moreover, a common variant in the multidrug resistance protein-4 coding gene (ABCC4, rs17268282) was associated with weight loss with furosemide use (P=0.0001). Our results suggest that both common and rare genetic variants modulate the response to a furosemide-based diuretic regimen in patients with decompensated HF.

Original languageEnglish
Pages (from-to)192-200
Number of pages9
JournalPharmacogenomics Journal
Volume17
Issue number2
DOIs
StatePublished - Mar 1 2017

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    De Denus, S., Rouleau, J. L., Mann, D. L., Huggins, G. S., Cappola, T. P., Shah, S. H., Keleti, J., Zada, Y. F., Provost, S., Bardhadi, A., Phillips, M. S., Normand, V., Mongrain, I., & Dubé, M. P. (2017). A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: A meta-analysis of three clinical trials. Pharmacogenomics Journal, 17(2), 192-200. https://doi.org/10.1038/tpj.2016.4