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Pharmacogenomics J. 2017 Mar;17(2):192-200. doi: 10.1038/tpj.2016.4. Epub 2016 Mar 1.

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

Author information

1
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
2
Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
3
Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
4
Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
5
Washington University School of Medicine, St Louis, MO, USA.
6
Tufts Medical Center, Boston, MA, USA.
7
University of Pennsylvania, Philadelphia, PA, USA.
8
Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
9
National Heart, Lung, and Blood Institute, Bethesda, MD, USA.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00577135 NCT00608491 NCT01132846.

PMID:
26927285
PMCID:
PMC5009007
[Available on 2017-09-01]
DOI:
10.1038/tpj.2016.4
[Indexed for MEDLINE]
Free PMC Article

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