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

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de Denus, S; Rouleau, JL; Mann, DL; Huggins, GS; Cappola, TP; Shah, SH; Keleti, J; Zada, YF; Provost, S; Bardhadi, A; Phillips, MS; Normand, V ...
Published in: Pharmacogenomics J
March 2017

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.

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Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

March 2017

Volume

17

Issue

2

Start / End Page

192 / 200

Location

United States

Related Subject Headings

  • Water-Electrolyte Balance
  • Treatment Outcome
  • Time Factors
  • Sodium Potassium Chloride Symporter Inhibitors
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Pharmacology & Pharmacy
  • Pharmacogenomic Variants
  • Pharmacogenetics
  • Multidrug Resistance-Associated Proteins
 

Citation

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de Denus, S., Rouleau, J. L., Mann, D. L., Huggins, G. S., Cappola, T. P., Shah, S. H., … Dubé, M.-P. (2017). A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials. In Pharmacogenomics J (Vol. 17, pp. 192–200). United States. https://doi.org/10.1038/tpj.2016.4
Denus, S. de, J. L. Rouleau, D. L. Mann, G. S. Huggins, T. P. Cappola, S. H. Shah, J. Keleti, et al. “A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials.” In Pharmacogenomics J, 17:192–200, 2017. https://doi.org/10.1038/tpj.2016.4.
de Denus S, Rouleau JL, Mann DL, Huggins GS, Cappola TP, Shah SH, et al. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials. In: Pharmacogenomics J. 2017. p. 192–200.
de Denus, S., et al. “A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials.Pharmacogenomics J, vol. 17, no. 2, 2017, pp. 192–200. Pubmed, doi:10.1038/tpj.2016.4.
de Denus S, Rouleau JL, Mann DL, Huggins GS, Cappola TP, Shah SH, Keleti J, Zada YF, Provost S, Bardhadi A, Phillips MS, Normand V, Mongrain I, Dubé M-P. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials. Pharmacogenomics J. 2017. p. 192–200.

Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

March 2017

Volume

17

Issue

2

Start / End Page

192 / 200

Location

United States

Related Subject Headings

  • Water-Electrolyte Balance
  • Treatment Outcome
  • Time Factors
  • Sodium Potassium Chloride Symporter Inhibitors
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Pharmacology & Pharmacy
  • Pharmacogenomic Variants
  • Pharmacogenetics
  • Multidrug Resistance-Associated Proteins