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

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


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.

Publication types

  • Meta-Analysis

MeSH terms

  • Administration, Intravenous
  • Aged
  • Aged, 80 and over
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Clinical Trials as Topic
  • Female
  • Fluid Shifts / drug effects
  • Furosemide / administration & dosage*
  • Genotype
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / genetics
  • Heart Failure / physiopathology
  • Humans
  • Lipoproteins, HDL / genetics*
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics*
  • Pharmacogenetics
  • Pharmacogenomic Variants*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Sodium Potassium Chloride Symporter Inhibitors / administration & dosage*
  • Time Factors
  • Treatment Outcome
  • Water-Electrolyte Balance / drug effects


  • ABCC4 protein, human
  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Lipoproteins, HDL
  • Multidrug Resistance-Associated Proteins
  • Sodium Potassium Chloride Symporter Inhibitors
  • Furosemide

Associated data

  • ClinicalTrials.gov/NCT00577135
  • ClinicalTrials.gov/NCT00608491
  • ClinicalTrials.gov/NCT01132846