A prospective study of the impact of AGTR1 A1166C on the effects of candesartan in patients with heart failure

Pharmacogenomics. 2018 May;19(7):599-612. doi: 10.2217/pgs-2018-0004. Epub 2018 Apr 27.

Abstract

Aim: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure.

Materials & methods: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%.

Results: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p = 0.022).

Conclusion: AGTR1 1166C carriers may experience a greater long-term compensatory renin-angiotensin-aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation. Clinicaltrials.gov : NCT00400582.

Keywords: biomarkers; cardiovascular diseases; pharmacodynamics; pharmacogenomics.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / pharmacokinetics
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Benzimidazoles / pharmacokinetics
  • Benzimidazoles / therapeutic use*
  • Biomarkers / blood
  • Biphenyl Compounds
  • Blood Pressure / drug effects
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / genetics
  • Humans
  • Kidney Function Tests
  • Male
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Receptor, Angiotensin, Type 1 / genetics*
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / genetics
  • Tetrazoles / pharmacokinetics
  • Tetrazoles / therapeutic use*
  • Treatment Outcome

Substances

  • AGTR1 protein, human
  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Biomarkers
  • Biphenyl Compounds
  • Peptide Fragments
  • Receptor, Angiotensin, Type 1
  • Tetrazoles
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • candesartan

Associated data

  • ClinicalTrials.gov/NCT00400582