CYP2D6 Genetic Variation and Beta-Blocker Maintenance Dose in Patients with Heart Failure

Pharm Res. 2017 Aug;34(8):1615-1625. doi: 10.1007/s11095-017-2104-8. Epub 2017 Feb 8.


Purpose: This study examined whether a CYP2D6 polymorphism (CYP2D6*4) was related to beta-blocker maintenance dose in patients with heart failure.

Methods: Logistic regression modeling was utilized in a retrospective chart-review analysis of heart-failure patients (60% Male, 90% of European descent) to assess whether CYP2D6*4 (non-functional CYP2D6 allele present in 1 of 5 individuals of European descent) is associated with maintenance dose of carvedilol (n = 65) or metoprolol (n = 33).

Results: CYP2D6*4 was associated with lower maintenance dose of metoprolol (OR 0.13 [95% CI 0.02-0.75] p = 0.023), and a trend was observed between CYP2D6*4 and higher maintenance dose of carvedilol (OR 2.94 [95% CI 0.84-10.30] p = 0.093). None of the patients that carried CYP2D6*4 achieved the recommended target dose of metoprolol (200 mg/day).

Conclusion: Consistent with the role of CYP2D6 in the metabolism of metoprolol, the tolerated maintenance dose of metoprolol was lower in CYP2D6*4 carriers compared to non-carriers. Consistent with the role of CYP2D6 in activation of carvedilol, tolerated maintenance dose of carvedilol was higher in CYP2D6*4 carriers compared to non-carriers. Further investigation is warranted to ascertain the potential of CYP2D6 as a potential predictive biomarker of beta-blocker maintenance dose in heart failure patients.

Keywords: CYP2D6; beta-blocker dose; carvedilol; heart failure; metoprolol; pharmacogenetics.

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adult
  • Aged
  • Aged, 80 and over
  • Carbazoles / administration & dosage
  • Carvedilol
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Heart Failure / drug therapy*
  • Heart Failure / genetics
  • Heart Failure / metabolism
  • Humans
  • Male
  • Metoprolol / administration & dosage
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic
  • Propanolamines / administration & dosage
  • Retrospective Studies


  • Adrenergic beta-Antagonists
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • Cytochrome P-450 CYP2D6
  • Metoprolol