Lack of association between adrenergic receptor genotypes and survival in heart failure patients treated with carvedilol or metoprolol.

Published

Journal Article

OBJECTIVES: This study investigated the role of adrenergic receptor genetics on transplant-free survival in heart failure (HF). BACKGROUND: Discordant results exist for genetic associations between adrenergic receptor alleles and end points of beta-blocker response in HF patients. METHODS: We identified 637 patients enrolled in 2 U.S. cardiovascular genetic registries with HF and left ventricular systolic dysfunction who were discharged on beta-blocker, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), and diuretic medications. End points were determined through the national Social Security Death Master File and transplant records. We genotyped 5 polymorphisms in 3 genes: ADRB1 (S49G, R389G), ADRB2 (G16R, Q27E), and ADRA2C (Del322-325) using 5' nuclease assays and performed a multivariable clinical-genetic analysis. RESULTS: A total of 190 events (29.8%) occurred over a median follow-up of 1,070 days. Multivariable analysis showed a significant effect of 4 clinical factors on survival: age (p = 0.006), gender (p = 0.005), ejection fraction (p = 0.0002), and hemoglobin (p = 0.00010). There was no significant effect of the polymorphisms or haplotypes analyzed on survival. CONCLUSIONS: Genotypes and haplotypes of ADRB1, ADRB2, and ADRA2C did not significantly affect survival in metoprolol-treated or carvedilol-treated HF patients in this study. These results complement the findings of 2 similarly designed previous studies, but do not replicate an association of ADRB2 haplotypes and survival. All 3 studies differ from a survival benefit reported for bucindolol-treated homozygous ADRB1 R389 individuals. This may be attributable to a drug-specific interaction between genotype and outcome with bucindolol that does not seem to occur with metoprolol or carvedilol.

Full Text

Duke Authors

Cited Authors

  • Sehnert, AJ; Daniels, SE; Elashoff, M; Wingrove, JA; Burrow, CR; Horne, B; Muhlestein, JB; Donahue, M; Liggett, SB; Anderson, JL; Kraus, WE

Published Date

  • August 19, 2008

Published In

Volume / Issue

  • 52 / 8

Start / End Page

  • 644 - 651

PubMed ID

  • 18702968

Pubmed Central ID

  • 18702968

Electronic International Standard Serial Number (EISSN)

  • 1558-3597

Digital Object Identifier (DOI)

  • 10.1016/j.jacc.2008.05.022

Language

  • eng

Conference Location

  • United States