Outcomes/Effectiveness Research

Variants in certain receptor genes affect the survival of patients with acute coronary syndrome who are prescribed beta-blocker therapy

Beta-blockers (beta-adrenergic antagonists) are typically prescribed to reduce the risk of further cardiac problems in patients discharged from the hospital after treatment for acute coronary syndrome (ACS, unstable angina or heart attack). However, specific sequence variants in the beta-adrenergic receptor genes can increase the mortality risk of patients with ACS discharged with beta-blocker therapy, according to a study supported in part by the Agency for Healthcare Research and Quality (HS11282).

Previous studies have shown an association between the beta1- and beta2-adrenergic receptors (ADRB1 and ADRB2) and response to beta-adrenergic blocker therapy. This study went further, finding that 39 percent of ACS patients with the ADRB2 79 CG genotype discharged with beta-blockers and 16 percent of those with ADRB2 46 GA genotype were at high risk for dying within 3 years after hospitalization for ACS.

These patients may need additional treatments to optimize their prognosis, suggest the researchers. They prospectively studied 735 patients admitted for ACS at two Kansas City medical centers in 2001 and 2002. They evaluated the effect of ADRB1, Arg389Gly (1165 CG), and Ser49Gly (145 AG) as well as ADRB2 Gly16Arg (46 GA), and Gln27Glu (79 CG) genotypes on 3-year survival of the 597 patients discharged with beta-blockers.

There was a significant association between ADRB2 genotypes and 3-year mortality among this patient group. For the 79 ADRB2 CG DNA sequence, 3-year mortality rates were 16 percent, 11 percent, and 6 percent for the CC, CG, and GG genotypes, respectively. For the ADRB2 46 GA DNA sequence, 3-year mortality estimates were 10 percent, 10 percent, and 20 percent for the GG, GA, and AA genotypes. The researchers found no mortality difference between genotypes among patients with ACS who were not discharged with beta-blocker therapy for either the 79 CG or 46 GA gene sequences. They indicate that more studies are needed to definitively demonstrate the potential benefit or harm of beta-blocker therapy within specific ADRB2 genotype groups.

See "B2-adrenergic receptor genotype and survival among patients receiving B-blocker therapy after an acute coronary syndrome," by David E. Lanfear, M.D., Philip G. Jones, M.S., Sharon Marsh, Ph.D., and others, in the September 28, 2005, Journal of the American Medical Association 294(12), pp. 1526-1533.

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