|
|
Gene Variants Associated With Increased Risk of Death Among Heart
Patients Treated With Beta-Blockers
CHICAGO - Patients with certain gene variants who were prescribed
beta-blocker drugs after acute coronary syndrome (ACS) had an increased
risk of death over the next three years, according to a study in the
September 28 issue of JAMA.
Beta-blockers are drugs that block the action of beta-adrenergic
substances such as adrenaline in the "sympathetic" portion of the
nervous system - relieving stress on the heart, slowing the heartbeat,
and reducing blood vessel contraction in the heart, brain, and
throughout the body, according to background information in the
article. Previous data support an association between variants of the
ADRB1 and ADRB2 genes and response to beta-blocker therapy, but no
relationship between these variants and the survival of patients
receiving beta-blocker therapy has been reported.
David E. Lanfear, M.D., formerly of Washington University School of
Medicine, St. Louis, and colleagues conducted a prospective cohort
study of 735 ACS patients admitted to two medical centers between March
2001 and October 2002. The ACS patients were diagnosed with either
myocardial infarction (heart attack) or unstable angina (an
accelerating pattern of chest pain that lasts longer and is less
responsive to medication than stable angina). Among those enrolled in
the study, 597 were discharged from the hospital with beta-blocker
therapy. DNA testing was conducted to find out if the patients carried
any of four common variants of the ADRB1 and ADRB2 genes (ADRB1 1165
CG, 145 AG; ADRB2 46 GA, 79 CG).
The researchers followed the study patients for three years after
discharge. There were 84 deaths during follow-up.
"There was a significant association between ADRB2 genotype and
three-year mortality among patients prescribed beta blocker therapy,"
the authors report.
"For the 79 CG polymorphism, . three-year mortality rates were 16
percent (35 deaths), 11 percent (27 deaths), and six percent (four
deaths) for the CC, CG, and GG genotypes, respectively," they write.
"For the ADRB2 46 GA polymorphism, three-year . mortality estimates
were ten percent (17 deaths), ten percent (28 deaths), and 20 percent
(20 deaths) for the GG, GA, and AA genotypes, respectively."
No increased mortality risk was observed in patients with the same
ADRB2 gene variants who were not prescribed beta-blockers. No
association of the ADRB1 variants with mortality was observed in either
the beta-blocker group, or in the patients who were not prescribed
beta-blockers.
The researchers believe this initial description of an association of
ADRB2 genotype with survival among patients receiving beta-blocker
therapy has potentially important implications.
"Among ACS patients discharged with beta-blocker therapy, we have
identified a genetic association with survival that can assist in the
risk stratification of patients," they write. "Specifically, the 79 CC
and 46 AA groups (39 percent and 16 percent, respectively, of our
population) are at high risk for long-term mortality and may need
additional treatments to optimize their prognosis."
"We strongly encourage further replication of our findings in distinct
patient cohorts so that the potential benefit or harm of beta-blocker
therapy within specific ADRB2 genotype groups can be definitively
demonstrated," the authors conclude. "With further validation,
pharmacogenetic targeting of beta-blocker therapy may be an opportunity
to further improve ACS care and outcomes."
(JAMA.2005; 294:1526-1533. Available to the media at www.jamamedia.org)
Editor's Note: Dr. Lanfear is now with Henry Ford Hospital, Detroit.
This work was supported in part by grants from the Agency for
Healthcare Research and Quality, the NIH Pharmacogenetics research
network, the Specialized Centers of Clinically Oriented Research
(SCCOR) program of the National Heart, Lung, and Blood Institute, and
by an HFSA Research Fellowship Grant.
|
|