CHF patients homozygous for the Gln27 polymorphism had a significantly lower rate of good clinical response to carvedilol compared to those with the Glu27 polymorphism (26% vs 63%, P=0.003).
Observational (n=80)
Does beta2-adrenoceptor genotype influence the left ventricular functional response to carvedilol in patients with congestive heart failure?
The beta2-adrenoceptor genotype significantly influences the left ventricular functional response to carvedilol in patients with congestive heart failure, suggesting a potential role for genetic tailoring of beta-blocker therapy.
Absolute Event Rate: 26% vs 63%
p-value: p=0.003
Although the widespread introduction of beta-adrenoceptor antagonists into the management of congestive heart failure (CHF) has led to significant improvements in morbidity and mortality, it is also apparent that clinical responses to this therapy vary substantially. With the recognition that functionally significant genetic polymorphisms of the beta2-adrenoceptor exist with clinically relevant allelic frequency, we hypothesized that beta2-adrenoceptor genotype may affect the response to carvedilol. The clinical response, influence on left ventricular function and beta2-adrenoceptor (beta2AR) genotype was determined in 80 patients treated with carvedilol. A clinically significant improvement in left ventricular function (good responder) was defined as an absolute improvement of 10% in the left ventricular ejection fraction or 5% in the fractional shortening. Consistent with studies performed in vitro on the influence of beta2AR genotype and receptor desensitization, subjects who were homozygous for the allele encoding the Gln27 polymorphism displayed a significantly lower proportion of good responders than patients who were homozygous or heterozygous for the Glu27 polymorphism (26% versus 63%, P=0.003). These data demonstrate a significant influence of beta2AR genotype in the response to carvedilol in CHF patients. Accordingly, determination of beta2AR status may be of value in the tailoring of individual therapy in patients with CHF.
Kaye et al. (Sun,) conducted a observational in Congestive heart failure (n=80). Homozygous for Gln27 polymorphism vs. Homozygous or heterozygous for Glu27 polymorphism was evaluated on Clinically significant improvement in left ventricular function (absolute improvement of 10% in LVEF or 5% in fractional shortening) (p=0.003). CHF patients homozygous for the Gln27 polymorphism had a significantly lower rate of good clinical response to carvedilol compared to those with the Glu27 polymorphism (26% vs 63%, P=0.003).