Predictors of therapeutic response to beta-blockers in patients with heart failure in Taiwan.
OBJECTIVE
Chinese are more sensitive to beta-blockers than Caucasians. However, data regarding beta-blocker therapy in heart failure (HF) patients in Taiwan are lacking. We aimed to evaluate the improvement of left ventricular function and the potential predictors of response to beta-blocker therapy in Taiwanese HF patients.


METHODS
We enrolled 34 HF patients with baseline left ventricular ejection fraction (LVEF) </= 40%. Beta-blockers were titrated up to the maximum tolerable dose. LVEF prior to beta-blocker usage and at the stable dose were obtained. We also sequenced the entire gene encoding beta1-adrenoceptor to assess the relationships between LVEF improvement and gene polymorphisms.


RESULTS
Beta-blocker therapy (25 +/- 22 months) with a mean stable dose of 12 +/- 8 mg carvedilol/day significantly improved LVEF (from 28 +/- 8% to 40 +/- 15%, p < 0.001). Stepwise multiple linear regression analysis identified dilated cardiomyopathy (beta = 18.32, p = 0.0004), baseline LVEF (beta = -0.85, p = 0.0020), use of amiodarone (beta = -22.58, p = 0.0034) and square of digoxin dose (beta = -314.25, p = 0.0059) at stable beta-blocker dose as independent predictors of LVEF improvement, where beta is the estimated regression coefficient. We did not find any novel variant of beta1-adrenoceptor gene other than those previously reported at codons 49 and 389, with the allele distributions similar to those found in Caucasians, and these polymorphisms did not imply therapeutic response to beta-blocker.


CONCLUSIONS
We demonstrated the therapeutic effects of beta-blockers in Taiwanese HF patients with a dose lower than what has been reported in Western people. Moreover, patients with the etiology of dilated cardiomyopathy or lower baseline LVEF predicted a greater LVEF improvement. The beta1-adrenoceptor gene polymorphisms were not responsible for the difference in sensitivity to beta-blockers in this Taiwanese population.
Hu
Hsin
H
Graduate Institute of Clinical Pharmacy, National Taiwan University College of Medicine, Taipei, Taiwan.
Jui
Hsiang-Yiang
HY
Hu
Fu-Chang
FC
Chen
Yen-Hui
YH
Lai
Ling-Ping
LP
Lee
Chii-Ming
CM
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D044466:Asian People; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D013624:Taiwan; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1