Predictors of Therapeutic Response to Beta-blockers in Patients with Heart Failure in Taiwan

Abstract

Chinese are more sensitive to β-blockers than Caucasians. However, data regarding β-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 β-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 β-blocker usage and at the stable dose were obtained. We also sequenced the entire gene encoding β1-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 (β= 18.32, p = 0.0004), baseline LVEF (β=−0.85, p = 0.0020), use of amiodarone (β = −22.58, p = 0.0034) and square of digoxin dose (β=−314.25, p = 0.0059) at stable β-blocker dose as independent predictors of LVEF improvement, where β is the estimated regression coefficient. We did not find any novel variant of β1-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 β-blocker. Conclusion: We demonstrated the therapeutic effects of β-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 β1-adrenoceptor gene polymorphisms were not responsible for the difference in sensitivity to β-blockers in this Taiwanese population.

Keywords

• β-adrenergic blockers
• β1-adrenergic receptor
• genetic polymorphism
• heart failure
• treatment effectiveness