Abstract 13725: The Dose Difference of Carvedilol for Heart Failure Management Between Asian-Americans and Japanese Could Show No Difference in the Improvement of Heart Function

Abstract

Introduction: Carvedilol has improved cardiac mortality and morbidity for heart failure with reduced ejection fraction (HFrEF). The initial and target doses used in the Japanese randomized controlled trials (RCTs) were almost half of those in the USA leading to markedly lower recommended doses for HF management the in Japanese national guidelines compared to the USA. Hypothesis: Race may play a role in the optimal dose of carvedilol for HFrEF management. Methods: The international collaborative study was performed to compare the dose difference and the effect on heart functions, such as left ventricular EF (LVEF) and heart rate (HR), among Asian-Americans (AA), Caucasians (CA), and Japanese (JA) using real-world data. Each local ethics committee approved the study protocol at the University of California, San Diego (UCSD), the Osaka University Hospital (OUH), and the OU pharmaceutical sciences. The initial population at UCSD Health and OUH consisted of 1078 patients with HFrEF (≥ 20 years, EF<40%) treated with carvedilol (668 AA and CA and 410 JA). After inclusion/exclusion criteria, the study population consisted of 26 AA, 36 CA, and 96 JA. Results: Initial carvedilol dose (mg/day) (AA, 14.5 ± 11.9; CA, 19.1 ± 18.7; JA, 4.3 ± 4.2) and the dose at one year (30.9 ± 22.4; 34.5 ± 21.4; 11.2 ± 6.5) were significantly lower for JA compared to AA or CA ( p < 0.05 vs JA, respectively). AA had the highest frequency of carvedilol discontinuation (%; AA, 10.7; CA, 2.6; JA, 6.5) and dose reduction (18.4, 10.7, 2.2) ( p < 0.05, chi-square test). Clinical measurements of LVEF (%) measured before carvedilol initiation and after one year (before; 28.9 ± 8.8, 26.5 ± 8.0, 28.8 ± 7.4, after; 42.9 ± 11.1, 37.5 ± 15.3, 41.2 ± 13.1) and HR (beats/min) (before; 81.9 ± 19.0, 77.7 ± 13.5, 74.7 ± 10.9, after; 77.8 ± 10.6, 74.0 ± 12.5, 69.4 ± 9.4) showed no significant difference among the three groups. There were also no significant differences in event-free survival and in changes from baseline to 1 year in LVEF and HR, LVDd, or LVDs. Conclusions: JA patients exhibited similar effectiveness compared to AA and CA despite markedly lower carvedilol doses. Doses in AA were more similar to CA vs JA. Dose-deescalation may be an option in Asian HFrEF patients intolerable to high doses of carvedilol.