PDF(Pubmed)
Abstract：
The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181-0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [-5.49-4.12]; LVDd, -0.55 [-3.24-2.15]; LVDd index, -0.25 [-1.92-1.43]; LVDs, -0.03 [-3.84-3.90]; LVDs index, -0.04 [-2.38-2.30]; heart rate, 1.62 [-3.07-6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.
摘要：
与美国指南相比，日本国家指南建议使用卡维地洛治疗心力衰竭并降低射血分数（HFrEF）。使用真实世界的数据，我们确定日本患者（JPNs）的卡维地洛初始剂量和目标剂量是否与美国患者（USPs）不同，尤其是亚裔美国人（ASA）和高加索人（CA），并调查了结果的差异。我们从电子病历中收集数据,包括人口统计，卡维地洛剂量，耐受性,心脏功能指标，如EF，心血管事件包括全因死亡,和加州大学的实验室值，圣地亚哥健康和大阪大学。JPNs的卡维地洛起始剂量（mg/天）显着降低（66USP由38CA和28ASA组成，17.1±16.2；93JPN，4.3±4.2，p<0.001）和开始后一年（33.0±21.8；11.2±6.5，p<0.001），与USP相比，剂量中止和减少的相对比率（RR）显着降低（RR：0.406，95％置信区间（CI）：0.181-0.911，p<0.05）。CAs显示最高的降低率(0.184)，ASAs的停药率最高(0.107)。在两个区域之间，从每个心脏功能指标的基线变化（LVEF，-0.68[-5.49-4.12];LVDd,-0.55[-3.24-2.15]；LVDd指数，-0.25[-1.92-1.43];LVDs,-0.03[-3.84-3.90]；LVDs指数，-0.04[-2.38-2.30];心率,1.62[-3.07-6.32])。无事件生存率在种族之间没有差异（p=0.172）。最后，尽管JPN表现出卡维地洛剂量明显较低，它们的剂量有效性有可能不劣于USP。剂量降低,不停止,在某些亚洲和ASAHFrEF患者中，可能是一种选择，无法耐受高剂量卡维地洛。
