背景:本研究旨在利用随机分组的第一数据,在射血分数降低的心力衰竭(HFrEF)中开始使用强心苷洋地黄毒苷时,制定简单的给药评分,双盲DIGIT-HF试验。
结果:在DIGIT-HF中,在所有患者中,洋地黄毒苷的剂量为0.07mg,每天一次(o.d.)。对于分数推导,对317名随机接受洋地黄毒苷治疗的患者进行了分析。在这些患者中,在研究第6周预定的血清水平测定后,洋地黄毒苷的剂量保持不变或已减少至0.05mgo.d.(97%的患者),以达到预定范围(10.5-23.6nmol/l)的血清浓度。在逻辑回归分析中,性别,年龄,体重指数(BMI),和估计的肾小球滤过率(eGFR)与剂量减少的需要相关,因此,选择用于进一步发展给药评分。最佳切点来自ROC曲线分析。最后,女性性别,年龄≥75岁,eGFR<50ml/min/1.73m2和BMI<27kg/m2各自被分配一个点用于洋地黄毒苷给药评分。评分≥1表示需要减少剂量,敏感性/特异性为81.6%/49.7%,分别。准确性在验证数据集中得到证实,包括64名随机接受洋地黄毒苷治疗的患者,敏感性/特异性为87.5%/37.5%,分别。
结论:在HFrEF患者中,在女性受试者中,洋地黄毒苷的治疗应以0.05mgo.d.开始,eGFR<50ml/min/1.73m2,BMI<27kg/m2,或年龄≥75岁。在任何其他病人中,洋地黄毒苷可以安全地开始在0.07mgo.d.
BACKGROUND: The present study aimed to develop a simple dosing score when starting the cardiac glycoside
digitoxin in heart failure with reduced ejection fraction (HFrEF) employing first data from the randomized, double-blinded DIGIT-HF trial.
RESULTS: In DIGIT-HF,
digitoxin was started with a dose of 0.07 mg once daily (o.d.) in all patients. For score derivation, 317 patients were analyzed who had been randomized to
digitoxin. In these patients, after scheduled determination of serum levels at study week 6, the
digitoxin dose had remained unchanged or had been reduced to 0.05 mg o.d. (97% of patients) to achieve serum concentrations within a predefined range (10.5-23.6 nmol/l). In logistic regression analyses, sex, age, body mass index (BMI), and estimated glomerular filtration rate (eGFR) were associated with need for dose reduction and, therefore, selected for further developing the dosing score. Optimal cut-points were derived from ROC curve analyses. Finally, female sex, age ≥ 75 years, eGFR < 50 ml/min/1.73 m2, and BMI < 27 kg/m2 each were assigned one point for the digitoxin dosing score. A score of ≥ 1 indicated the need for dose reduction with sensitivity/specificity of 81.6%/49.7%, respectively. Accuracy was confirmed in a validation data set including 64 patients randomized to digitoxin yielding sensitivity/specificity of 87.5%/37.5%, respectively.
CONCLUSIONS: In patients with HFrEF, treatment with digitoxin should be started at 0.05 mg o.d. in subjects with either female sex, eGFR < 50 ml/min/1.73m2, BMI < 27 kg/m2, or age ≥ 75 years. In any other patient,
digitoxin may be safely started at 0.07 mg o.d.