Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
CPT Pharmacometrics Syst Pharmacol. 2021 Sep;10(9):1081-1091. doi: 10.1002/psp4.12676. Epub 2021 Jul 16.
To characterize and compare various medicines for chronic heart failure (CHF), changes in circulatory physiological parameter during pharmacotherapy were investigated by a model-based meta-analysis (MBMA) of circulatory physiology. The clinical data from 61 studies mostly in patients with heart failure with reduced ejection fraction (HFrEF), reporting changes in heart rate, blood pressure, or ventricular volumes after treatment with carvedilol, metoprolol, bisoprolol, bucindolol, enalapril, aliskiren, or felodipine, were analyzed. Seven cardiac and vasculature function indices were estimated without invasive measurements using models based on appropriate assumptions, and their correlations with the mortality were assessed. Estimated myocardial oxygen consumption, a cardiac load index, correlated excellently with the mortality at 3, 6, and 12 months after treatment initiation, and it explained differences in mortality across the different medications. The analysis based on the present models were reasonably consistent with the hypothesis that the treatment of HFrEF with various medications is due to effectively reducing the cardiac load. Assessment of circulatory physiological parameters by using MBMA would be insightful for quantitative understanding of CHF treatment.
为了描述和比较慢性心力衰竭（CHF）的各种药物，通过循环生理模型的荟萃分析（MBMA）研究了药物治疗期间循环生理参数的变化。对 61 项研究的临床数据进行了分析，这些研究主要针对射血分数降低的心力衰竭（HFrEF）患者，报告了在服用卡维地洛、美托洛尔、比索洛尔、布新洛尔、依那普利、阿利克仑或非洛地平治疗后心率、血压或心室容积的变化。使用基于适当假设的模型，无需进行侵入性测量即可估算七个心脏和血管功能指数，并评估其与死亡率的相关性。估计的心肌耗氧量是一个心脏负荷指数，与治疗后 3、6 和 12 个月的死亡率密切相关，它解释了不同药物之间死亡率的差异。基于目前模型的分析与假设基本一致，即使用各种药物治疗 HFrEF 是由于有效地降低了心脏负荷。通过使用 MBMA 评估循环生理参数，可以深入了解 CHF 的治疗。
