Model‐based meta‐analysis of changes in circulatory system physiology in patients with chronic heart failure

• Published in: CPT: pharmacometrics and systems pharmacology Vol. 10; no. 9; pp. 1081 - 1091
• Main Authors: Takaoka, Ryota, Soejima, Yukako, Guro, Sayuri, Yoshioka, Hideki, Sato, Hiromi, Suzuki, Hiroshi, Hisaka, Akihiro
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2021; John Wiley and Sons Inc; Wiley
• Subjects: Angina pectoris; Blood pressure; Blood Pressure - drug effects; Cardiology; Cardiovascular Agents - administration & dosage; Cardiovascular Agents - pharmacology; Chronic Disease; Circulatory system; Clinical trials; Data collection; Diuretics; Drug therapy; Ejection fraction; Heart failure; Heart Failure - drug therapy; Heart Failure - mortality; Heart Failure - physiopathology; Heart rate; Heart Rate - drug effects; Humans; Load; Meta-analysis; Models, Biological; Mortality; Physiology; Randomized Controlled Trials as Topic; Stroke Volume - drug effects; Time Factors
• ISSN: 2163-8306; 2163-8306
• DOI: 10.1002/psp4.12676

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.