Renin–Angiotensin–Aldosterone System Optimization for Acute Decompensated Heart Failure Patients (ROAD-HF): Rationale and Design
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The long-term benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with chronic congestive heart failure are well-known, making them one of the most widely prescribed medications. However, the administration of ACEIs/ARBs in acute decompensated heart failure (ADHF) can increase the risk of morbidity and mortality secondary to worsening renal function (WRF). A decrease in estimated glomerular filtration rate (eGFR) during the treatment of ADHF has been associated with an increase in mortality proportional to the degree of WRF.
The aim of our study is to determine whether withholding ACEIs/ARBs during the initial 72 h of admission in patients with ADHF will prevent WRF and allow more effective diuresis.
Four hundred and thirty patients will be randomized to the intervention (withholding ACEIs/ARBs) or control (continue/start ACEIs/ARBs) arms for 72 h. Primary outcomes include rates of acute kidney injury (AKI), patient global assessment, and change in kinetic eGFR over 72 h, while secondary outcomes include change in weight, fluid balance, change in signs and symptoms of congestion, change in renal function, change in urinary biomarkers (tissue inhibitor of metalloproteinases 2 [TIMP-2] × insulin-like growth factor-binding protein 7 [IGFBP7]), patients experiencing treatment failure, hospital length of stay (LOS), cost analysis, mortality within 30 days, and hospital readmissions over 30 days and 1 year.
This prospective clinical trial will prove if withholding ACEIs/ARBs will prevent AKI in ADHF. It will help us understand the complex interactions between the heart and kidney, and delineate the best treatment strategy for ADHF. Holding ACEIs/ARBs might help preserve renal function, and decrease hospital LOS, readmission rates, and cost of care in ADHF.
ClinicalTrials.gov identifier: NCT03695120.
BD designed the study; BD, MD, GS, and RM undertook the literature review, wrote the manuscript and contributed equally to this manuscript; CS, JG, ABh, NR, and ABa undertook critical revision; and SB helped with the statistical analysis and reviewed the manuscript. All authors read and approved the final version submitted for publication.
Compliance with Ethical Standards
This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
Bhagwan Dass, Michelle Dimza, Girish Singhania, Cody Schwartz, Jerin George, Avni Bhatt, Nila Radhakrishnan, Asha Bansari, Shahab Bozorgmehri, and Rajesh Mohandas declare no potential conflicts of interest that may be relevant to this work.
This study has been approved by the University of Florida Institutional Review Board (IRB) and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in this study.
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