Effects of neurohormonal antagonists on blood pressure in patients with heart failure with reduced ejection fraction (HFrEF): a systematic review protocol

BACKGROUND: Several cardiovascular pathologies cause heart failure. Heart failure with reduced ejection fraction (HFrEF) is deteriorated by neurohormonal activation, so neurohormonal antagonists are recommended in HFrEF patients. They improve morbidity, mortality, and quality of life and reduce hospital admissions. Heart failure treatment guidelines recommend achieving target doses of those drugs. However, many clinicians prescribe suboptimal doses for the fear of inducing hypotension. The aim of this systematic review and meta-analysis is to understand whether it is still beneficial to uptitrate the doses of those drugs even if the patient is at the risk of developing hypotension. METHODS: The primary outcome is symptomatic or asymptomatic hypotension in patients on neurohormonal antagonist drugs for HFrEF. Secondary outcomes are blood pressure reduction, New Yok Heart Association functional class deterioration, non-fatal cardiovascular events, cardiovascular mortality, all-cause mortality, heart failure hospitalizations, and adverse events. Randomized controlled trials involving adults with HFrEF will be included. Comprehensive literature search will be done in MEDLINE, Scopus, Web of Science, WHO Global Index Medicus, and the Cochrane Central Register of Controlled Trials. MEDLINE will be searched first using controlled vocabulary and free text terms and then adapted to other databases. Linear and nonlinear dose-response meta-analyses will be conducted. Publication bias and statistical heterogeneity will be tested by Egger’s regression and Cochran’s Q tests, respectively. Sensitivity, subgroup, and meta-regression analyses will be performed. Grading of Recommendations Assessment, Development and Evaluation approach will be used to judge the quality of evidence. DISCUSSION: This systematic review and meta-analysis will provide information about the risk of hypotension in patients on neurohormonal antagonist drugs for HFrEF. The results will be published in a peer-reviewed journal. The implications for further research will be discussed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019140307