Digoxin and Outcomes in Patients with Heart Failure and Preserved Ejection Fraction (HFpEF) Patients: A Systematic Review and Meta- Analysis

Background: One of the major indications for digoxin use is the treatment of heart fail- ure (HF). Although the clinical application of digoxin in long-term outcomes in patients with HF and reduced ejection fraction (HFrEF) patients is well explained, the association between digoxin therapy and outcomes in patients with HF and preserved ejection fraction (HFpEF) is not very clear. Objectives: The aim of this study was to show the clinical efficacy of digoxin on long-term out- comes in subjects with HFpEF.Methods: PubMed, Embase, Scopus and Web of Science (ISI) electronic databases were searched until May 2021 to obtain relevant studies. The primary outcome was all-cause mortality attributed to treatment with digoxin. The secondary outcomes were “all-cause hospitalization”, “hospitaliza- tion because of HF” and “all-cause mortality or hospitalization of HF”. Results: Seven studies with more than 23000 patients with HFpEF, of which more than 4900 were treated with digoxin, fulfilled the eligibility criteria and were included in this meta-analysis. Treat- ment with digoxin was associated with a neutral effect on all-cause mortality (HR 1.04, 95% CI 0.91-1.20, I2 = 57.9%), all-cause hospitalization (HR 0.97, 95% CI 0.88-1.07, I2 = 0.0%), HF- hospitalization (HR 0.96, 95% CI 0.90-1.02, I2 = 41.4%), and all-cause mortality or HF- hospitalization (HR 1.07, 95% CI 0.91-1.26, I2 = 81.2%). In subgroup meta-analyses based on ejection fraction (EF), treatment with digoxin did not significantly alter these outcomes in each sub- set of patients. Conclusion: The results of this meta-analysis suggest that digoxin does not have any significant ef- fect on long-term outcomes of HFpEF patients, including “all-cause mortality”, “all-cause hospitali- zation”, “hospitalization because of HF” and “all-cause mortality or hospitalization of HF”. Registration Number: The PROSPERO registration number is CRD42021214181.