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

Abstract

Background: One of the major indications for digoxin use is the treatment of heart failure [HF]. Although 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 outcomes 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”, “hospitalization 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. Treatment 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 subset of patients. Conclusion: The results of this meta-analysis suggest that digoxin does not have any significant effect on long-term outcomes of HFpEF patients, including “all-cause mortality”, “all-cause hospitalization”, “hospitalization because of HF” and “all-cause mortality or hospitalization of HF”.