Impact of Digoxin Utilization on Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis.

Continuous-flow left ventricular assist devices (CF-LVADs) improve quality of life and survival in patients with advanced heart failure but are frequently complicated by gastrointestinal bleeding (GIB). Reduced pulsatile flow may induce mucosal hypoxia, upregulating factors such as hypoxia-inducible factor (HIF)-1α and triggering neo-angiogenesis, leading to the development of gastrointestinal angiodysplasias (GIADs), a common cause of GIB. Digoxin inhibits HIF-1α and may prevent GIAD development, although its impact on the incidence of GIB remains uncertain. This meta-analysis (PROSPERO ID: CRD42024626222) evaluated the association between digoxin use and GIB occurrence (primary outcome) in patients with CF-LVADs. Research articles including adults with CF-LVADs, comparing digoxin users versus nonusers were included. Overall, four studies were included (n = 14,917; age 55 ± 13 years, 21% female) with 2,742 patients in the digoxin group and 12,175 in the no-digoxin group. Continuous-flow left ventricular assist device was axial (HeartMate II) in 78% of cases and centrifugal (HeartMate 3/HeartWare) in 22%. Digoxin use was associated with a nonsignificant lower risk of GIB (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.49-1.01). However, regarding GIAD-related GIB, digoxin was associated with a significantly lower risk (HR: 0.33; 95% CI: 0.13-0.82). Among 14,917 patients with CF-LVADs, digoxin use was associated with a trend toward a lower risk of GIB and a lower risk of GIAD-related GIB.