Dapagliflozin in Acute Cardiovascular Conditions: Insights From the DEFENDER Trial

Sodium-glucose cotransporter-2 inhibitors improve clinical outcomes across various settings, but their use in critically ill patients hospitalized for acute cardiovascular conditions remains unexplored.

Secondary analysis aimed to: 1) determine whether treatment effects of dapagliflozin differ between critically ill patients admitted for cardiovascular vs noncardiovascular reasons; and 2) to investigate acute effects of in-hospital dapagliflozin initiation in patients with acute cardiovascular conditions.

This secondary analysis of the DEFENDER (Dapagliflozin in Critically Ill Patients with Acute Organ Dysfunction) trial, which randomized 507 critically ill patients to dapagliflozin 10 mg daily or standard care alone, compared cardiovascular (n = 162) vs noncardiovascular (n = 345) admissions. The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay through 28 days, analyzed by win ratio; median in-hospital follow-up was 9 days (Q1-Q3: 5-17 days). Daily parameters were analyzed in 134 cardiovascular patients using Bayesian mixed models.

The win ratio for the primary outcome was 0.94 (95% CI: 0.77-1.15) in the cardiovascular subgroup and 1.05 (95% CI: 0.91-1.21) in the noncardiovascular subgroup (interaction P = 0.69). Serious adverse events were similar between arms in both subgroups. In cardiovascular patients, dapagliflozin increased urine output by 212 mL/day (95% credible interval: 30-392) and decreased fluid balance by -237 mL/day (95% credible interval: -447 to -26) with minimal increases in norepinephrine (0.01 μg/kg/min) and dobutamine (0.43 μg/kg/min) requirements.

No treatment effect heterogeneity was observed based on intensive care unit admission reason. Dapagliflozin use in critically ill cardiovascular patients appeared safe, demonstrating a modest diuretic effect with minimal vasoactive support increases, warranting further investigation. (Dapagliflozin in Patients With Critical Illness [DEFENDER]; NCT05558098).