Dapagliflozin in Acute Cardiovascular Conditions

Figures

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  Figure 1. Win Ratio Flowchart for the Primary Outcome According to Reason for Intensive Care Unit Admission Distribution of wins, ties, and losses for the dapagliflozin group in paired comparisons, stratified by each level of the hierarchical primary composite outcome. (A) Shows patients admitted for acute cardiovascular reasons; (B) shows those admitted for other reasons. Early ties were assigned when both members of a pair died during hospitalization. Percentages reflect the proportion at each hierarchy level. The win ratio (dapagliflozin wins ÷ losses) was 0.94 (2,744/2,924; 95% CI: 0.77-1.15) for the cardiovascular subgroup and 1.05 (12,604/12,050; 95% CI: 0.91-1.21) for the noncardiovascular subgroup. The interaction P value comparing treatment effects between subgroups was 0.69. ICU = intensive care unit; KRT = kidney replacement therapy.

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  Figure 2. Dapagliflozin Effects on Urinary Output, Fluid Balance, and Vasoactive Support During Study Days 1 to 5 (A-D) Show treatment effects over 5 days with 95% credible intervals (red shaded areas). Percentages for each study day indicate probability of higher urinary output, negative fluid balance, and higher vasoactive requirements. (A) Urinary output difference (dapagliflozin minus control) in mL/day. (B) Fluid balance difference (dapagliflozin minus control) in mL/day. (C) Expected norepinephrine dose difference (dapagliflozin minus control) in μg/kg/min representing the combined effect of both the probability of use and dose intensity among recipients. (D) Expected dobutamine dose difference (dapagliflozin minus control) in μg/kg/min. All models were adjusted for age and baseline inotropic support, mechanical ventilation, and vasopressor use. Bayesian hierarchical models incorporated patient-level random effects to account for repeated measures. The dashed horizontal line at zero represents no treatment effect.

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  Central Illustration. Overview of the DEFENDER Trial Subgroup Analysis Examining Dapagliflozin Effects According to the Reason for Intensive Care Unit Admission The trial randomized 507 critically ill participants with acute organ dysfunction to dapagliflozin (n = 248) or control (n = 259). Participants were stratified by cardiovascular (CV) vs noncardiovascular (non-CV) reasons for ICU admission. Two primary analyses were conducted: 1) Assessment of efficacy and safety outcomes comparing treatment effects between CV and non-CV subgroups, which showed no heterogeneity of treatment effect (interaction P = 0.69 for primary outcome) and no increase in adverse events and 2) evaluation of daily ICU and laboratory parameters over 5 days in 134 CV patients with available data, revealing that dapagliflozin likely increased urinary output (212 mL/day [95% CrI: 30-392]), with minimal increases in norepinephrine (0.01 μg/kg/min [95% CrI: −0.01 to 0.04]) and dobutamine (0.43 μg/kg/min [95% CrI: −0.33 to 1.28]) requirements. CrI = credible interval; DEFENDER = Dapagliflozin in Critically Ill Patients with Acute Organ Dysfunction; ICU = intensive care unit.