Abstract Body (Do not enter title and authors here): Background: Compared to ambulatory patients with HF, patients hospitalized with HF may be more susceptible to the hemodynamic effects of SGLT2i initiation, which may be more pronounced in those with lower baseline blood pressure (BP). We examined changes in BP and the occurrence of symptomatic hypotension with in-hospital initiation of dapagliflozin.
Methods: DAPA ACT HF-TIMI 68 was a double-blind, placebo-controlled trial that randomized patients hospitalized with HF to dapagliflozin vs. placebo (primary results to be presented at ESC Congress 2025). The primary endpoint was CV death or worsening HF, with the occurrence of symptomatic hypotension leading to hospitalization or study drug discontinuation being a prespecified key safety outcome. Systolic BP (SBP) was collected at each study visit. Analyses were conducted using the safety set, including all patients receiving ≥1 dose of study drug.
Results: Of 2,389 patients,1,210 and 1,179 were randomized to dapagliflozin and placebo, with similar SBPs at randomization (119 [IQR 108-132] vs. 119 [108-133] mmHg respectively; p=0.61). SBPs were lower at 7 days (LS mean difference: -2.2 [95% CI -3.6, -0.8] mmHg) and 30 days (-2.1 [-3.6, -0.7] mmHg) but not at 60 days (-0.3 [-1.8, +1.2]) in patients assigned to dapagliflozin vs. placebo (Fig A). The occurrence of symptomatic hypotension was low, occurring in 3.6% and 2.2% of patients randomized to dapagliflozin vs. placebo (HR 1.62 [95% CI 0.996, 2.64]; p=0.052) most commonly within the first month from randomization (median 19 [IQR 6-32] days). The probability of symptomatic hypotension was greater in those with lower baseline SBP (p-trend < 0.001) irrespective of randomization to dapagliflozin or placebo (p-interaction = 0.96) (Fig B). Symptomatic hypotension seemed more apparent in those with newly diagnosed HF vs. chronic worsening HF (HRs 2.65 [95% CI 1.04, 6.72] vs. 1.30 [95% CI 0.73, 2.33] respectively). Efficacy outcomes by baseline SBP are embargoed pending presentation of the primary trial results.
Conclusion: In-hospital initiation of dapagliflozin in patients presenting with HF modestly lowered SBP within the first month of randomization. There was a trend towards more symptomatic hypotension with dapagliflozin, but the rates were low overall. Symptomatic hypotension was more common in those with lower baseline SBP, but irrespective of treatment. Patients with new onset HF, in whom multiple other drugs may be being initiated, may be more susceptible.