AIMS: Empagliflozin improves outcomes in acute heart failure (AHF). Patients with AHF and low blood pressure (BP) have poor prognosis. Whether empagliflozin is effective and safe in patients with AHF and low BP is currently unknown. The aim of this study was to assess the efficacy and safety of empagliflozin (vs. placebo) in patients with low BP - either systolic BP (SBP) <
110 mmHg or diastolic BP (DBP) <
70 mmHg - at randomization. METHODS AND RESULTS: EMPULSE included 530 patients with AHF followed for 90 days. The primary outcome was a hierarchical composite of all-cause mortality, HF events, and Kansas City Cardiomyopathy Questionnaire total symptom score changes at 90 days tested using the win ratio (WR). Patients were required to have SBP ≥100 mmHg for randomization. A total of 131 (25%) patients had SBP <
110 mmHg and 190 (36%) DBP <
70 mmHg. In placebo, low BP was associated with more clinical and adverse events. Compared to placebo, BP changes with empagliflozin were of small magnitude (-2 to 2 mmHg), not reaching statistical significance. Patients presenting with low BP increased their BP, on average, throughout the 90-day follow-up, regardless of treatment group. Empagliflozin (vs. placebo) improved clinical outcomes regardless of BP at randomization, potentially with a larger magnitude of effect in patients presenting with low DBP at randomization: primary outcome WR = 1.48, 95% confidence interval (CI) 1.15-1.90, p = 0.0025
WR = 1.23, 95% CI 0.94-1.60 in DBP ≥70 mmHg and WR = 2.11, 95% CI 1.46-3.04 in DBP <
70 mmHg (interaction p = 0.02). CONCLUSIONS: Patients admitted for AHF with low BP had a higher risk of clinical events. Empagliflozin did not lower BP more than placebo and was effective and safe irrespective of BP. Empagliflozin should be considered for the treatment of AHF patients even when presenting with low BP.