Key result
Excluding patients with systolic blood pressure <110 mmHg in the EMPEROR-Preserved trial risks under-representing high-risk individuals and obscuring hypotension and renal risks of empagliflozin.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The exclusion of patients with a systolic blood pressure (SBP) < 110 mmHg (n = 455) risks under-representing high-risk individuals with advanced HFpEF. Sodium glucose cotransporter 2 inhibitors such as empagliflozin induce osmotic diuresis and volume depletion; excluding low-SBP patients may obscure risks of hypotension, syncope, or renal failure in this subgroup. Future studies should include such patients as prespecified subgroups or use multivariable models to adjust for U/J-shaped SBP–outcome relationships, thereby enhancing the safety profile of empagliflozin.”
“Patients with systolic blood pressure (SBP) < 110 mmHg (n = 455) were excluded to reduce potential bias from the well-documented U- or J-shaped association between SBP and cardiovascular outcomes, which is largely attributable to reverse causation. As demonstrated in a prior post hoc analysis of EMPEROR-Preserved, the benefits of empagliflozin on cardiovascular death, hospitalization for heart failure, and renal outcomes were consistent across the SBP spectrum, including in patients with SBP < 110 mmHg. Importantly, low SBP was not associated with an excess risk of adverse events such as acute kidney injury, volume depletion, or symptomatic hypotension.”
This commentary highlights the need to include HFpEF patients with low systolic blood pressure in future studies to fully understand the safety profile and risks of empagliflozin in this subgroup.
This commentary refers to ‘Empagliflozin in resistant hypertension and heart failure with preserved ejection fraction: the EMPEROR-Preserved trial’, by M. Böhm et al., https://doi.org/10.1093/eurheartj/ehae938 and the discussion piece ‘Uniform benefits of empagliflozin across hypertension categories: a response’, by M. Tokcan et al., https://doi.org/10.1093/eurheartj/ehaf798. To the Editor, We read with great interest Böhm et al.’s EMPEROR-Preserved trial,1 which advances our understanding of empagliflozin in heart failure with preserved ejection fraction (HFpEF). While the trial represents a valuable contribution, we propose the following methodological considerations to refine clinical translation and guide future research. The exclusion of patients with a systolic blood pressure (SBP) < 110 mmHg (n = 455) risks under-representing high-risk individuals with advanced HFpEF.2 Sodium glucose cotransporter 2 inhibitors such as empagliflozin induce osmotic diuresis and volume depletion3; excluding low-SBP patients may obscure risks of hypotension, syncope, or renal failure in this subgroup. Future studies should include such patients as prespecified subgroups or use multivariable models to adjust for U/J-shaped SBP–outcome relationships,4 thereby enhancing the safety profile of empagliflozin.
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Sheikh et al. (2025) conducted a letter in Heart failure with preserved ejection fraction (HFpEF) and resistant hypertension. Empagliflozin was evaluated. Excluding patients with systolic blood pressure <110 mmHg in the EMPEROR-Preserved trial risks under-representing high-risk individuals and obscuring hypotension and renal risks of empagliflozin.
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