No interaction between SBP and effects of SGLT2i on outcomes in HFrEF

Empagliflozin improves cardiovascular and renal outcomes in heart failure irrespective of systolic blood pressure

Literature - Böhm M, Anker SD, Butler J et al. - J Am Coll Cardiol 2021; 78:1337-48,

Introduction and methods

Aim of the study

Studies have reported that SGLT2 inhibitors reduce systolic blood pressure (SBP) in patients with diabetes and hypertension [1,2]. Therefore, these heart failure medications are often not prescribed or are used at low doses in patients with a low SBP [3,4]. But HFrEF patients with the lowest SBP are at the highest risk of CV death and hospitalization for HF [5] and may not be likely to receive SGLT2i treatment. This analysis of the EMPEROR-Reduced trial examined the effect of baseline SBP on efficacy of empagliflozin in HFrEF patients with a focus on patients with the lowest SBP.

Study design

In the EMPEROR-Reduced trial , 3730 HFrEF patients with or without diabetes were randomized double-blind to receive placebo or empagliflozin in addition to standard therapy for heart failure. BP was measured at the screening visit and subsequent visits using a standard manometer at the same arm in a sitting position after 5 min of rest. The mean of 3 measurements was used.

For this analysis, patients were grouped according to baseline SBP: <110 mgHg, 110-130 mmHg and >130 mmHg.

Primary outcome

Primary outcome was the time to first event of the composite of adjudicated CV death or hospitalization for HF.

Main results

  • In patients with placebo, the incidence rate per 100 patient years for the primary endpoint was 16.5 in patients with SBP >130 mmHg to 20.8 in patients with SBP of 110-130 mmHg and 26.3 in patients with SBP<110 mmHg (Ptrend=0.0015). The event rate for total hospitalizations for HF increased from 17.9 in patients with SBP>130 mmHg to 22.0 in patients with SBP 110-130 mmHg to 28.1 in patients with SBP<110 mmHg (Ptrend=0.0075).
  • After correction for placebo, a slight increase in BP in the <100 mmHg group was seen, no change in the 110-130 mmHg group and a slight reduction in the >130 mmHg group, but between-group differences were not significant.
  • Treatment with empagliflozin did not increase the risk of hypotension or symptomatic hypotension.
  • The relative risk reduction of the primary outcome by empagliflozin was similar across all SBP groups. SBP also not influenced the magnitude of risk reduction by empagliflozin on total hospitalization for HF.
  • When treatment effects were examined using SBP as a time-update covariate, changes in SBP did not influence the effect of empagliflozin on the primary endpoint.
  • Empagliflozin attenuated the slope of eGFR decline similarly in all SBP categories. Also the risk reduction of the renal composite endpoint by empagliflozin was similar in SBP categories.


In patients with HFrEF in the EMPEROR-Reduced trial, the SGLT2 inhibitor empagliflozin reduced the risk of the primary endpoint, HF hospitalization and renal outcomes independently of baseline SBP. Empagliflozin treatment was well tolerated in patients in the low SBP group (<110 mmHg) and these patients had no decline in SBP and no increased risk of hypotension.


1. Kario K, Okada K, Kato M, et al. 24-Hour blood pressure-lowering effect of an SGLT-2 inhibitor in patients with diabetes and uncontrolled nocturnal hypertension: results from the randomized, placebo-controlled SACRA study. Circulation.2018;139:2089–2897.

2. Chilton R, Tikkanen I, Hehnke U, Woerle HJ, Johansen OE. Impact of empagliflozin on blood pressure in dipper and non-dipper patients with type 2 diabetes mellitus and hypertension. Diabetes Obes Metab. 2017;19:1620–11624.

3. Böhm M, Ewen S. Blood pressure risk associations in heart failure: true effects or inverse causality? J Am Coll Cardiol HF. 2017;5:820–822.

4. Khattab M, Parwani P, Abbas M, et al. Utilization of guideline-directed medical therapy in patients with de novo heart failure with reduced ejection fraction: a Veterans Affairs study. J Family Med Prim Care. 2020;9:3065–3069.

5. Komajda M, Böhm M, Borer JS, et al. SHIFT Investigators. Efficacy and safety of ivabradine in patients with chronic systolic heart failure according to blood pressure level in SHIFT. Eur J Heart Fail. 2014;16:810–816

Find this article online at J Am Coll Cardiol

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