Effect of SGLT2 inhibitor on CV death or HF hospitalization in HFpEF independent of SBP

Empagliflozin, irrespective of blood pressure, improves outcomes in heart failure with preserved ejection fraction: the EMPEROR-Preserved trial

Literature - Böhm M, Anker S, Mahfoud S, et al. - Eur Heart J. 2022 Dec 7;ehac693. doi: 10.1093/eurheartj/ehac693.

Introduction and methods

Background

The EMPEROR-Preserved trial previously showed that the SGLT2 inhibitor empagliflozin reduces the risk of cardiovascular death or first hospitalization for HF in patients with HF and an LVEF >40% (HFpEF), compared with placebo [1]. It is unclear whether this effect is modified by SBP.

Aim of the study

This secondary post-hoc analysis of the EMPEROR-Preserved trial examined whether the effect of empagliflozin in patients with HFpEF is modified by SBP.

Methods

In the international, multicenter, double-blind EMPEROR-Preserved trial, 5988 adult patients with chronic HF and an LVEF >40% were randomized to empagliflozin or placebo, in addition to usual therapy. Patients with NYHA class II-IV symptoms and a NT-proBNP level >300 pg/mL who had been hospitalized for HF in the past 12 months or in whom structural abnormalities were found on echocardiography were eligible to participate in this phase 3 study. BP was taken in a sitting position after 5 min of rest. The mean of three attended BP measurements was calculated. In this secondary post-hoc analysis, patients were divided into 3 groups based on their SBP at study entry: <110 mmHg (n=455); 110-130 mmHg (n=2415); and >130 mmHg (n=3118).

Outcomes

The primary outcome was a composite of the time to cardiovascular death or first hospitalization for HF. Secondary outcomes were time to first and recurrent hospitalization for HF and the change in eGFR slope (in mL/min per 1.73 m2 per year). Also examined were the effect of empagliflozin on blood pressure and adverse events.

Main results

  • The incidence rate of cardiovascular death or first hospitalization for HF was 8.58, 8.26 and 11.59 per 100 person-years for patients with SBP >130, 100-130 or<130 mmHg, respectively (>130 vs. <110 mmHg: P=0.12; 110-130 vs. <110 mmHg: P=0.08).
  • Compared with placebo, empagliflozin improved the time to cardiovascular death or first hospitalization for HF across all SBP groups (HR [95%CI]: >130 mmHg: 0.82 [0.68-0.98]; 110-130 mmHg: 0.78 [0.63-0.96]; <110 mmHg: 0.67 [0.43-1.03]), without a significant difference between SBP groups (P-interaction=0.69).
  • Similar results were found for the time to first hospitalization for HF (HR [95%CI]: >130 mmHg: 0.75 [0.60-0.94]; 110-130 mmHg: 0.63 [0.49-0.81]; <110 mmHg: 0.85 [0.50-1.43]; P-interaction=0.46) and recurrent hospitalization for HF (P-interaction=0.55).
  • Compared with placebo, empagliflozin reduced the eGFR slope across all SBP groups (difference in slope [95%CI]: >130 mmHg: 1.315 [0.901-1.730]; 110-130 mmHg: 1.586 [1.118-2.054];<110 mmHg: 0.508 [-0.608-1.623]), with a significant difference between SBP groups (P-interaction <0.0001).
  • Treatment with empagliflozin resulted in a modest (2-4 mmHg) placebo-correct decrease in SBP and DBP, with no significant difference between SBP groups (P-interaction >0.1 for SBP and DBP).
  • The incidence of adverse events, such as hypotension, volume depletion, and acute renal failure, was lower in the empagliflozin group than in the placebo group across all SBP groups.
  • The incidence rates of adverse events, such as volume depletion, hypotension, and symptomatic hypotension, were higher at lower SBP and numerically higher on empagliflozin than on placebo; nevertheless, the incidence rates of these adverse events were low.

Conclusion

This secondary post-hoc analysis of the placebo-controlled EMPEROR-Preserved trial shows that empagliflozin significantly improves the time to cardiovascular death or first hospitalization for HF in patients with HFpEF, independent of SBP.

References

1. Anker SD, Butler J, Filippatos G, et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451-61.

Find this article online at Eur Heart J.

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