Congestive heart failure Sodium-glucose co-transporter 2 inhibitors

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Editor(s)-In-Chief: C. Michael Gibson, M.S., M.D.; Associate Editor(s)-In-Chief: Mitra Chitsazan, M.D.[1]

Overview

Sodium-glucose co-transporter 2 (SGLT2) inhibitors (dapagliflozin or empagliflozin) are recommended for patients with HFrEF regardless of the presence or absence of diabetes, in addition to optimal medical therapy with an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist.

Sodium-glucose co-transporter 2 inhibitors

Indications for Sodium-glucose co-transporter 2 inhibitors

According to the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, all patients should be on a Sodium-glucose co-transporter 2 inhibitors if: [1]

1. The left ventricular ejection fraction (LVEF) is ≤ 40%

AND

2. The patient is already taking an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist.

  • SGLT2 inhibitors should be administered for all patients with HFrEF regardless of diabetes status.

Background

  • In DAPA-HF trial- a phase 3, placebo-controlled trial- 4744 patients with NYHA class II–IV, and an LVEF ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive dapagliflozin (10 mg once daily) or placebo, in addition to OMT [2]. The primary outcome was a composite of worsening HF (hospitalization or an urgent visit resulting in i.v. therapy for HF) or cardiovascular (CV) death. Results showed that over a median of 18.2 months, dapagliflozin resulted in a 26% reduction in the primary endpoint. Similar benefits were seen in patients with and without diabetes.
  • In the EMPEROR-Reduced trial, 3730 patients with NYHA class II–IV, and an LVEF ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive empagliflozin (10 mg once daily) or placebo, in addition to OMT [3]. The primary outcome was a composite of CV death or hospitalization for worsening HF. Results showed that over a median of 16 months empagliflozin reduced the primary endpoint by 25%.
  • Therefore, dapagliflozin or empagliflozin are recommended for patients with HFrEF regardless of the presence or absence of diabetes, in addition to optimal medical therapy with an ACE-I/ARNI, a beta-blocker, and an MRA. SGLT2 inhibitors also have diuretic/natriuretic effects which may provide additional benefits in reducing volume overload and congestion and thus may allow a reduction in the need to loop diuretics.

Dosing

SGLT2 inhibitor [1] Starting dose Target dose
Dapagliflozin 10 mg QD 10 mg QD
Empagliflozin 10 mg QD 10 mg QD

Contraindications

  1. 1.0 1.1 McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M; et al. (2021). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J. 42 (36): 3599–3726. doi:10.1093/eurheartj/ehab368. PMID 34447992 Check |pmid= value (help).
  2. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA; et al. (2019). "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction". N Engl J Med. 381 (21): 1995–2008. doi:10.1056/NEJMoa1911303. PMID 31535829. Review in: Ann Intern Med. 2020 Feb 18;172(4):JC16
  3. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P; et al. (2020). "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure". N Engl J Med. 383 (15): 1413–1424. doi:10.1056/NEJMoa2022190. PMID 32865377 Check |pmid= value (help). Review in: Ann Intern Med. 2020 Nov 17;173(10):JC51