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SGLT2HFHK
Integrating SGLT2 Inhibitors Across the Spectrum of Heart Failure to Improve Hyperkalemia

Released: November 09, 2023

Expiration: November 09, 2024

Biykem Bozkurt
Biykem Bozkurt, MD, PhD, FHFSA
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Key Takeaways
  • SGLT2 inhibitors are recommended for individuals with heart failure across the spectrum of ejection fraction.
  • SGLT2 inhibitors and angiotensin receptor-neprilysin inhibitor therapy are associated with slowing of the decline in eGFR and lower incidence of hyperkalemia compared to previous treatments, enabling guideline-directed medical therapy.

Where do sodium-glucose cotransporter-2 (SGLT2) inhibitors play a role in current guideline-directed medical therapy for heart failure (HF)?

If we look at the armamentarium of guideline-recommended medications across the spectrum of HF, we see that SGLT2 inhibition has a roll across all HF stages. Individuals with diabetes are considered stage A, or “at risk” for HF. The American Heart Association/American College of Cardiology/Heart Failure Society of America 2022 guidelines recommend SGLT2 inhibition in patients with diabetes with risk for cardiovascular disease. In stage B, or pre-HF, individuals do not have signs or symptoms of HF, but may have structural or functional cardiac changes (including low ejection fraction, diastolic dysfunction, or biomarker abnormalities, such as elevated natriuretic peptide levels). Patients with diabetes and with evidence of pre-HF should also receive an SGLT2 inhibitor.

The third stage is Stage C, symptomatic HF. The guidelines recommend four classes of medications in patients with HF with reduced ejection fraction (HFrEF) as the first step of treatment and as a class I recommendation. These include SGLT2 inhibitors, beta blockers, mineralocorticoid receptor antagonist (MRA), and RAAS inhibition, with either ACE inhibitors or ARB in NYHA Class II-IV, or angiotensin receptor-neprilysin inhibitor (ARNI) in NYHA Class II-III. Additional therapies in patients with HFrEF include hydralazine and nitrates which are indicated in Black patients (Class I recommendation), consideration of ivabradine in patients with heart rate over 70 beats/min despite beta blockers (Class IIA), vericiguat in patients with recent hospitalizations and elevated natriuretic peptide levels (Class IIB), and digoxin in symptomatic patients with HFrEF (Class IIB). In patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), the 2022 US guidelines recommended SGLT2 inhibitors with a Class IIA indication. That being said, the ESC guidelines which were published in August of 2023 have given SGLT2 inhibitors a Class 1 recommendation for both HFmrEF and HFpEF. This is based on the evidence from 2 large trials, EMPEROR-PRESERVED and DELIVER. These trials demonstrated significant improvement in cardiovascular death and HF hospitalization with the use of SGLT2 inhibitors in individuals with HFmrEF and HFpEF.

What role does SGLT2 inhibition play in the amelioration of hyperkalemia in HF?

SGLT2 inhibition is recommended across the continuum of ejection fraction in Stage C HF, including reduced, mildly reduced, and preserved ejection fractions, regardless of diabetes status. SGLT2 inhibitors are associated with a lower incidence of hyperkalemia and have been shown to enable initiation and continuation of MRA. By integrating SGLT2 inhibitors across the spectrum of care, we enable our patients to maintain normokalemia while keeping RAAS inhibition on board.

In addition, SGLT2 inhibitors and ARNI are associated with a lesser risk of worsening kidney function. They slow eGFR decline vs their comparator. SGLT2 inhibitors have also been shown to prevent kidney failure and development of end stage renal disease. ARNI is also associated with less risk of rise in creatinine or potassium when compared to ACE inhibitors or ARBs. So with that in mind, they actually can facilitate and enable initiation of  RAASi in a successful manner.

Your Thoughts? 
If you are interested in learning more, go online to view the CME/CE certified webinar recording from the live HFSA 2023 session, or join the conversation below.

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In your current practice, how often are you initiating SGLT2 inhibitors for HF?

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