From the Guidelines
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are strongly recommended for patients with heart failure with preserved ejection fraction (HFpEF) based on compelling clinical evidence from the most recent study 1. The EMPEROR-Preserved trial demonstrated that empagliflozin 10 mg daily reduced the combined risk of cardiovascular death and heart failure hospitalizations by 21% in HFpEF patients, regardless of diabetes status 1.
Key Benefits of SGLT2i in HFpEF
- Reduced risk of heart failure hospitalizations and cardiovascular mortality
- Improved quality of life
- Additional benefits including weight loss and renal protection
Initiation and Monitoring of SGLT2i
- SGLT2i should be initiated at standard doses (empagliflozin 10 mg daily or dapagliflozin 10 mg daily) without titration
- Patients should be counseled about potential side effects including genital mycotic infections, urinary tract infections, and volume depletion
Mechanism of Action
- SGLT2i work through multiple mechanisms including improved cardiac energetics, reduced cardiac fibrosis, decreased inflammation, and beneficial effects on renal sodium handling The 2024 update to the 2020 ACC/AHA clinical performance and quality measures for adults with heart failure also supports the use of SGLT2 inhibitors in patients with HFpEF, with a Class 2a recommendation and Level of Evidence: B-R 1.
Clinical Recommendations
- In patients with HFpEF, SGLT2 inhibitors can be beneficial in decreasing HF hospitalizations and cardiovascular mortality
- SGLT2 inhibitors should be considered as part of the treatment plan for patients with HFpEF, especially those with comorbidities like obesity, diabetes, and chronic kidney disease.
From the Research
Overview of SGLT2 Inhibitors in HFpEF
- SGLT2 inhibitors have been identified as a potential therapeutic option for patients with heart failure with preserved ejection fraction (HFpEF) 2, 3, 4, 5, 6.
- These inhibitors have shown promise in reducing hospitalization for heart failure and improving quality of life in patients with HFpEF 3, 5.
Mechanisms and Clinical Applications
- SGLT2 inhibition promotes natriuresis and osmotic diuresis, leading to plasma volume contraction and reduced preload, and decreases in blood pressure, arterial stiffness, and afterload 4.
- SGLT2 inhibition is also associated with preservation of renal function and improvement in diastolic dysfunction parameters 4, 5.
Clinical Trials and Evidence
- The EMPA-REG OUTCOME trial and the CANVAS trial demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes mellitus and cardiovascular disease treated with SGLT2 inhibitors 4.
- The EMPEROR-Preserved study showed that therapy with the SGLT2 inhibitor empagliflozin significantly reduced hospitalization for heart failure in patients with HFpEF 5.
- A literature review of clinical trials and meta-analyses found that SGLT2 inhibitors improved the combined outcome of CV death and hospitalization for heart failure in patients with HFpEF 3.
Patient Benefits and Future Directions
- Patients with HFpEF and NYHA class II-III with frequent symptoms or hospitalizations for heart failure may derive the most benefit from SGLT2 inhibitors 3.
- Further studies are needed to determine the extent to which SGLT2 inhibitors will lead to an improvement in the prognosis of patients with HFpEF 5, 6.