From the Guidelines
SGLT2 inhibitors are recommended for patients with heart failure with reduced ejection fraction (HFrEF) regardless of diabetes status, and should be initiated as soon as the diagnosis of HFrEF is established and the patient is clinically stable, even during hospitalization before discharge, according to the most recent guidelines 1. The UK and European guidelines suggest that SGLT2 inhibitors (dapagliflozin 10mg daily or empagliflozin 10mg daily) should be initiated in patients with symptomatic HFrEF (LVEF ≤40%) who are already on standard heart failure therapy including ACE inhibitors/ARBs/ARNI, beta-blockers, and MRAs. These medications reduce cardiovascular mortality and heart failure hospitalizations, as shown in recent studies 1. Some key points to consider when initiating SGLT2 inhibitors include:
- Contraindications: type 1 diabetes, eGFR <30 ml/min/1.73m², pregnancy/breastfeeding, recurrent genital infections, and hypersensitivity to the medication.
- Caution is advised in patients at risk for volume depletion, diabetic ketoacidosis, or those on insulin/sulfonylureas due to hypoglycemia risk.
- Patients should be counseled about potential side effects including genital infections, urinary tract infections, and volume depletion.
- Regular monitoring of renal function is recommended, especially in patients with pre-existing renal impairment. The mechanism of action of SGLT2 inhibitors involves promoting glycosuria and natriuresis, reducing cardiac preload and afterload, improving cardiac metabolism, and providing cardiorenal protection through multiple mechanisms beyond glucose control, as described in recent guidelines 1. In terms of specific patient populations, the guidelines suggest that SGLT2 inhibitors can be used in patients with HFrEF, as well as those with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) 1. Overall, the use of SGLT2 inhibitors in patients with HFrEF has been shown to improve outcomes and reduce morbidity and mortality, and should be considered as part of a comprehensive treatment plan, as recommended by recent guidelines 1.
From the Research
UK and European Guidelines on Starting SGLT2 Inhibitors
- The guidelines emphasize the importance of starting SGLT2 inhibitors as quickly as possible for patients with heart failure and reduced ejection fraction, with titration to target dose as a secondary consideration 2.
- The UK and European guidelines recommend SGLT2 inhibitors, such as empagliflozin and dapagliflozin, for patients with heart failure with reduced ejection fraction (HFrEF) to reduce adverse cardiovascular outcomes 3, 4, 5, 6.
Indications for SGLT2 Inhibitors
- Patients with HFrEF and a left ventricular ejection fraction ≤40% are eligible for SGLT2 inhibitors 3, 4, 5.
- SGLT2 inhibitors can be used in patients with and without diabetes, as they have been shown to reduce cardiovascular and renal outcomes in both populations 3, 4, 5, 6.
- The guidelines suggest that SGLT2 inhibitors can be considered as a foundational therapy in patients with HFrEF, regardless of their existing background therapy 4.
Contraindications for SGLT2 Inhibitors
- The major determinant of ineligibility for SGLT2 inhibitors is the failure to achieve the predefined NT-proBNP inclusion threshold 5.
- Other contraindications may include severe renal impairment, hypotension, and hyperkalemia, although the incidence of these adverse events was similar across all subgroups in clinical trials 4.
Ideal Time of Initiation
- The guidelines recommend starting SGLT2 inhibitors as quickly as possible, with titration to target dose as a secondary consideration 2.
- The ideal time of initiation may vary depending on individual patient factors, such as the severity of heart failure and the presence of comorbidities, but the guidelines suggest that SGLT2 inhibitors can be initiated early in the treatment of HFrEF 3, 4, 5, 6.