From the Guidelines
Farxiga (dapagliflozin) is not recommended for patients with End-Stage Renal Disease (ESRD) who also have Congestive Heart Failure (CHF). The medication has limited efficacy in patients with severely reduced kidney function, particularly those with an estimated glomerular filtration rate (eGFR) below 25 mL/min/1.73m². According to the study by 1, the dose modifications for dapagliflozin include a contraindication for use in patients with eGFR <30 mL/min/1.73 m2, and the use is not recommended for glycemic control in patients with eGFR <45 mL/min/1.73 m2.
For patients with ESRD on dialysis, Farxiga is not indicated as its glucose-lowering and cardioprotective benefits are significantly diminished due to the drug's mechanism of action, which relies on functioning kidneys to inhibit sodium-glucose cotransporter-2 (SGLT2) in the proximal tubules. While Farxiga has shown benefits in patients with heart failure, including those with reduced ejection fraction, as seen in the DAPA-HF trial 1, these benefits are not expected to extend to ESRD patients.
Some key points to consider in managing CHF patients with ESRD include:
- The use of other heart failure medications such as beta-blockers, ACE inhibitors or ARBs, mineralocorticoid receptor antagonists, and potentially newer agents like sacubitril/valsartan as more appropriate therapeutic options.
- Regular monitoring of kidney function, electrolytes, and volume status remains essential in managing these complex patients.
- The importance of considering the patient's clinical characteristics, such as blood pressure, heart rate, presence of congestion, atrial fibrillation, and kidney (dys)function, when selecting and adjusting medications, as highlighted in the study by 1.
Overall, the management of CHF patients with ESRD requires a comprehensive and individualized approach, taking into account the latest evidence and guidelines, such as those outlined in the studies by 1, 1, and 1.
From the FDA Drug Label
• DAPAGLIFLOZIN TABLETS are not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1. 73 m2. DAPAGLIFLOZIN TABLETS are likely to be ineffective in this setting based upon its mechanism of action.
The use of Farxiga (dapagliflozin) in patients with End-Stage Renal Disease (ESRD) and Congestive Heart Failure (CHF) is not directly addressed in terms of a recommendation for its use in ESRD. However, given that ESRD implies a very low eGFR, the statement about not recommending its use for glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2 due to likely ineffectiveness based on its mechanism of action is relevant.
- Key Point: The drug's effectiveness in improving glycemic control is expected to be diminished in settings of significantly reduced renal function, such as ESRD.
- Clinical Decision: Given the information provided and the mechanism of action of dapagliflozin, its use in ESRD for CHF patients would need careful consideration, focusing on its potential benefits for heart failure rather than glycemic control, but the label does not provide a direct recommendation for use in ESRD. 2
From the Research
Use of Farxiga in ESRD for CHF Patients
- Farxiga (dapagliflozin) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has shown benefits in cardiac and renal diseases 3.
- The use of SGLT2 inhibitors, including Farxiga, in patients with end-stage kidney disease (ESKD) is being explored due to their potential to improve cardiovascular outcomes 4.
- A study found that dapagliflozin reduced the risk of kidney failure and cardiovascular death/heart failure hospitalization in patients with chronic kidney disease (CKD), with and without heart failure (HF) 5.
- The study also found that the risk reductions were similar in patients with and without HF, but the absolute risk reductions were larger in HF patients 5.
- However, it is noted that ESKD was an exclusion criterion for all major clinical trials of SGLT2 inhibitors, including Farxiga, and therefore efficacy data in dialysis patients is lacking 4.
- Another study suggests that SGLT2 inhibitors may provide cardiovascular benefits to dialysis patients, not only indirectly by preserving the remaining kidney function and improving anemia but also directly by lowering intracellular sodium and calcium levels, reducing inflammation, regulating autophagy, and alleviating oxidative stress and endoplasmic reticulum stress within cardiomyocytes and endothelial cells 4.
- The use of Farxiga in patients with ESRD and CHF may be considered, but it is essential to weigh the potential benefits and risks, including the increased risk of genital infections, urinary tract infections, and Fournier's gangrene 3.
- Further research is needed to evaluate the safety and effectiveness of Farxiga use among patients with ESKD and CHF 4, 6.