Continuation of dapagliflozin beneficial among HF patients with deteriorating kidney function

In a recent study, researchers have explored the safety and effectiveness of continuing treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors in heart failure patients, especially when their kidney function declines below certain thresholds. They found that elevated cardiovascular risks caused by the deterioration of eGFR were reduced by the use of dapagliflozin. 

The study results were published in the Journal of The American College of Cardiology. 

Heart failure (HF) and chronic kidney disease (CKD) have shared epidemiology and frequently coexist in clinical practice. SGLT2 inhibitors have become an essential component of heart failure management, but questions have lingered about their use as kidney function worsens. Previous research has shown that dapagliflozin has shown immense benefits in patients with stage IV chronic kidney disease. Hence researchers conducted a study to examine the safety and efficacy of dapagliflozin in patients with heart failure and when the estimated glomerular filtration rate (eGFR) falls below thresholds for initiation.

The study, conducted as a participant-level pooled analysis of the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials, involved 11,007 patients. Of these, 3.2% experienced a deterioration of their estimated glomerular filtration rate (eGFR) to less than 25 mL/min/1.73 m² during the follow-up period.

The primary focus of the investigation was to assess the impact of declining kidney function on the efficacy and safety of dapagliflozin, an SGLT2 inhibitor commonly used to treat heart failure. Patients experiencing a deterioration of eGFR were found to be at a higher risk of the primary composite outcome, which typically includes worsening heart failure or cardiovascular death. 

Key Findings: 

• The key revelation in the study was that the risk of the primary outcome was lower with dapagliflozin compared to a placebo, regardless of whether patients experienced deterioration of their eGFR or not.
• Patients who had kidney function decline derived a substantial benefit from dapagliflozin (HR: 0.53), and this was also observed in those whose kidney function remained stable (HR: 0.78).
• Importantly, there was no significant difference in the effectiveness of dapagliflozin between the two groups, as indicated by a p-value of 0.17.
• In terms of safety outcomes, patients with deteriorating eGFR faced an elevated risk of experiencing side effects, including drug discontinuation.
• Nevertheless, the rates of these safety outcomes were comparable between the group receiving dapagliflozin and the placebo group.

Thus, the study concludes that heart failure patients who experience a decline in their eGFR to below 25 mL/min/1.73 m² still derive significant benefits from the continuation of dapagliflozin treatment. Due to the lack of safety concerns between the two groups, the benefit-to-risk ratio may favor the continuation of dapagliflozin treatment in patients with heart failure, even if their kidney function worsens. These findings are a substantial advancement in the management of heart failure patients who also suffer from kidney disease. They provide compelling evidence that continuing SGLT2 inhibitor therapy, such as dapagliflozin, can be advantageous even as kidney function declines, without compromising patient safety. 

Further reading: Chatur S, Vaduganathan M, Claggett B, et al. Dapagliflozin in Patients With Heart Failure and Deterioration in Renal Function. J Am Coll Cardiol. 2023 Nov, 82 (19) 1854–1863.https://doi.org/10.1016/j.jacc.2023.08.026