Initial Decline (“Dip”) in Estimated Glomerular Filtration Rate Following Initiation of Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: Insights From DAPA-HF
Circulation 2022; Online ahead of print doi: 10.1161/CIRCULATIONAHA.121.058910
The results of this subgroup analysis from DAPA-HF show that – although estimated glomerular filtration rate (eGFR) decline is generally associated with poorer prognosis in most situations – an initial dip with a sodium-glucose co-transporter-2 inhibitor (SGLT2i) may be associated with slower rate of decline in kidney function.
SGLT2i reduce the risk of worsening heart failure (HF) and cardiovascular (CV) death in patients with HF with reduced ejection fraction (HFrEF). These agents also reduce the long-term rate of decline in eGFR and development of end-stage kidney disease in patients with HFrEF, and those with chronic kidney disease – with or without type 2 diabetes (T2D). However, the fact that SGLT2i cause an initial decline in eGFR has raised some clinical concern, particularly for patients with reduced eGFR at baseline.
Previous analyses of the early eGFR decline with SGLT2i have been in patients with T2D, but the renal pathophysiology may be different in HFrEF, since this group often have low blood pressure and fluctuations in plasma volume.
DAPA-HF was a randomised double-blind, placebo-controlled, event-driven trial in patients with HFrEF, with or without T2D. Once-daily dapagliflozin 10 mg was compared to matching placebo, and taken in addition to standard treatment. The subgroup analysis reported by Adamson and colleagues measured kidney function and eGFR. Findings showed the average dip in eGFR after starting dapagliflozin was small and associated with better clinical outcomes, compared with a similar decline on placebo in patients with HFrEF. Large declines in eGFR were uncommon with dapagliflozin. The authors conclude that an initial decline in eGFR after initiation of an SGLT2i should not usually lead to discontinuation of treatment.