Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF

Abstract Background Hyperkalaemia often limits the use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure and reduced ejection fraction (HFrEF), denying these patients a life-saving therapy. Purpose To determine whether treatment with the sodium-glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin reduces the risk of hyperkalaemia associated with MRA use in patients with HFrEF. Methods The risk of developing mild hyperkalaemia (potassium >5.5 mmol/L) and moderate/severe hyperkalaemia (>6.0 mmol/L) was examined in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) according to background MRA use, and randomized treatment assignment, by use of Cox regression analyses. Results Overall, 3370 (70.1%) patients in DAPA-HF were treated with an MRA. Mild hyperkalaemia and moderate/severe hyperkalaemia occurred in 182 (11.1%) and 23 (1.4%) patients treated with dapagliflozin as compared to 204 (12.6%) and 40 (2.4%) of patients given placebo (Table and Figure). This yielded a hazard ratio (HR) of 0.86 (0.70–1.05) for mild hyperkalaemia and 0.50 (0.29, 0.85) for moderate/severe hyperkalaemia, comparing dapagliflozin to placebo. Conclusions Patients with HFrEF and taking a MRA who were randomized to dapagliflozin had half the incidence of moderate/severe hyperkalaemia, compared with those randomized to placebo. Incident hyperkalaemia in DAPA-HF Dapagliflozin Placebo HR (95% CI) P-value No. events/patients Rate per 100py No. events/patients Rate per 100py Mild hyperkalaemia (>5.5 mmol/L)* No MRA at baseline 63/661 7.1 58/684 6.5 1.20 (0.84–1.72) 0.32 MRA treated at baseline 182/1637 8.6 204/1626 9.8 0.86 (0.70–1.05) 0.14 All patients 245/2298 8.2 262/2310 8.8 0.93 (0.78–1.11) 0.42 Moderate/Severe hyperkalaemia (>6.0 mmol/L)** No MRA at baseline 13/676 1.4 11/697 1.1 1.17 (0.52–2.62) 0.71 MRA treated at baseline 23/1688 1.0 40/1667 1.7 0.50 (0.29–0.85) 0.010 All patients 36/2364 1.1 51/2364 1.6 0.64 (0.42–0.99) 0.046 Models adjusted for baseline potassium and stratified by diabetes status at randomization. *Excluding those with baseline K+ >5.5 (n=136); **Excluding those with baseline K+ >6.0 (n=16). Abbreviations: CI, confidence interval; HR, hazard ratio; MRA, mineralocorticoid receptor antagonist; PY, patient-years. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): DAPA-HF study was funded by AstraZeneca