Abstract
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.
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.
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.
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.
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 |
| 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.
Type of funding source: Private company. Main funding source(s): DAPA-HF study was funded by AstraZeneca
