Dapagliflozin reduces hyperkalaemia risk in heart failure with reduced EF: Study

Researchers have presented the findings in European Society of Cardiology virtual congress.

Spironolactone and eplerenone are both mineralocorticoid-receptor antagonists. These compounds block both the epithelial and nonepithelial actions of aldosterone, with the latter assuming increasing clinical relevance.

The mineralocorticoid receptor antagonists (MRAs), spironolactoneand eplerenone, are recommended for patients with symptomatic heart failure with ejection fraction of 35% or less. Owing to their capacity to lower blood pressure and to reduce the risk of cardiovascular complications and mortality in large randomized, placebo‐controlled trials ,MRAs are documented to be effective in such patients.

But,risks of hyperkalemia and worsening renal function often limit use of MRA therapy in patients with heart failure. Current management of hyperkalaemia is most often centred on eliminating modifiable causes, e.g. lowering dietary potassium (K⁺) intake, and/or discontinuing or lowering the dose of hyperkalaemia‐inducing medications.this has proved to be of great setback for HF patients.

To bridge this gap , SL Kristensen and associates ,at the Copenhagen University Hospital - Copenhagen – Denmark, carried out a study 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.

In a secondary analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, 3370 (70.1%) patients were treated with an MRA. Patients were divided into 2 groups-on dapagliflozin and placebo group. The risk of developing mild hyperkalaemia (potassium > 5.5 mmol/L) and moderate/severe hyperkalaemia (>6.0 mmol/L) was examined.

Results of the study revealed the following key facts.

· 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.

· 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.

· The incidence of moderate-to-severe hyperkalemia was reduced from 1.7 to 1.0 per 100 person-years with dapagliflozin.

"Dapagliflozin reduced the risk for mild hyperkalemia by 14% and moderate-to-severe hyperkalemia by 50% (P =.01) compared with placebo."said the researchers.

Primary source: Kristensen SL, Docherty KF, Jhund PS, et al. Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF. Presented at ESC Virtual Congress 2020, August 29, 2020.