Emerging role for SGLT2 inhibitors in mitigating the risk of
In their investigation of 9583 patients included in either the EMPEROR-Reduced or EMPEROR-Preserved trials, randomization to empagliflozin was associated with an 18% risk reduction in the main composite endpoint of investigator-reported hyperkalaemia or initiation of potassium binders. These findings were consistent across the spectrum of ejection fraction, as well as across other pre-specified subgroups including BMI, race, MRA use, and others, although patients with diminished renal function and hospitalization for HF in the last 12 months tended to have more pronounced benefits. Importantly, empagliflozin demonstrated this benefit without increasing the incidence of hypokalaemia. Beyond the primary results, the sub-analysis also yielded a variety of other notable findings including more significant HF and comorbidity burden amongst patients with baseline potassium >5.0 mmol/L. This subset of patients also experienced an attenuation of empagliflozin’s effect on the primary composite of hospitalization for HF or CV death, as well as first and total hospitalization for HF. Empagliflozin’s reduction of the extended composite outcome incidence, which captures both inpatient and outpatient indices of worsening HF, as well as its impact on the slope of eGFR decline, was consistent regardless of baseline potassium.

These findings reinforce a consistent signal emerging from the sodium-glucose cotransporter -2 (SGLT2) inhibitor literature. Previous sub-analyses from the EMPEROR dataset demonstrated an ability for empagliflozin to significantly reduce hyperkalaemia events regardless of background MRA use in both patients with preserved and reduced ejection fraction. Similarly, a sub-analysis of the 70% of patients included in DAPA-HF that were treated with an MRA yielded a 50% reduction in the risk of moderate/severe hyperkalaemia (potassium >6.0 mmol/L), as well as a 36% reduction in the same amongst all patients regardless of MRA use.

Outside of exclusively HF trials, data from the CREDENCE trial, which included patients with T2DM and CKD, demonstrated a 22% reduction in the risk of investigator-reported hyperkalaemia or initiation of potassium binders with randomization to canagliflozin, with no increase in the rates of hypokalaemia.

Source: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac304/6604931?rss=1&login=true