Incidence, Predictors and Outcomes Related to Hypo and Hyperkalemia in Severe Heart Failure Patients Treated with a Mineralocorticoid Receptor Antagonist
Background—Mineralocorticoid receptor antagonists (MRA) reduce morbidity and mortality in heart failure but can cause hyperkalemia, which contributes to reduced utilization of these drugs. Hypokalemia also leads to worse outcomes in patients with heart failure and may be attenuated by MRA.
Methods and Results—We assessed incidence and predictors of hyperkalemia (potassium ≥ 5.5 mmol/L) and hypokalemia (potassium < 3.5 mmol/L) and the relationship to outcomes in 1663 patients with class III or IV HF and LVEF < 35% randomized to treatment with spironolactone 25mg or placebo in the Randomized Aldactone Evaluation Study (RALES) trial. All-cause mortality rates and the influence of potassium levels on the effectiveness of spironolactone were assessed in a landmark analysis and in relation to time-varying potassium levels. After 1 month, mean potassium levels increased in the spironolactone group, but not in the placebo group (4.54 ± 0.49 versus 4.28 ± 0.50 mmol/L, p<0.001.), and remained elevated during the trial. While the extremes of hypokalemia and hyperkalemia at 4 weeks were associated with increased risk of mortality in both treatment arms, participants in the spironolactone arm had lower mortality rates at all potassium levels throughout the duration of the trial. The treatment benefit of spironolactone were maintained at least until potassium exceeded 5.5 mmol/L.
Conclusions—With appropriate surveillance of potassium and creatinine, use of spironolactone was associated with less hypokalemia and improved survival in patients with severe heart failure even in the setting of moderate hyperkalemia.
- Received January 10, 2014.
- Accepted April 30, 2014.