Potassium and the use of renin–angiotensin–aldosterone system inhibitors in heart failure with reduced ejection fraction: data from BIOSTAT-CHF

Background: Hyperkalemia is a common comorbidity in patients with heart failure with reduced ejection fraction (HFrEF). Whether it affects the use of RAAS-inhibitors and thereby negatively impacts outcome is unknown. Therefore, we investigated the association between potassium and uptitration of ACE-inhibitor/ARB and its association with outcome.
Methods and results: Out of 2,516 patients from the BIOSTAT-CHF study, potassium levels were available in 1,666 patients with HFrEF. These patients were sub-optimally treated with ACEi/ARB or beta-blockers and were anticipated and encouraged to be uptitrated. Potassium levels were available at inclusion and 9 months. Outcome was a composite of all-cause mortality and HF-hospitalization at 2 years.Patients were 67±12 years old and 77% was male. At baseline, median serum potassium was 4.2(3.9–4.6) mEq/L. After 9 months, 401 (24.1%) patients were successfully uptitrated for ACEi/ARB. During this period, mean serum potassium increased by 0.16±0.66 mEq/L (p<0.001). Baseline potassium was an independent predictor for lower obtained dosages of ACEi/ARB (OR 0.70; 95%CI 0.51–0.98). An increase in potassium was not associated with adverse outcomes (HR 1.15; 95%CI 0.86–1.53). No interaction was found between baseline potassium, potassium increase during uptitration or potassium at 9 months and an increase of dose of ACEi/ARB for outcome (pinteraction for all >0.5).
Conclusion: Higher potassium levels are an independent predictor of enduring lower dosages of ACEi/ARB. Higher potassium levels do not attenuate the beneficial effects of uptitration ACEi/ARB.