Effects of Hyperkalaemia and Non-Adherence to Renin–Angiotensin–Aldosterone System Inhibitor Therapy in Patients with Heart Failure in Italy: A Propensity-Matched Study

AIMS: The aims of this study were to evaluate if the risk of cardiovascular events and all-cause mortality was higher in the presence of hyperkalaemia (HK) in patients with heart failure (HF) treated with renin-angiotensin-aldosterone system inhibitors (RAASi), and to investigate in this cohort the increased risk of cardiovascular events and all-cause mortality among HK patients with non-optimal adherence to RAASi therapy. METHODS AND RESULTS: In this retrospective cohort study based on administrative databases of five Italian Local Health Units, all adult patients with a HF diagnosis between January 2010 and December 2017 were included only if they were prescribed RAASi therapy during the first 3 months after the index date, that corresponded to the date of first HF diagnosis during the inclusion period. Patients were considered to have HK if serum potassium level was ≥5.5 mmol/L. A propensity score matching was applied before evaluation of hazard ratios. Patients with HK were 37% (P < 0.001) and 70% (P < 0.001), respectively, more at risk of cardiovascular events and of dying for all-cause mortality compared to non-HK patients. Among the HK group, patients non-adherent to RAASi therapy had a 39% (P = 0.105) higher risk of cardiovascular events and a twofold increased risk (P < 0.001) of all-cause death. CONCLUSION: Findings from this real-world study showed that in a cohort of HF patients under RAASi therapy, subjects with HK had an enhanced risk of cardiovascular events or death compared to patients without HK. Moreover, in HK patients, sub-optimal adherence to RAASi therapy was associated with an increased risk of all-cause mortality.