Cândida Fonseca1, Dulce Brito2, Patrícia Branco3, João Miguel Frazão4, José Silva-Cardoso5, Paulo Bettencourt6. 1. Heart Failure Clinic, São Francisco Xavier Hospital, Centro Hospitalar de Lisboa Ocidental (CHLO), Lisboa, Portugal; NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal. Electronic address: mcandidafonseca@gmail.com. 2. Cardiology Department, Centro Hospitalar Universitário Lisboa Norte (CHLN), Lisboa, Portugal; CCUL, Faculty of Medicine, Universidade de Lisboa, Lisboa, Portugal. 3. Nephrology Department, Santa Cruz Hospital, Centro Hospitalar de Lisboa Ocidental (CHLO), Carnaxide, Portugal. 4. Institute for Research and Innovation in Health Sciences (i3S) and Institute for Biomedical Engineering (INEB), Universidade do Porto, Porto, Portugal; Nephrology Department, Centro Hospitalar Universitário de São João (CHUSJ) and Faculty of Medicine, Universidade do Porto, Porto, Portugal. 5. Center for Health Technology and Services Research (CINTESIS), Porto, Portugal; Cardiology Department, Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal. 6. Internal Medicine Department, CUF Porto Hospital, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal.
Abstract
INTRODUCTION AND OBJECTIVES: Renin-angiotensin-aldosterone system inhibitors (RAASi) are the cornerstone of treatment of heart failure with reduced ejection fraction (HFrEF). RAASi optimization in real-life care is challenged by hyperkalemia, a potentially fatal adverse event, which can necessitate downtitration or discontinuation of RAASi and negatively impact survival in HFrEF. The literature on this problem is sparse. We performed a systematic review of studies on HFrEF to investigate the prevalence, incidence, and risk factors of hyperkalemia, RAASi prescription rates, frequency of RAASi downtitration or discontinuation due to hyperkalemia, and the potential negative effect of the latter on prognosis. METHODS: We conducted a MEDLINE (PubMed) search including observational and interventional studies published between January 1987 and May 2018. RESULTS: A total of 30 observational and 18 interventional studies were included in the review. The incidence of hyperkalemia reported was between 0% and 63% in observational studies and was between 0% and 30% in clinical trials. Risk factors for hyperkalemia included RAASi prescription, older age, diabetes, and chronic kidney disease. In real-life studies, RAASi were downtitrated or discontinued in 3-22% of HFrEF patients; hyperkalemia was the reported cause in 5% of cases. No reports were found on the impact on prognosis of RAASi downtitration or discontinuation due to hyperkalemia. CONCLUSIONS: Hyperkalemia and RAASi downtitration or discontinuation are frequent, particularly in real-life HFrEF studies. Further research is needed to clarify the role of RAASi downtitration or discontinuation due to hyperkalemia and to assess its long-term prognostic impact in HFrEF patients.
INTRODUCTION AND OBJECTIVES: Renin-angiotensin-aldosterone system inhibitors (RAASi) are the cornerstone of treatment of heart failure with reduced ejection fraction (HFrEF). RAASi optimization in real-life care is challenged by hyperkalemia, a potentially fatal adverse event, which can necessitate downtitration or discontinuation of RAASi and negatively impact survival in HFrEF. The literature on this problem is sparse. We performed a systematic review of studies on HFrEF to investigate the prevalence, incidence, and risk factors of hyperkalemia, RAASi prescription rates, frequency of RAASi downtitration or discontinuation due to hyperkalemia, and the potential negative effect of the latter on prognosis. METHODS: We conducted a MEDLINE (PubMed) search including observational and interventional studies published between January 1987 and May 2018. RESULTS: A total of 30 observational and 18 interventional studies were included in the review. The incidence of hyperkalemia reported was between 0% and 63% in observational studies and was between 0% and 30% in clinical trials. Risk factors for hyperkalemia included RAASi prescription, older age, diabetes, and chronic kidney disease. In real-life studies, RAASi were downtitrated or discontinued in 3-22% of HFrEF patients; hyperkalemia was the reported cause in 5% of cases. No reports were found on the impact on prognosis of RAASi downtitration or discontinuation due to hyperkalemia. CONCLUSIONS:Hyperkalemia and RAASi downtitration or discontinuation are frequent, particularly in real-life HFrEF studies. Further research is needed to clarify the role of RAASi downtitration or discontinuation due to hyperkalemia and to assess its long-term prognostic impact in HFrEF patients.