Down-Titration of RAASI and Recurrent Hyperkalemia

Down-titration, dose reduction or discontinuation, of renin-angiotensin-aldosterone system inhibitors (RAASi) is common following new-onset hyperkalemia. According to Hui Zhou, PhD, and colleagues, there are few data available on how RAASi down-titration is related to recurrent hyperkalemia.

The researchers conducted a retrospective cohort study to examine recurrent hyperkalemia and factors associated with RAASi down-titration in patients with chronic kidney disease (CKD) and/or heart failure. Results were reported during a poster session at the American Society of Nephrology Kidney Week 2022 in a poster titled Recurrent Hyperkalemia and Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Down-Titration in a US Integrated Healthcare System.

The study included adults with CKD and/or heart failure who experienced new-onset hyperkalemia at Kaiser Permanente Southern California. New-onset hyperkalemia was defined as potassium ≥5.0 mEq/L. Eligible patients had two or more fills of RAASi within 1 year prior to the index. Patients were followed up for up to 1 year.

Recurrent hyperkalemia was evaluated every 3 months from month 1 to month 9. Down-titration of RAASi was defined as ≥90 day gap in refills of one or more RAASi (discontinuation) or ≥25% dose reduction compared with the dose prior to the index. RAASi down-titration was evaluated in the following 3 months from month 4 to month 12. A secondary analysis using discontinuation as an outcome was also conducted. Factors associated with RAASi down-titration were identified using generalized estimating equation models.

The study cohort included 7875 patients. Among those patients, the percentages of RAASi dose reduction were stable at 17% in all 3-month periods. Discontinuation decreased from 12% to 7% in the last 3 months.

The percentage of recurrent hyperkalemia in the first month was 10%; the percentage in the last 3 months was 8%. There was an association between recurrent hyperkalemia and a higher likelihood of RAASi down-titration (rate ratio [RR], 1.36; 95% CI, 1.16-1.60) and discontinuation (RR, 1.75; 95% CI, 1.48-2.08). There was an association between inpatient recurrent hyperkalemia and worse kidney function and a higher likelihood of RAASi down-titration.

“After new-onset hyperkalemia, those who developed recurrent hyperkalemia were more likely to discontinue or reduce the dose of RAASi,” the authors said.

Source: Zhou H, Ni L, Sim JJ, et al. Recurrent hyperkalemia and renin-angiotensin-aldosterone system inhibitor (RAASi) down-titration in a US integrated healthcare system. FR-PO547. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2022; November 4, 2022; Orlando, Florida. Funding was provided by AstraZeneca.