Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors Secondary to Hyperkalemia Translates into Higher Cardiorenal Outcomes

Abstract

Introduction: Discontinuation of renin-angiotensin-aldosterone system inhibitor (RAASi) is common after hyperkalemia. We evaluated the risk of kidney and mortality outcomes associated with RAASi discontinuation among patients with chronic kidney disease (CKD) and hyperkalemia. Methods: We identified adult patients with CKD (eGFR <60 mL/min/1.73 m2) who experienced new-onset hyperkalemia (potassium ≥5.0 mEq/L) between 2016 and 2017 from Kaiser Permanente Southern California and followed them through 2019. We defined treatment discontinuation as having ≥90-day gap in refills of all RAASi within 3 months after hyperkalemia. We used multivariable Cox proportional hazards models to evaluate the association between RAASi discontinuation and the primary composite outcome of kidney (≥40% eGFR decline, dialysis, kidney transplant) or all-cause mortality. We evaluated cardiovascular events and recurrence of hyperkalemia as secondary outcomes. Results: Among 5,728 patients (mean age 76 years), 13.5% discontinued RAASi within 3 months after new-onset hyperkalemia. During the median 2 years of follow-up, 29.7% had the primary composite outcome (15.5% with ≥40% eGFR decline, 2.8% dialysis or kidney transplant, 18.4% all-cause mortality). Patients who discontinued RAASi had a higher all-cause mortality compared with those who continued RAASi (26.7% vs. 17.1%) but had no differences in kidney outcomes, cardiovascular events, and recurrence of hyperkalemia. RAASi discontinuation was associated with a higher risk of kidney or all-cause mortality composite outcome (adjusted hazard ratio [aHR] 1.21, 95% CI: 1.06, 1.37) mainly driven by all-cause mortality (aHR: 1.34, 95% CI: 1.14, 1.56). Conclusion: RAASi discontinuation after hyperkalemia was associated with worsened mortality, which may underscore the benefits of continuing RAASi among patients with CKD.