AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Cardiovascular and Renal Outcomes of Renin-Angiotensin-Aldosterone System Inhibitor Continuation versus Discontinuation in Patients with Heart Failure and Chronic Kidney Disease Stage 3a: A Propensity Matched Real World Analysis
By Bakhle R, Vanani S, Ali M et al.
Introduction: Renin angiotensin aldosterone system inhibitors (RAASi) are integral in the management of chronic kidney disease (CKD) and heart failure (HF), yet there is ongoing clinical uncertainty regarding their continuation following a new CKD stage 3a diagnosis with coexisting HF. Real-world data examining outcomes in this overlapping, high-risk population is limited. This study uses a large federated electronic health record (EHR) network to compare clinical outcomes between patients with new-onset CKD stage 3a and comorbid HF who continued versus discontinued RAASi at the time of CKD diagnosis. Methods: We performed a retrospective comparative outcomes analysis using the TriNetX network. Adults (≥18 years) with ICD-10 coded new-onset CKD stage 3a, baseline eGFR ≥60 mL/min/1.73 m ² , pre-existing HF, and prior RAASi exposure were identified. Cohort A (n=4,682) continued RAASi through CKD diagnosis; Cohort B (n=2,684) discontinued RAASi within three months of diagnosis. Patients with CKD stage 3b or greater, ESKD, or aliskiren use were excluded. Propensity score matching for demographics, cardiometabolic comorbidities, concomitant medications, and baseline laboratories yielded 2,454 matched pairs. Outcomes of all-cause mortality, CKD stage 4 and 5 progression, ESKD, acute MI, stroke, and severe hyperkalemia (K ⁺ ≥6.0 mmol/L) were assessed over two years using Kaplan-Meier with log-rank testing and risk ratio estimation. Results: RAASi continuation was associated with a statistically significant reduction in all-cause mortality. Two-year mortality risk was 2.3% in continuers vs 3.4% in discontinuers (HR 0.677, 95% CI 0.482-0.950; log-rank p=0.023). A significant attenuation in CKD stage 4 progression was observed: 6.5% in the RAASi group vs 8.0% in the non-RAASi group (HR 0.807, 95% CI 0.655-0.995; log-rank p=0.044). However, progression to ESKD (HR 0.835, p=0.247) and CKD stage 5 (HR 1.087, p=0.692) did not differ significantly between groups. Similarly, severe hyperkalemia rates were similar across the cohorts (3.3% vs. 2.8%; HR 1.184, 95% CI 0.846-1.655; p=0.324). While the stroke risk was comparable (HR 1.028, p=0.815), acute MI risk was higher in the RAASi group (8.4% vs 6.6%; HR 1.281, 95% CI 1.013-1.619; log-rank p=0.038), a finding that warrants cautious interpretation given the observational design and potential residual confounding. Conclusion: In this large, propensity-matched real-world cohort with new-onset CKD stage 3a and comorbid HF, RAASi continuation was associated with reduced all-cause mortality and slowed progression to CKD stage 4, without a significant increase in severe hyperkalemia risk. These findings support continued RAASi use in this high-risk population, while the observed MI finding underscores the need for prospective studies to further clarify the cardiovascular risk profile of RAASi in this complex population.