Key result
ACEIs linked to ~15% higher 5-year risk of neurocognitive disorders versus ARBs in HFrEF.
Why the study?
To compare 5-year cognitive outcomes in patients with HFrEF who receive ACEIs versus ARBs.
Do angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of cognitive decline compared to angiotensin receptor blockers (ARBs) in adults with HFrEF?
Cohort (n=271,746)
Yes
Do angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of cognitive decline compared to angiotensin receptor blockers (ARBs) in adults with HFrEF?
Effect estimate: HR 1.153 (95% CI 1.129-1.178)
Absolute Event Rate: 30.71% vs 28.54%
p-value: p=<0.001
In patients with HFrEF, the use of ACE inhibitors is associated with a higher 5-year risk of neurocognitive disorders compared to ARBs.
ACEI use was associated with higher cognitive event rates than ARB in HFrEF; leaves open whether ARBs confer cognitive benefit.
OBJECTIVE: Aim: To compare 5-year cognitive outcomes in patients with HFrEF who receive angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). PATIENTS AND METHODS: Materials and Methods: Retrospective cohort study of: 1) 135,873 adults with HFrEF (International Classification of Diseases-10th Revision-Clinical Modification [ICD-10-CM] codes: I50.2 or I50.4) started on ACEI between Aug 1, 2019 and Aug 1, 2024; and 2) 135,873 propensity matched patients receiving ARBs during that time. Data were obtained from the TriNetX Research Network, encompassing 80 health care organizations in the United States. The primary endpoint was the composite of cognitive decline (ICD-10-CM: R41.8), dementia (ICD-10-CM: F01-F03), and Alzheimer's disease (ICD-10- CM: G30). RESULTS: Results: At 5 years,17,679 patients on ACEI met the primary endpoint vs 16,345 patients on ARBs (5-year incidence: 30.71% vs 28.54%; HR: 1.153; 95% CI: 129-1.178; P < 0.001), with consistently higher rates of cognitive decline (24.94% vs 22.81%; HR: 1.146; 95% CI: 1.119-1.174; P < 0.001), dementia (15.63% vs 13.71%; HR:1.204; 95% CI: 1.168-1.241; P < 0.001), and Alzheimer's disease (4.15% vs 3.51%; HR: 1.202; 95% CI: 1.131-1.277; P < 0.001) in the ACEI cohort. CONCLUSION: Conclusions: ACEI was associated with higher 5-year rates of neurocognitive disorders when compared to ARBs in patients with HFrEF.
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Rhabneh et al. (2026) conducted a cohort in Heart Failure with Reduced Ejection Fraction (HFrEF) (n=271,746). Angiotensin-converting enzyme inhibitors (ACEIs) vs. Angiotensin receptor blockers (ARBs) was evaluated on Composite of cognitive decline, dementia, and Alzheimer's disease (HR 1.153, 95% CI 1.129-1.178, p=<0.001). Angiotensin-converting enzyme inhibitors were associated with a higher 5-year incidence of neurocognitive disorders compared to angiotensin receptor blockers in patients with HFrEF (HR 1.153).
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