Cerebrovascular Outcomes with Angiotensin Receptor-neprilysin Inhibitors in Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Parinda Ansusinha1, Natee Deepan2, Adivitch Sripusanapan3
1Faculty of Medicine, Srinakharinwirot University, 2Faculty of Medicine, Chulalongkorn University, 3Department of Internal Medicine, University of Hawaii
Objective:

This meta-analysis evaluates the effect of ARNI therapy on the occurrence of ischemic stroke, cerebral infarction, transient ischemic attack (TIA) and hemorrhagic transformation of ischemic stroke in HF patients. 

Background:
Heart failure (HF) is associated with increased risks of cerebrovascular events, including ischemic stroke. Angiotensin receptor-neprilysin inhibitors (ARNI) have shown benefits in the management of HF, however their impact on cerebrovascular outcomes remains unknown. 
Design/Methods:

A systematic literature search of MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted on studies comparing ARNI with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in HF patients. The primary outcome assessed was the incidence of ischemic stroke. Secondary outcomes included cerebral infarction, TIA and hemorrhagic transformation of ischemic stroke. A random-effects meta-analysis was performed to estimate the incidence of these events. 

Results:

A total of six randomized controlled trials involving 17,459 patients were included. ARNI therapy did not significantly reduce the incidence of ischemic stroke (OR 0.92, 95% CI:0.22-0.37) compared with control groups. Additionally, the incidence of cerebral infarction (OR 0.75, 95% CI: 0.49-1.15), TIA (OR 1.14, 95% CI: 0.70-1.83) and hemorrhagic transformation of ischemic stroke (OR 0.52, 95% CI: 0.10-2.62) were not different between groups. 

Conclusions:

In HF patients, ARNI offers no statistically significant reduction in the occurrence of ischemic stroke, cerebral infarction, TIA or hemorrhagic transformation of ischemic stroke when compared to ACEI/ARB therapy. While ARNI remains beneficial for cardiovascular endpoints, further studies are needed to clarify the cerebrovascular impact of ARNI therapy in HF patients. 

10.1212/WNL.0000000000213069
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