Impact of heart failure medications on cognitive function: A systematic review

Background: Heart failure (HF) often coexists with cognitive impairment and accelerates cognitive decline. However, the impact of HF medications on cognition has received limited attention. This review evaluates the evidence on the cognitive effects of currently recommended medication classes for HF. Methods: Systematic review using PubMed and EMBASE following PRISMA guidelines, employing keywords related to HF, cognitive function and guideline-recommended HF medications. Eligible studies were randomized controlled trials (RCT) or cohort studies assessing cognitive function in adult HF patients. Results: Three cohort studies on ACEi/ARBs (N = 5080; 2 prospective, 1 retrospective) reported no significant impact on cognitive function to higher cognitive scores with ACEi/ARBs. Eight studies on sacubitril/valsartan (ARNI, N = 42,143; all observational studies or post-hoc analyses of RCT) found either no effect on cognitive function or reduced risk of new-onset dementia and improved cognitive outcomes with ARNI. Beta-blockers (N = 40; 1 RCT) lacked significant cognitive effects; empagliflozin (SGLT2i, N = 162; 1 prospective) improved cognitive performance in patients with diabetes and HF with preserved ejection fraction; digoxin (N = 1172; 1 retrospective) was associated with enhanced cognitive function; and statins (N = 112,357; 2 retrospective), which are indicated in HF of ischemic aetiology, were not associated with a significant effect on cognition. Conclusions: Guideline-recommended HF medication classes appear to have neutral effects on cognitive function, and some may even offer cognitive benefits. However, the limited number and mostly observational nature of studies prevent firm conclusions. Further research is necessary to better understand the cognitive impact of HF medications.