Cognitive Safety and Outcomes of Pharmacological Management in Heart Failure: A Systematic Review.

Background/Objectives: Cognitive impairment (CI) is a common complication of heart failure (HF) that undermines self-care, adherence, and outcomes. This systematic review assessed the cognitive effects of pharmacological HF management and related cardiovascular therapies, identifying potential risks and benefits. Methods: Following PRISMA 2020, we searched PubMed, EMBASE, and Scopus for articles published in English between 1 January 2010 and 31 January 2025 (last search 31 January 2025). We included RCTs and cohort studies in adults with HF or high cardiovascular risk that reported cognitive outcomes. Non-pharmacological interventions, studies without relevant cognitive endpoints, and non-original research were excluded. Risk of bias was assessed using RoB 2 for RCTs and the Newcastle-Ottawa Scale for observational studies. Due to heterogeneity in study designs and cognitive measures, results were synthesized qualitatively without meta-analysis. Results: Of 530 records screened, 11 studies encompassing 58,190 participants met the inclusion criteria. Intensive blood pressure (BP) lowering was consistently associated with reduced risk of mild cognitive impairment or dementia compared with standard BP control. In HF populations, sacubitril/valsartan showed no adverse cognitive effects versus other RAAS inhibitors. Across RCTs and observational studies, β-blockers, ACE inhibitors, ARBs, diuretics, and statins showed no evidence of significant cognitive impairment. Comparisons of anticoagulants (dabigatran vs. warfarin; warfarin vs. aspirin) revealed no differences in cognitive trajectories, while optimized medical therapy was associated with parallel improvements in cognitive scores, left ventricular function, and renal parameters. Limitations: Evidence remains constrained by heterogeneity in study design and cognitive assessment tools (often brief screening instruments), inconsistent reporting, and generally short follow-up durations, which may obscure subtle or long-term effects. Conclusions: Contemporary pharmacological therapies for HF appear cognitively safe. Intensive BP control may confer cognitive benefit in high-risk populations, while guideline-directed treatments show no consistent evidence of cognitive harm. Optimized medical therapy may even support cognitive improvement alongside cardiac and renal recovery. Routine cognitive assessment should be integrated into HF care to support individualized management.