Abstract Body (Do not enter title and authors here): Introduction: Guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) remains underprescribed despite overwhelming evidence of clinical benefit. Electronic health record (EHR)-based clinical decision support (CDS) tools provide healthcare providers with evidence-based recommendations and reminders within the electronic health record system. EHR-based CDS tools offer an innovative and economical strategy to enhance GDMT prescription rates.

Hypothesis: We hypothesized that EHR-based CDS is associated with increased GDMT initiation or dosage intensification in patients with HFrEF.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) published from inception to May 2024 on four databases: PubMed, Embase, CENTRAL, and MEDLINE. We included RCTs that assessed the impact of EHR-based CDS on GDMT initiation or dosage increase in patients with HFrEF. The primary outcome was a composite of GDMT initiation or dosage increase. Random effects meta-analysis was performed by Review Manager version 5.4 software. I² statistics was used to assess heterogeneity.

Results: Out of 6716 retrieved studies, 5 RCTs involving 4881 patients met inclusion criteria. The inter-rater agreement was excellent (κ = 0.911). The primary outcome showed an overall effect size of 1.38 (95% CI: 1.00-1.91, P = 0.05; I²= 86%). Adjusted relative risk was not reported for most studies, and hence this data could not be provided. Visual inspection of the funnel plot was balanced.

Conclusions: This meta-analysis indicates that EHR-based CDS tools show a potential to increase initiation of GDMT or increase GDMT dosage in HFrEF patients. Further investigation is required to validate these findings due to significant heterogeneity and limited included studies.