Contraindication-adjusted prescription omission patterns of RASi, beta-blockers, and MRAs in hospitalized heart failure: associations with 30-day and 1-year mortality

Guideline directed therapy is still underused in heart failure and little is known about how missing specific medications near discharge relates to survival. The aim of this study is to examine whether study-defined omission patterns of RASi (ACE inhibitors, ARBs, or ARNIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) in the final 48 h before discharge were associated with short-term and 1-year mortality among hospitalized adults with heart failure. Adult admissions with a recorded heart failure diagnosis were identified using ICD-9 and ICD-10 codes. The three classes were RASi, beta-blockers, and MRAs (SGLT2 inhibitors were not included). A contraindication-adjusted operational framework was used to identify admissions without selected laboratory or hemodynamic barriers to these therapies and to classify late-hospital prescription omission patterns. Final-48-h orders were a proxy for treatment near discharge, not a reconciled discharge list. This framework did not establish heart failure phenotype-specific guideline eligibility. Associations with mortality within 30 and 365 days after discharge were evaluated using multivariable regression models. The final analytic cohort included 57,098 admissions from 24,922 patients. The reference group with prescriptions for all three study classes was small whereas omission of 2 or 3 therapies was substantially more common across the cohort. Admissions with prescriptions for all three study classes had the lowest 365-day mortality (13.88%). Crude 365-day mortality was higher in all omission groups, reaching 30.84% when RASi and beta-blocker were omitted and 27.50% when all three classes were omitted. In adjusted analyses, omission of all 3 therapies was associated with higher 30-day mortality (OR = 1.67). For 365-day mortality, the strongest adverse association was observed for omission of renin-angiotensin system inhibitor plus beta-blocker (HR = 1.33). Late-hospital omission patterns involving RASi and omission of all three study therapies were associated with higher post-discharge mortality. As heart failure phenotype and left-ventricular ejection fraction were not incorporated into the eligibility definition, these findings should be interpreted as prognostic associations of prescribing patterns rather than causal effects of withholding guideline-indicated HFrEF therapy.