MAGGIC risk score and drug-related adverse events of sacubitril/valsartan: Insights from the REVIEW-HF registry.

Background: Although the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score is a validated mortality risk tool in heart failure (HF), its utility in assessing drug-related adverse events (DAEs) associated with sacubitril/valsartan initiation remains unclear. This study evaluated the association between the MAGGIC risk score and DAEs related to sacubitril/valsartan initiation in a Japanese multicenter cohort. Methods: We analyzed 787 patients with HF initiated on sacubitril/valsartan 100 mg/day between August 2020 and August 2021. Patients were stratified into tertiles based on MAGGIC risk scores. The primary outcome was DAEs within 90 days of initiation, defined as hypotension, hyperkalemia, renal events, or angioedema. Secondary outcomes included drug discontinuation and clinical outcomes. Results: DAEs occurred in 22.7 % patients. Higher MAGGIC risk scores were significantly associated with increased DAEs (adjusted odds ratio [OR] for highest vs. lowest tertile: 2.64, 95 % confidence interval [CI]: 1.66-4.25, p for trend < 0.001) and sacubitril/valsartan discontinuation (21.3 % of patients; adjusted OR for highest vs. lowest tertile: 2.68, 95 % CI: 1.69-4.32, p for trend < 0.001). Time-dependent Cox proportional hazard analyses revealed that the association between DAEs and clinical outcomes varied across the MAGGIC risk score tertiles, with significant interactions between the composite outcome and hospitalization for HF, particularly in lower-risk groups. Conclusions: The MAGGIC risk score was associated with DAEs risk following sacubitril/valsartan initiation in patients with HF. The impact of DAEs on outcomes varied across risk tertiles, suggesting potential utility for risk stratification and monitoring approaches in HF management.