AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Understanding Statin Intolerance in the Real World: A Systematic Review and Meta-Analysis of Burden and Treatment Modification
By Shapiro MD, Watanabe A, Nayak D et al.
Background: Elevated LDL-C is a major causal driver of ASCVD. Statins remain the foundation of lipid-lowering therapy (LLT) but intolerance may limit adherence, persistence, dose intensity, and use of adjunctive therapies in clinical practice. Despite its clinical importance, real-world evidence on statin intolerance remains fragmented. This study aimed to systematically characterize reported rates of statin intolerance and related treatment modification in in real-world practice. Research Question: What proportion of statin users are reported to have statin intolerance or intolerance-related treatment modification in real-world observational studies? Methods: EMBASE and MEDLINE were searched for English-language observational studies published from January 2015 to September 2025 that included at least 1,000 adults using statins and reported rates of statin intolerance, statin-associated adverse events, or intolerance -related LLT modification. Two reviewers independently screened all records in accordance with PRISMA guidelines. Random-effects meta-analyses were conducted to estimate pooled rates by outcome definition. Results: Of 3,230 records screened, 101 publications representing 95 unique studies met inclusion criteria. Of these, 27 reported sufficiently comparable outcome definitions and extractable data for inclusion in meta-analysis (Figure 1). Reported rates varied substantially across populations, geographic regions, statin dose and intensity, study designs, and operational definitions of statin intolerance, limiting the interpretability of pooled estimates (Table 1). Among statin users, LLT modification, defined as use of at least two statins with discontinuation or switch to non-statin therapy, was reported in 0.02% - 15.74% of patients across eligible studies. Lipid-lowering therapy modification or statin-associated adverse events were reported in 3.19% - 15.50%. More objective manifestations were reported less often and yielded narrower estimates, including muscle symptoms in 0.42% - 4.03%, liver enzyme abnormalities or liver-related disorders in 0.27% - 3.70%, and new-onset diabetes in 1.30% - 8.17%. Conclusion: Real-world estimates of statin intolerance vary widely because of heterogeneity in populations, statin dosing, study design, and outcome definitions. Statin intolerance is best understood as a spectrum that may include symptoms, laboratory abnormalities, dose reduction, discontinuation, rechallenge failure, and transition to non-statin LLT. However, most real-world studies capture only selected components of this spectrum. Standardized and comprehensive definitions are needed to improve estimation, support cross-study comparability, and better identify patients who require tailored lipid-lowering strategies to optimize LDL-C reduction and reduce ASCVD risk.