A hierarchical risk assessment framework for head-to-head comparison of statin safety profiles in Chinese patients

Ethnic variations in lifestyle, diet, and pharmacogenetics significantly influence statin tolerance. Extending our previous work that documented overall ADR incidence, this study introduces a Hierarchical Risk Assessment Framework (HRAF) to systematically compare statin safety profiles through multi-layered statistical analysis and network visualization. We conducted a post-hoc pooled analysis of Chinese clinical trials (1992–2023) involving seven statins. Our triple-analytical HRAF comprised: (1) global 2 × 7 contingency analysis using Chi-squared tests; (2) individual statin risk profiling with Bonferroni-corrected pairwise comparisons against aggregate controls; and (3) comprehensive pairwise comparisons with Tukey adjustment and network visualization. Muscle-related (189 study units; n = 31,763) and liver-related (188 study units; n = 31,281) adverse drug reactions were analyzed. Applying the HRAF consistently revealed distinct statin-specific safety hierarchies. Global tests confirmed significant class heterogeneity (both p < 0.001). Individual profiling identified atorvastatin with elevated myopathy risk (1.78%; Bonferroni p < 0.001) and pitavastatin with pronounced hepatotoxicity (5.36%; Bonferroni p < 0.001) alongside significant myopathy risk (2.53%; Bonferroni p = 0.002). Pairwise comparisons established detailed risk gradients: atorvastatin showed higher myopathy risk versus five statins (all Tukey p < 0.001 except pitavastatin), while pitavastatin demonstrated superior hepatotoxicity risk versus all comparators (all Tukey p < 0.001) and significant myopathy risk versus multiple statins. Network analysis visually confirmed these high-risk statins as central nodes with multiple significant connections for both ADR types. Using this proposed HRAF provides robust, quantitative safety data for statins in Chinese patients, supporting risk-stratified prescribing that pitavastatin warrants heightened caution regarding liver function, while atorvastatin should be used judiciously in myopathy-susceptible patients. Rosuvastatin and simvastatin emerge as lower-risk alternatives for both outcomes.