S257 Comparative Outcomes of High-Intensity Hydrophilic vs Lipophilic Statins in Patients With Primary Biliary Cholangitis: A Real-World Global Analysis

Introduction: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction and impaired lipid absorption. The pathophysiology may influence the bioavailability and efficacy of hydrophilic vs lipophilic statins, particularly given their varying solubility and pharmacokinetic profiles. It remains unclear whether these differences translate to different clinical outcomes in patients with PBC. Despite the known cardiovascular risks of dyslipidemia, statin use in PBC remains underutilized due to longstanding concerns over hepatotoxicity. Evaluating the comparative safety and effectiveness of statin classes in this unique population is crucial. Methods: We conducted a retrospective analysis using the TriNetX global research network. Adult patients with a diagnosis of PBC were included if they were prescribed a high-intensity hydrophilic statin (e.g., rosuvastatin) or a high-intensity lipophilic statin (e.g., atorvastatin). Patients were propensity-score matched (1:1) on demographics and comorbidities. Primary outcomes included major adverse cardiovascular events, all-cause mortality, and liver-related outcomes (cirrhosis, ascites, hepatic encephalopathy, varices, hepatocellular carcinoma, paracentesis). Secondary outcomes included hospitalizations and quality-of-life markers (i.e., fatigue, pruritus, depression). Results: After matching, 719 patients per patient group were included in the analysis. There were no significant differences in the incidence of major adverse cardiovascular events (39.2% high-intensity hydrophilic vs 42.7% high-intensity lipophilic; hazard ratio (HR) = 0.87 [95% CI: 0.74–1.02], P = 0.18) or all-cause mortality (11.7% high-intensity hydrophilic vs 12.0% high-intensity lipophilic; HR = 0.96 [95% CI: 0.71–1.30], P = 0.87]). Liver outcomes (i.e., cirrhosis, ascites, SBP, hepatic encephalopathy, varices, hepatocellular carcinoma) and symptom burden (i.e., fatigue, pruritus, depression) were similar between both groups (all P-values > 0.05). However, the incidence of all-cause hospitalizations was significantly lower in the hydrophilic statin group (27.4% vs 38.1%; HR = 0.66 [95% CI: 0.55–0.79], P < 0.001]). Conclusion: In this large real-world study of patients with PBC, high-intensity hydrophilic statins were associated with a significantly lower rate of all-cause hospitalizations, with no increase in liver-related and cardiac complications or mortality compared to lipophilic statins. These findings suggest that hydrophilic statins may offer a more favorable safety profile in PBC patients.