Abstract TP297: Hepatic Enzyme Elevation Among Patients Receiving Intensive Medical Treatment for High-Grade Intracranial Stenosis

Background: High-dose statin therapy and aggressive blood pressure control in patients with transient ischemic attack (TIA) or non-disabling ischemic stroke from high-grade (70–99%) intracranial arterial stenosis may cause hepatic enzyme elevation, potentially impacting therapy adherence. Methods: Post-hoc analysis of SAMMPRIS trial participants receiving intensive medical therapy (LDL cholesterol target <70 mg/dL; systolic blood pressure <140 mm Hg, <130 mm Hg if diabetic). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at baseline, 1 month, 4 months, and annually. Persistent ALT/AST >3× upper limit of normal (ULN) after repeat testing led to statin discontinuation. Patients were grouped by ≥50% ALT rise (“hepatic dysfunction”) vs. no elevation. Results: Of 401 patients, 149 (37.2%) developed hepatic dysfunction, median onset 30 days (IQR 27–35). Compared with no elevation, affected patients had higher baseline LDL (84.6 vs. 67.1 mg/dL, p <0.01), lower BMI (29.0 vs. 31.5 kg/m2, p <0.01), and less diabetes (33.6% vs. 44.0%, p =0.02). Serum creatinine was similar (1.0 ± 0.3 vs. 1.0 ± 0.3 mg/dL, p =0.78). ALT normalized in 32.2% but remained elevated in 20.1%. Myocardial infarction (MI) risk was higher with hepatic dysfunction (5.4% vs. 1.6%, p =0.03), with no difference in ischemic stroke after 30 days (5.4% vs. 5.6%, p =0.94). Multivariate analysis: hepatic dysfunction independently predicted MI (OR 3.45, 95% CI 1.04–11.49, p =0.04). Conclusions: Hepatic enzyme elevation occurred in over one-third of patients, primarily within the first month, and was linked to increased MI risk. Early laboratory monitoring may be warranted during intensive therapy for high-grade intracranial stenosis.