Abstract 18079: Among CHD Patients in the IDEAL Study, Those with Elevated Levels of Alanine Aminotransferase at Baseline Had a Lower Rate of Major Coronary Events

Abstract

Background: Previous evidence suggests that statin therapy can reduce cardiovascular (CV) morbidity in patients with mild-to-moderately abnormal liver tests. In this post hoc analysis of the IDEAL study, we investigated the relationship of elevated baseline levels of the liver enzyme alanine aminotransferase (ALT) on CV events, and compared the effects of atorvastatin (ATV) 80 mg versus simvastatin (SIM) 20-40 mg in patients with normal and elevated baseline ALT levels. Methods: IDEAL was a large randomized trial comparing ATV 80 mg with SIM 20-40 mg in 8888 patients with CHD over 4.8 years of follow-up. Cox regression analysis was performed to investigate the relationship of normal levels of ALT (defined as baseline ALT <ULN [upper limit of normal]; 87.8% of subjects) vs elevated ALT (baseline ALT ≥ULN; 11.5% of subjects had ALT ≥ULN-<2 ULN and 0.74% had ALT ≥2 ULN-<3 ULN) on the risk of major coronary events (MCE: CHD death, non-fatal MI or resuscitated cardiac arrest). In addition, treatment effect (ATV 80mg vs SIM 20-40 mg) was examined for subjects with normal and elevated ALT at baseline. Results: Over the course of the study, mean ALT levels increased among patients with normal baseline ALT (n=7782) and decreased for those with ALT ≥ULN at baseline (n=1081). Overall, those patients with normal ALT levels at baseline experienced significantly more MCE than patients with higher baseline ALT levels (≥ULN) (HR=0.76; 95% CI 0.61, 0.96; p=0.02). This finding was consistent in patients treated with ATV (HR=0.60; 95% CI 0.42, 0.87; p=0.007) but not those receiving SIM (p=0.464). In patients with elevated ALT baseline levels, ATV significantly reduced the risk of MCE compared with SIM (HR=0.62; 95% CI 0.40, 0.96; p=0.03), but in patients with normal baseline ALT the difference between treatment groups did not reach statistical significance. Conclusions: In the overall population of CHD patients treated with ATV or SIM, those with normal baseline ALT levels experienced significantly more MCE than those with baseline ALT ≥ULN. The clinical benefits of intensive lipid lowering with ATV compared with a more moderate regimen with SIM were generally greater in patients with abnormal liver tests than in patients with normal liver tests.