PATIENTS WITH ELEVATED LIVER ENZYMES ARE NOT AT HIGHER RISK FOR HEPATOTOXICITY FROM LOVASTATIN THAN THOSE WITH NORMAL LIVER ENZYMES

Purpose: It is recommended that lovastatin not be used in patients with unexplained transaminasemia, however, studies evaluating its risk of hepa-totoxicity in subj ects with elevated liver enzymes are lacking. This study was conducted to test the hypothesis that patients with elevated liver enzymes are not at higher risk for lovastatin hepatotoxicity than those with normal liver enzymes. Methods: Our study consisted of the following 3 cohorts of patients seen between 12/87 and 12/98. Cohort 1: 135 patients with elevated baseline enzymes (AST >40 IU/L or ALT >35 IU/L with no evidence of HBV or HCV or alcohol consumption) who received lovastatin, Cohort 2: 620 patients who received lovastatin but did not have elevated liver enzymes, and Cohort 3: 2644 age, gender and race matched patients with elevated liver enzymes (without HCV or HBV or alcohol consumption) who did not receive lovastatin. The effect of lovastatin on livertests was assessed overa 12-month fμ. “Significant elevation in liver biochemistries” was defined as the development of bilirubin >3 mg/dl (regardless of their baseline transaminases) or elevation of AST and/or ALT >5 times ULN in patients with normal enzymes or >5-fold elevation from their baseline AST and/or ALT values in patients with elevated baseline enzymes. We also assessed the proportion of patients who developed AST or ALT >3 ULN and bilirubin >2 ULN during the follow-up (Hy's rule). Results: As shown in the table, during the fμ, AST, ALT or bilirubin values or the frequency of significant elevations in liver biochemistries or Hy's rule were not significantly different between cohorts I and II (p = ns). A greater proportion of patients belonging to cohort III had significant elevations in liver biochemistries or Hy's rule (p <0.01 vs. other 2 cohorts).TableConclusions: Patients with elevated liver enzymes are not at higher risk for lovastatin hepatotoxicity than those with normal liver enzymes.