Abstract 4163: Higher Dose Exposure of Lovastatin is Not Associated with Adverse Hepatic Outcomes in Patients with Existing Liver Disease
OBJECTIVE: We have previously shown that the rate of subjects developing adverse liver outcomes was substantially lower during lovastatin-exposed periods compared to non-exposed periods in patients with pre-existing liver disease. The objective of this analysis was to estimate the dose-response relationship between differing levels of lovastatin exposure and adverse hepatic outcomes.
METHODS: This was a retrospective cohort study. Eligible subjects were adult members of Northern California Kaiser Permanente with at least 2-fold ALT or AST elevations 6–18 months apart, evidence of chronic hepatitis B or C infection, or a diagnosis of a chronic liver disease. Outcomes included the composite of events as well as individual components:
liver injury, defined as moderate (3X ULN<ALT<10X ULN) or severe (ALT<10X ULN);
development of clinical cirrhosis;
The dose-response relationships were analyzed by estimating the risk of each outcome in subgroups defined by quartiles of total cumulative lovastatin exposure. Each of these risks was compared to that in the lovastatin-unexposed reference group and a test for trend applied, using orthogonal polynomial contrasts on the coefficients of categorical levels of the exposure variable.
RESULTS: 93,106 eligible patients were identified, of whom 15% had been exposed to lovastatin. A strong and monotonic dose-response relationship was found for the composite outcome and moderate liver-injury endpoints. For the composite endpoint, hazard ratios declined from 0.81 in the quartile with least lovastatin exposure to 0.44 in the highest exposed group (p<.00001). Similarly, for the moderate liver-injury endpoint, hazard ratios declined from 0.97 to 0.27 with increasing lovastatin exposure (p<.00001).
CONCLUSIONS: Among patients with liver disease, lovastatin exposure was associated with a dose-dependent reduction in the risk of several liver-disease outcomes. These results do not support labeling recommendations for avoiding the use of lovastatin at higher doses in patients with liver disease nor the need to closely monitor LFTs during lovastatin treatment.