Simvastatin 단독요법과 Ezetimibe/Simvastatin 병용요법의 간 손상 발현 빈도 비교

Abstract

Ezetimibe was approved by the FDA in 2002 and again by the KFDA in 2004 for either in hypercholesterolemia alone or in combination with statins. It was considered to be safer than statins in terms of hepatotoxicity. However, certain cases of serious cholestatic hepatitis and acute immune hepatitis are recently being reported. Also, the incidence of abnormal LFT that significantly elevated more than three times of the upper limits of normal (ULN) is being reported to be 2% with the ezetimibe and simvastatin combination therapy, and there were no reported cases with simvastatin monotherapy in the study published in 2004. Three out of four adverse events being reported in the Drug Safety Monitoring Center of SNUH are associated with liver enzyme elevations and intrahepatic cholestasis. However, the rarely published about ezetimibeinduced hepatic injury and long-term safety studies are still insufficient. This study includes the patients who were administered with either ezetimibe and simvastatin (472) or simvastatin alone (494) between July 2009 and June 2010 at SNUH, and also analyzed the incidence rate of drug-induced liver injury by using LFTs. We defined the liver injury criteria as ALT ≥ 3×ULN, ALP ≥ 2×ULN, or if ALT or ALP is elevated, the total bilirubin (TB) ≥ 3×ULN,and then assessed the incidence according to age, gender, treatment duration, and disease. Data were collected by data-mining processes, retrospectively. We observed significant increases of liver injury in the combination group as compared with the simvastatin group. It thus suggests that ezetimibe and simvastatin combination therapy may have higher rates of liver injury than simvastatin monotherapy, and for this reason, special caution is required when administering ezetimibe.