The hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are the most potent, best tolerated and most widely used cholesterol lowering agents and represent some of the most commonly prescribed medications in the United States. HMG-CoA reductase is the rate limiting step in cholesterol synthesis by the liver, and inhibition of its activity causes a significant decrease in total and LDL cholesterol levels. The statins also have minor effects on triglyceride and HDL levels. Seven statins are available in the United States (year of approval and brand name in parentheses): lovastatin (1987: Mevacor), pravastatin (1991: Pravachol), simvastatin (1991: Zocor), fluvastatin (1993: Lescol), atorvastatin (1996: Lipitor), rosuvastatin (2003: Crestor) and pitavastatin (2009: Livalo). All of the statins have been associated with mild-to-moderate serum aminotransferase elevations during therapy that are typically transient, asymptomatic and may resolve even with continuation without dose adjustment. All have also been associated rare instances of clinically apparent acute liver injury. Cases with autoimmune features have been reported with atorvastatin, simvastatin, rosuvastatin and fluvastatin, as well as with combinations of these agents with ezetimibe. The following medications are discussed individually:
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Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 2010; 340: c2197. PubMed Citation (Among 225,922 new users of statins followed in a large UK healthcare database, the risk of moderate-to-severe liver dysfunction [ALT >3 times ULN] was increased in statin users compared to controls, relative risk ranging from 1.31-2.53 in women and 1.21-1.97 in men being highest with fluvastatin and lowest with pravastatin, more common with higher doses and usually arising within 6 months of starting).
Russo MW, Scobey M, Bonkovsky HL. Drug-induced liver injury associated with statins. Semin Liver Dis 2009; 29: 412-22. PubMed PubMed Citation (Review of statin hepatotoxicity and the several forms of liver injury that they can cause, including silent aminotransferase elevations, cholestatic and hepatocellular hepatitis and autoimmune hepatitis-like syndromes, all of which are rare).
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drug induced liver injury including 2 due to atorvastatin, 2 simvastatin and 2
cerivastatin, but none to other statins).
Björnsson E, Jacobsen EI, Kalaitzakis E. Hepatotoxicity associated with statins: reports of idiosyncratic liver injury post-marketing. J Hepatol 2012; 56:374-80. PubMed Citation (Between 1988 and 2010, the Swedish registry received 217 adverse event reports possibly related to statins, 124 [57%] being liver related, 73 of which could be evaluated; 2 were fatal and one led to liver transplant; 3 had positive rechallenge; 43 [59%] were hepatocellular, 22 [30%] cholestatic, and 8 [11%] mixed; 30 were due to atorvastatin, 28 simvastatin, 11 fluvastatin, 2 pravastatin and 2 rosuvastatin, arising after 30 to 248 days).