From the Guidelines
Rosuvastatin can be hepatotoxic in some patients, though serious liver damage is rare, and the risk of hepatotoxicity should be weighed against the benefits of statin therapy in reducing morbidity and mortality from cardiovascular disease, as stated in the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.
Background
The use of statins, including rosuvastatin, has been associated with elevations in liver enzymes, typically occurring in about 1-3% of patients, as noted in the ACC/AHA/NHLBI clinical advisory on the use and safety of statins 1. These elevations are usually mild, asymptomatic, and often resolve even with continued therapy. However, patients with pre-existing liver disease, heavy alcohol consumption, or those taking other hepatotoxic medications may be at higher risk for liver complications.
Risk Factors and Monitoring
The mechanism of statin-induced liver injury involves disruption of hepatocyte cell membranes and mitochondrial function. Monitoring liver function tests is recommended before starting therapy and as clinically indicated thereafter, though routine periodic monitoring is no longer universally recommended, as stated in the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.
- Patients with increased risk of liver disease should be closely monitored.
- Symptoms suggesting liver injury, such as fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice, or liver enzymes exceeding 3 times the upper limit of normal, should prompt discontinuation of rosuvastatin.
- Alternative cholesterol-lowering strategies may be needed for patients who cannot tolerate statins due to liver concerns.
Clinical Decision Making
In clinical practice, the decision to use rosuvastatin should be based on the individual patient's risk factors for cardiovascular disease and liver disease, as well as their potential to benefit from statin therapy, as recommended in the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.
- The benefits of statin therapy in reducing morbidity and mortality from cardiovascular disease should be weighed against the risks of hepatotoxicity.
- Patients with pre-existing liver disease or other risk factors for liver disease should be closely monitored for signs of liver injury.
- Alternative cholesterol-lowering strategies should be considered for patients who cannot tolerate statins due to liver concerns.
From the FDA Drug Label
Hepatic Dysfunction Inform patients that rosuvastatin may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions (5. 3)] .
Rosuvastatin may cause hepatotoxicity, as evidenced by liver enzyme elevations and possibly liver failure. Patients should be advised to promptly report symptoms such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. 2
From the Research
Hepatotoxicity of Rosuvastatin
- Rosuvastatin has been reported to cause liver toxicity in some cases, with studies suggesting that it may have a greater potential to damage the liver compared to other statins 3.
- The mechanisms involved in the hepatotoxicity of rosuvastatin are unclear, but its selective and efficient uptake by hepatocytes may play a role 3.
- However, other studies have found that rosuvastatin has the same rate of elevations of hepatic enzymes as other statins, and that it is unlikely to cause significant liver injury 4.
- There have been reports of acute liver injury in patients treated with rosuvastatin, with some cases showing autoimmune features and requiring corticosteroid therapy 5.
- A study comparing atorvastatin and rosuvastatin in patients with acute myocardial infarction and elevated liver enzymes found that atorvastatin was associated with higher all-cause mortality than rosuvastatin 6.
Clinical Evidence
- The safety of rosuvastatin has been evaluated in several studies, with most finding that it is well-tolerated and effective in reducing LDL-C levels 4, 7.
- Rosuvastatin has been shown to have a low potential for CYP3A4 interactions and substantial LDL-C lowering capacity, making it a useful agent in the treatment of cardiovascular disease 7.
- However, the risk of liver-related adverse events with rosuvastatin is still a concern, and patients should be monitored for signs of liver injury 3, 5.