Does elevated prothrombin time warrant discontinuation of atorvastatin (atorvastatin) in a patient with cirrhosis?

From the Guidelines

A high prothrombin time alone does not necessarily warrant stopping atorvastatin in a patient with cirrhosis. The decision to continue or discontinue atorvastatin should be based on a comprehensive assessment of liver function, not just prothrombin time. According to the most recent guidelines, patients with cirrhosis are in a 'rebalanced' haemostatic state, and a prolonged prothrombin time does not predict bleeding 1. Atorvastatin can generally be continued in patients with stable chronic liver disease, including compensated cirrhosis. However, if there are signs of decompensated cirrhosis or acute liver injury (significantly elevated transaminases >3 times upper limit of normal, worsening synthetic function, or clinical deterioration), then atorvastatin should be temporarily held or discontinued. Regular monitoring of liver function tests is recommended, including ALT, AST, bilirubin, and albumin, along with prothrombin time. The concern with statins in liver disease is the theoretical risk of hepatotoxicity, though evidence suggests statins are generally safe in stable liver disease and may even be beneficial in reducing cardiovascular risk in cirrhotic patients 1. If atorvastatin must be discontinued, consider resuming once liver function stabilizes, potentially at a lower dose (10-20mg daily) with close monitoring. Always balance the cardiovascular benefits against potential hepatic risks when making this decision.

Some key points to consider:

• The coagulation cascade is rebalanced in patients with cirrhosis, resulting in a relative hypercoagulable state 1.
• Standard measures of coagulation, such as INR, serve the practitioner poorly when an accurate assessment of bleeding risk is needed 1.
• Transfusions carry significant risk for immunologic consequences, exacerbate portal hypertension, and are likely overutilized in patients with cirrhosis 1.
• Further study of global measures of coagulation, such as TEG and ROTEM, to determine appropriate cutoffs for therapeutic intervention are urgently needed 1.

In terms of management, the AGA clinical practice guideline on the management of coagulation disorders in patients with cirrhosis recommends against traditional coagulation testing, as it does not accurately predict bleeding risk 1. Viscoelastic tests (VETs) are an attractive alternative to traditional coagulation testing, as they are dynamic tests that measure clot formation, clot strength, and dissolution over time 1. However, more research is needed to determine the appropriate use of VETs in patients with cirrhosis.

Ultimately, the decision to stop atorvastatin in a patient with cirrhosis and a high prothrombin time should be individualized and based on a comprehensive assessment of liver function and cardiovascular risk. The most recent and highest quality study suggests that atorvastatin can be continued in patients with stable chronic liver disease, including compensated cirrhosis, without an increased risk of bleeding 1.

From the FDA Drug Label

5.3 Hepatic Dysfunction Increases in serum transaminases have been reported with use of atorvastatin calcium tablets [see Adverse Reactions (6.1)] . Atorvastatin calcium tablets are contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4) ] If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue atorvastatin calcium tablets.

The information provided does not directly address the relationship between a high prothrombin time and the decision to stop atorvastatin in a patient with cirrhosis. Key points:

• Atorvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis.
• The label does not provide guidance on managing atorvastatin in patients with cirrhosis who develop a high prothrombin time. 2

From the Research

Coagulopathy in Cirrhosis

• Patients with cirrhosis have a complex coagulopathy characterized by both hypocoagulable and hypercoagulable features 3.
• The prothrombin time (PT) and international normalized ratio (INR) are commonly used to assess bleeding risk in cirrhosis, but they have been shown to be inadequate for this purpose 4, 5, 6.
• Studies have demonstrated that patients with cirrhosis have a prothrombotic profile, despite having a prolonged PT/INR 4, 5.

Statin Use in Cirrhosis

• Statins have been shown to have a positive impact on chronic liver disease (CLD) and cirrhosis, with evidence suggesting they reduce mortality, hepatic decompensation, and variceal bleeding 7.
• The use of statins in patients with cirrhosis is not contraindicated, and they may even have beneficial effects on the disease 7.

Atorvastatin and Coagulopathy

• There is no direct evidence to suggest that atorvastatin should be stopped in patients with cirrhosis and a high prothrombin time.
• The decision to stop atorvastatin should be based on the individual patient's risk-benefit profile, taking into account the potential benefits of statin therapy in cirrhosis 7.
• Alternative biomarkers, such as thrombin generation assays, may be more accurate in assessing bleeding risk in patients with cirrhosis 4, 5.