From the Guidelines
I strongly recommend maintaining the current rosuvastatin dose of 20mg daily for now and reassessing in 6 weeks rather than increasing the dose before discharge, as the patient's deranged liver function tests (elevated GGT, ALT, and AST) and significant alcohol consumption are concerning factors that may be contributing to liver dysfunction 1. While aggressive lipid management is generally beneficial post-acute coronary syndrome (ACS) in high-risk patients, safety considerations are paramount. Statins can occasionally cause hepatotoxicity, and increasing the dose with pre-existing liver abnormalities could exacerbate liver damage.
The 2019 systematic review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol provides evidence that statin therapy is beneficial in reducing cardiovascular events, but it also highlights the importance of considering the patient's individual risk factors and comorbidities 1. The IMPROVE-IT study, which is one of the studies included in the review, showed that ezetimibe added to simvastatin reduced the risk of cardiovascular events in patients with ACS, but it also noted that the incidence of elevations in ALT >3 ULN was not significantly different between the treatment groups 1.
Given the patient's history of daily alcohol consumption, it is essential to address this issue as it can contribute to liver dysfunction and increase the risk of hepatotoxicity with statin therapy. The patient's weight of 110kg is also relevant, but secondary to addressing the liver concerns first. Rosuvastatin 20mg is already a moderate-intensity dose that provides significant LDL reduction, making it reasonable to observe the response before further intensification.
At the 6-week follow-up, reassess both lipid levels and liver function tests. If LFTs have improved and LDL remains above target, then consider dose escalation. Additionally, reducing alcohol intake is essential for both liver health and cardiovascular risk reduction. The ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction also support the initiation of lipid-lowering therapy before hospital discharge, but emphasize the importance of considering the patient's individual risk factors and comorbidities 1.
In this case, the patient's liver dysfunction and alcohol consumption take precedence, and a more cautious approach is warranted. Maintaining the current dose and reassessing in 6 weeks is the most appropriate course of action, as it allows for monitoring of the patient's liver function and lipid levels while minimizing the risk of hepatotoxicity.
From the FDA Drug Label
Rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis. Chronic alcohol liver disease is known to increase rosuvastatin exposure. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [ see Contraindications (4), Warning and Precautions (5. 3)and Clinical Pharmacology (12.3)].
The patient's history of daily alcohol consumption and elevated liver enzymes (GGT and transaminases) may increase the risk of hepatic injury with rosuvastatin. Considering the patient is already on rosuvastatin 20mg, caution is advised. The FDA drug label recommends careful consideration in patients with a history of liver disease or substantial alcohol consumption.
- Key considerations:
- Patient's liver function tests should be monitored closely.
- The patient's weight and liver function should be taken into account when deciding on aggressive lipid therapy.
- The risk of myopathy and rhabdomyolysis may be increased in patients with renal impairment or those taking certain concomitant medications. Given the potential risks, aggressive lipid therapy should be approached with caution in this patient, and the benefits and risks of continuing or increasing the dose of rosuvastatin should be carefully weighed 2.
From the Research
Patient Considerations
- The patient is at high risk post-acute coronary syndrome (ACS) with elevated liver enzymes, specifically gamma-glutamyl transferase (GGT) and transaminases, and a history of daily alcohol consumption.
- The patient is currently on rosuvastatin (Rosu) 20mg, and the consideration is whether to initiate aggressive lipid therapy.
Current Treatment and Liver Function
- The patient's current treatment with rosuvastatin 20mg may not be sufficient to achieve optimal lipid levels, considering the patient's high-risk status and elevated liver enzymes 3, 4.
- The patient's liver function tests and history of daily alcohol consumption should be taken into account when considering aggressive lipid therapy, as certain lipid-lowering therapies may be contraindicated or require dose adjustments in patients with liver dysfunction.
Alternative Therapies
- Combination therapy with rosuvastatin and ezetimibe may be a viable option for achieving optimal lipid levels in high-risk patients, as it has been shown to be effective in reducing LDL-C levels and improving cardiovascular outcomes 5, 6.
- The addition of bempedoic acid to rosuvastatin and ezetimibe may provide further reductions in LDL-C levels, as demonstrated in the LAI-REACT study 6.
Clinical Practice and Guidelines
- Current guidelines recommend reducing LDL-C levels by ≥50% compared to baseline values with a LDL-C level below 1.4 mmol/l (55 mg/dl) in patients after an ACS 7.
- However, in real-world clinical practice, a low proportion of patients are treated according to recommended lipid-lowering therapies, and very few people reach these targets 7.
- The use of aggressive lipid therapy, including combination therapy with high-intensity statins, ezetimibe, and other lipid-lowering agents, may be necessary to achieve optimal lipid levels and improve cardiovascular outcomes in high-risk patients 3, 4.