Can I start statin (HMG-CoA reductase inhibitor) or other drugs for Peripheral Artery Disease (PAD) in a patient with mildly elevated Liver Function Tests (LFTs)?

Starting Statins in Patients with Mildly Elevated LFTs and PAD

Yes, you should start statin therapy in patients with PAD who have mildly elevated liver function tests—statins are not only safe but strongly recommended in this population, and mild transaminase elevations (<3 times upper limit of normal) are not a contraindication to initiating therapy. 1

Why Statins Are Essential in PAD

Peripheral arterial disease is classified as a very high-risk cardiovascular condition, making lipid-lowering therapy with statins a Class I recommendation (highest level of evidence). 1

• The 2024 ESC guidelines explicitly state that in patients with atherosclerotic peripheral arterial and aortic diseases, lipid-lowering therapy is recommended with the highest level of evidence (Class I, Level A) 1
• Your target LDL-C should be <1.4 mmol/L (55 mg/dL) with a >50% reduction from baseline 1
• If maximally tolerated statins don't achieve this goal, add ezetimibe, and if still not at goal, add a PCSK9 inhibitor 1

Safety of Statins with Elevated LFTs

Patients with NAFLD or NASH are not at higher risk for serious liver injury from statins, and statins can be safely used to treat dyslipidemia in these patients. 1

• The 2018 AASLD guidance explicitly states that statins can be used in patients with NAFLD and NASH, and should only be avoided in decompensated cirrhosis 1
• Asymptomatic transaminase elevations (<3 times ULN) are infrequent and often resolve with dose reduction or rechallenge with alternative statins 1
• Severe statin-associated hepatotoxicity is rare, and routine monitoring of transaminases does not impact clinical outcomes 1

Practical Approach to Initiating Therapy

Obtain baseline liver transaminases before starting statin therapy, then initiate treatment without waiting for normalization if elevations are mild (<3 times ULN). 2

Initial Assessment:

• Measure baseline ALT and AST to identify pre-existing liver conditions 2
• Patients with modest transaminase elevations (<3 times ULN) are NOT contraindicated from starting statins 2
• Rule out other causes of elevated LFTs (alcohol, viral hepatitis, medications) before attributing to potential statin effect 1

Monitoring Strategy:

• Do NOT perform routine periodic monitoring of liver enzymes after starting statins if baseline levels are normal or mildly elevated 1, 2
• Only check LFTs if symptoms of hepatotoxicity develop: unusual fatigue, weakness, loss of appetite, abdominal pain, dark urine, or jaundice 1, 2
• For patients with chronic stable liver disease, establish an appropriate monitoring schedule at baseline 2

If LFTs Rise During Therapy:

• ALT/AST <3 times ULN: Continue statin therapy with follow-up testing 2
• ALT/AST >3 times ULN: Evaluate net benefit, consider dose reduction or alternative statin, but don't automatically discontinue 1, 2
• Persistent significant elevations warrant thorough evaluation for non-statin etiologies 1

Common Pitfalls to Avoid

The biggest mistake is withholding or discontinuing statins due to mild LFT elevations—this denies patients with PAD life-saving therapy based on unfounded concerns. 1, 3

• Multiple studies show that reluctance to prescribe statins in patients with elevated liver enzymes leads to untreated dyslipidemia and increased cardiovascular events 4, 3, 5
• The risk of serious liver injury with statins is extremely rare and did not differ from placebo in clinical trials 2
• Approximately 2% of patients have elevated transaminases after statin initiation, but no data suggest these elevations cause permanent hepatotoxicity 1
• Statins may actually provide additional cardiovascular benefit in patients with abnormal baseline LFTs 3

Statin Selection and Dosing

Start with high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) unless specific contraindications exist, as PAD patients require aggressive LDL-C lowering. 1

• If concerns about hepatic tolerance exist, consider moderate-intensity therapy initially, but recognize this is less effective 1, 2
• Both atorvastatin and rosuvastatin cause dose-dependent borderline LFT elevations that are clinically insignificant 6
• These elevations are almost always <2 times ULN and should not deter prescribing 6

Additional Lipid-Lowering Considerations

If statin intolerance develops (not just mild LFT elevation), use ezetimibe with or without bempedoic acid, and consider PCSK9 inhibitors for high-risk PAD patients not at LDL-C goal. 1

• For PAD patients with triglycerides >1.5 mmol/L despite statin therapy, icosapent ethyl 2g twice daily may be considered (Class IIb) 1
• Fibrates are not recommended for cholesterol lowering 1