When should statins (HMG-CoA reductase inhibitors) be avoided?

When to Avoid Statins

Statins should be avoided in patients with acute liver failure or decompensated cirrhosis, following hemorrhagic stroke (unless atherosclerotic disease or high CVD risk is present), during pregnancy and breastfeeding, and when concomitant use with cyclosporine or gemfibrozil is necessary. 1, 2

Absolute Contraindications

Active Liver Disease

• Acute liver failure and decompensated cirrhosis are absolute contraindications to statin therapy. 1, 2
• Patients with acute viral or alcoholic hepatitis should not receive statins until aminotransferases normalize. 3
• Advanced or end-stage parenchymal liver disease contraindicates statin use due to severely impaired drug metabolism. 3

Hemorrhagic Stroke

• Statins should be avoided following hemorrhagic stroke unless there is evidence of atherosclerotic disease or high cardiovascular disease risk. 2
• This contrasts with ischemic stroke, where statins are strongly recommended for secondary prevention. 2

Pregnancy and Lactation

• Stop statin therapy 1-2 months before contemplating pregnancy. 2
• Avoid all lipid-lowering drugs when pregnancy is planned, during pregnancy, and during breastfeeding. 2
• For severe familial hypercholesterolemia patients, bile acid sequestrants or LDL-C apheresis may be considered as alternatives. 2

Relative Contraindications and High-Risk Situations

Drug Interactions Requiring Avoidance

• Concomitant use with cyclosporine or gemfibrozil is not recommended. 1, 2
• Exercise extreme caution or avoid statins when patients require: 2
  • Macrolide antibiotics (azithromycin, clarithromycin, erythromycin)
  • Azole antifungals (itraconazole, ketoconazole, fluconazole)
  • HIV protease inhibitors
  • Tacrolimus

Acute Critical Illness

• Temporarily discontinue statins in patients experiencing acute conditions at high risk of developing renal failure secondary to rhabdomyolysis. 1
• This includes: 1
  • Sepsis or shock
  • Severe hypovolemia
  • Major surgery or trauma
  • Severe metabolic, endocrine, or electrolyte disorders
  • Uncontrolled epilepsy

Active Myopathy

• Discontinue statins immediately if markedly elevated creatine kinase levels occur or if myopathy is diagnosed or suspected. 1, 4
• The combination of proximal myopathy, elevated creatine kinase, and skin changes after statin therapy strongly suggests statin-induced myopathy requiring prompt discontinuation. 4
• Immune-mediated necrotizing myopathy (IMNM) requires permanent discontinuation and may necessitate immunosuppressive therapy. 1

Situations Requiring Extreme Caution (Not Absolute Avoidance)

Heart Failure Without Other Indications

• Cholesterol-lowering therapy with statins is not recommended in patients with heart failure in the absence of other indications, though it is not harmful. 2
• Consider moderate-intensity statins only in heart failure patients with ischemic etiology and reasonable life expectancy (3-5 years). 2

Dialysis-Dependent Chronic Kidney Disease

• In patients with dialysis-dependent CKD without atherosclerotic CVD, statins should not be initiated. 2
• However, patients already taking statins who initiate dialysis should continue therapy, especially if they have established ASCVD. 2

Aortic Stenosis Without CAD

• Cholesterol-lowering treatment is not recommended in patients with aortic valvular stenosis without coronary artery disease in the absence of other indications. 2

Important Clinical Caveats

Compensated Liver Disease Is NOT a Contraindication

• Statins should not be withheld from patients with NAFLD, including those with compensated cirrhosis, because hepatotoxicity is very rare and benefits significantly outweigh risks. 2
• Chronic hepatitis patients may be treated with statins if cardiovascular risk is elevated, provided careful follow-up occurs. 3
• Statin-induced hepatotoxicity occurs in only 1-3% of patients, is usually asymptomatic, dose-related, and typically resolves with dose reduction or withdrawal. 3, 5

Elevated Baseline Liver Enzymes

• Patients with transaminase levels no more than three times the upper limit of normal can continue taking statins. 5
• Coexisting elevations from nonalcoholic fatty liver disease and stable hepatitis B and C are not contraindications to statin use. 5

High-Risk Patient Populations Requiring Lower Doses (Not Avoidance)

The following patients should receive statins cautiously at lower doses rather than avoiding them entirely: 2

• Advanced age (especially >80 years), particularly frail elderly women
• Small body frame and frailty
• Multisystem disease (chronic renal insufficiency, especially due to diabetes)
• Perioperative periods