When to withhold HMG-CoA reductase inhibitors (statins) in inpatients?

From the Guidelines

Statins should be held in hospitalized patients when there are signs of acute liver injury (AST/ALT >3 times upper limit of normal), acute kidney injury, rhabdomyolysis (CK >10 times upper limit of normal), or severe myopathy/myalgia, as recommended by the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1. When considering holding statins in hospitalized patients, several factors should be taken into account, including:

• Acute liver injury, as indicated by elevated liver enzymes (AST/ALT >3 times upper limit of normal) 1
• Acute kidney injury, which may increase the risk of statin-induced myopathy 1
• Rhabdomyolysis, characterized by CK levels >10 times upper limit of normal, which is a contraindication to statin therapy 1
• Severe myopathy or myalgia, which may be a sign of statin-induced muscle damage 1 Additionally, consider holding statins during acute illness with sepsis, hypotension requiring vasopressors, or when starting medications with significant interaction potential like azole antifungals, macrolide antibiotics, or cyclosporine, as these conditions may increase the risk of statin-induced adverse effects 1. For patients undergoing major surgery, statins can typically be continued perioperatively but may need to be held if the patient cannot take oral medications or develops organ dysfunction, as recommended by the 2011 ACCF/AHA guideline for coronary artery bypass graft surgery 1. Resume statins once the acute condition resolves and laboratory values normalize, and monitor liver enzymes, kidney function, and CK levels when restarting statins after holding them, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. The rationale for holding statins during these conditions is to prevent exacerbation of organ injury, as statins are metabolized by the liver and can cause muscle damage, particularly when combined with certain medications or in the setting of compromised organ function 1. It is also important to note that discontinuation of statin or other dyslipidemic therapy is not recommended before or after CABG in patients without adverse reactions to therapy, as stated in the 2011 ACCF/AHA guideline for coronary artery bypass graft surgery 1. In patients with increased diabetes mellitus risk or new-onset diabetes mellitus, it is recommended to continue statin therapy, with added emphasis on adherence, net clinical benefit, and the core principles of regular moderate-intensity physical activity, maintaining a healthy dietary pattern, and sustaining modest weight loss, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. In patients treated with statins, it is recommended to measure creatine kinase levels in individuals with severe statin-associated muscle symptoms, objective muscle weakness, and to measure liver transaminases (aspartate aminotransferase, alanine aminotransferase) as well as total bilirubin and alkaline phosphatase (hepatic panel) if there are symptoms suggesting hepatotoxicity, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. In patients at increased ASCVD risk with chronic, stable liver disease (including non-alcoholic fatty liver disease) when appropriately indicated, it is reasonable to use statins after obtaining baseline measurements and determining a schedule of monitoring and safety checks, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. In patients at increased ASCVD risk with severe statin-associated muscle symptoms or recurrent statin-associated muscle symptoms despite appropriate statin rechallenge, it is reasonable to use RCT proven nonstatin therapy that is likely to provide net clinical benefit, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. Coenzyme Q10 is not recommended for routine use in patients treated with statins or for the treatment of SAMS, 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. Routine measurements of creatine kinase and transaminase levels are not useful in patients treated with statins, 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. The 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation recommend that statins are used in all NSTE-ACS patients, with the aim of reducing LDL-C by at least 50% from baseline and/or achieving LDL-C <1.4 mmol/L (<55 mg/dL) 1. In patients with LVEF <40%, ACE inhibitors (or ARB in cases of intolerance) are recommended in NSTE-ACS patients with co-existing hypertension, LVEF <40%, diabetes, or CKD, unless contraindicated, as recommended by the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1. Beta-blockers are recommended in patients with systolic LV dysfunction or heart failure with reduced LVEF (<40%), as recommended by the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1. The proportion of patients discharged from hospital on high-intensity statins (defined as atorvastatin >40 mg or rosuvastatin >20 mg) unless contraindicated is a key quality indicator, as recommended by the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1. The proportion of patients with LVEF <40% who are discharged from hospital on ACE inhibitor (or ARB if intolerant to ACE inhibitors) is another key quality indicator, as recommended by the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1. The proportion of patients with LVEF <40% who are discharged from hospital on beta-blockers is also a key quality indicator, as recommended by the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1. In summary, statins should be held in hospitalized patients with acute liver injury, acute kidney injury, rhabdomyolysis, or severe myopathy/myalgia, and considered in patients with acute illness, sepsis, hypotension, or significant medication interactions, and resumed once the acute condition resolves and laboratory values normalize, with monitoring of liver enzymes, kidney function, and CK levels, as recommended by the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1, the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1, and the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1.

From the FDA Drug Label

Temporarily discontinue simvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis, e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.

Hold statins inpatient in the following situations:

• Acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis, such as:
  • Sepsis
  • Shock
  • Severe hypovolemia
  • Major surgery
  • Trauma
  • Severe metabolic, endocrine, or electrolyte disorders
  • Uncontrolled epilepsy 2

From the Research

Holding Statins in Inpatient Settings

When considering holding statins in inpatient settings, several factors come into play, including the patient's current health status, potential side effects of statins, and the risk of cardiovascular events.

• Liver Injury: Statins have been associated with liver injury, although this is relatively rare 3, 4. The risk of liver injury may be higher with certain statins, such as atorvastatin, and in patients with pre-existing liver disease.
• Elevated Liver Enzymes: Patients with mildly to moderately elevated baseline liver enzyme levels may still benefit from statin therapy, and the cardiovascular benefits may outweigh the risks 5.
• Side Effects: Statins can cause a range of side effects, including myopathy, transaminase elevations, and an increased risk of incident diabetes mellitus 6.
• Management Strategies: Strategies to minimize statin-related adverse effects include switching to another statin, giving intermittent doses, and adding non-statin agents 6.

Clinical Considerations

In inpatient settings, the decision to hold statins should be made on a case-by-case basis, taking into account the individual patient's risk factors and clinical situation.

• High-Risk Patients: For high-risk patients, the benefits of statin therapy may outweigh the risks, even in the presence of mildly elevated liver enzymes 5.
• Monitoring: Close monitoring of liver enzymes and other potential side effects is essential when initiating or continuing statin therapy in inpatient settings 3, 4.
• Alternative Therapies: In patients who experience severe side effects or liver injury, alternative lipid-lowering therapies may be considered 6.