When to increase HMG-CoA reductase inhibitor (statin) therapy?

From the Guidelines

Statin therapy should be increased when a patient has a less-than-anticipated response to moderate-intensity statin, with <30% reduction in LDL-C, or has high-risk markers, and after addressing statin adherence and lifestyle modifications. This recommendation is based on the 2017 focused update of the ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk 1. The update suggests that if a patient has a less-than-anticipated response to statin therapy, with <30% reduction in LDL-C, or has high-risk markers, additional clinical approaches are warranted, including increasing the statin dose to a high-intensity statin.

Key considerations for increasing statin therapy include:

• LDL cholesterol levels above target (typically >70 mg/dL for high-risk patients or >100 mg/dL for moderate-risk patients) 1
• Presence of high-risk markers, such as family history of premature ASCVD, elevated Lp(a), or evidence of accelerated subclinical atherosclerosis 1
• Patient's 10-year ASCVD risk, with higher risks warranting more intensive therapy 1
• Statin adherence and potential barriers to adherence, which should be addressed before increasing therapy 1

When increasing statin therapy, it is essential to monitor for side effects, such as muscle pain, liver function abnormalities, and new-onset diabetes, particularly in elderly patients or those with multiple medications 1. Allow 4-12 weeks after dose adjustment to reassess lipid levels and determine if further adjustments are needed. The 2018 cholesterol clinical practice guidelines also support the use of high-intensity statin therapy in patients with high-risk markers or those who have not achieved adequate LDL-C reduction with moderate-intensity statin therapy 1.

From the FDA Drug Label

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the atorvastatin dosage.

The decision to increase statin dosage should be made with caution, considering the risk of myopathy and rhabdomyolysis.

• Key factors to consider before increasing statin dosage include:
  • Patient's medical history and current health status
  • Potential drug interactions
  • Patient's ability to tolerate increased dosage
• Monitoring is essential when increasing statin dosage, including:
  • Regular check-ups with the patient's healthcare provider
  • Monitoring of liver enzyme levels and creatine kinase (CK) levels
  • Patient education on recognizing and reporting symptoms of myopathy and rhabdomyolysis 2

From the Research

When to Increase Statin

• The decision to increase statin dosage or intensity should be based on individual patient factors, such as the risk of cardiovascular events and the presence of specific diseases 3.
• For patients who are not achieving their low-density lipoprotein cholesterol (LDL-C) targets on maximally tolerated doses of high-intensity statins, adding a cholesterol absorption inhibitor like ezetimibe may be considered 4.
• The combination of a statin and ezetimibe has been shown to be safe and effective in patients with hypercholesterolemia or dyslipidemia, and can help more patients achieve their LDL-C goals 4, 5, 6.
• The choice of statin and dosage should be individualized based on factors such as efficacy, safety, and potential drug interactions 3.
• For patients with low and moderate risk, a fixed-dose combination of low-intensity rosuvastatin and ezetimibe may be an effective alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management 6.

Factors to Consider

• The risk of new diabetes, chronic kidney disease, liver disease, human immunodeficiency virus infection, organ transplant, heart failure, and elderly people should be taken into account when choosing a statin and dosage 3.
• The pharmacokinetics, safety, drug metabolism, and interactions of different statins should be considered to provide the best choice in different clinical scenarios 3.
• The efficacy and safety of different statin combinations, such as rosuvastatin and ezetimibe, should be evaluated in clinical practice to determine the best treatment approach for individual patients 4, 5, 6.