What are the guidelines for prescribing HMG-CoA reductase inhibitors (statins)?

From the Guidelines

Statin therapy should be initiated with a moderate- to high-intensity statin, with the specific choice and dosage depending on the patient's cardiovascular risk, LDL cholesterol level, and risk of side effects, as recommended by the 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline 1. When initiating statin therapy, it is essential to consider the patient's individual risk factors, such as age, coexisting conditions, and risk factors, to determine the appropriate intensity of statin therapy.

• The primary statins used include atorvastatin (10-80mg daily), rosuvastatin (5-40mg daily), simvastatin (10-40mg daily), and pravastatin (10-80mg daily).
• High-intensity statins (atorvastatin 40-80mg or rosuvastatin 20-40mg) are recommended for those with established cardiovascular disease or very high risk, while moderate-intensity statins are suitable for primary prevention.
• Patients should be monitored with lipid panels and liver function tests at baseline, 4-12 weeks after initiation, and then annually, as outlined in the expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents 2.
• Common side effects include muscle pain, which affects 5-10% of patients, and patients should be advised to report any potential adverse effects, especially muscle cramps, weakness, asthenia, and more diffuse symptoms suggestive of myopathy.
• The 2017 AHA/ACC Clinical Performance and Quality Measures for Adults with ST-Elevation and Non-ST-Elevation Myocardial Infarction also recommend high-intensity statin therapy for patients with clinical atherosclerotic cardiovascular disease, unless contraindicated 3, 4.

From the FDA Drug Label

ROSUVASTATIN tablets, for oral use ... INDICATIONS AND USAGE Rosuvastatin tablets are an HMG Co-A reductase inhibitor (statin) indicated: To reduce the risk of major adverse cardiovascular (CV) events As an adjunct to diet to: reduce LDL-C in adults with primary hyperlipidemia. ... DOSAGE AND ADMINISTRATION Take orally with or without food, at any time of day. Adults:Recommended dosage range is 5 mg to 40 mg once daily.

The guidelines for a statin, specifically rosuvastatin, are to:

• Reduce the risk of major adverse cardiovascular events in adults without established coronary heart disease who are at increased risk of CV disease
• Reduce LDL-C in adults with primary hyperlipidemia as an adjunct to diet
• The recommended dosage range for adults is 5 mg to 40 mg once daily 5
• Key considerations include:
  • Dosage: 5 mg to 40 mg once daily for adults
  • Administration: Take orally with or without food, at any time of day
  • Monitoring: Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating rosuvastatin tablets, and adjust dosage if necessary

From the Research

Guidelines for Statin Therapy

• Statins are a major moderator of hepatic LDL cholesterol output, effectively reducing serum LDL cholesterol concentrations, in a dose-dependent manner 6
• Their use as a single agent or in combination with other treatment modalities (ezetimibe, PCSK9 inhibitors etc.) has been proven to prevent ASCVD events and reduce cardiovascular disease incidence and mortality substantially 6
• Statin therapies are the mainstay of therapy for ASCVD risk reduction and should be initiated in all patients at high enough of a risk, to reduce event rates, morbidity and mortality 6

Patient Selection for Statin Therapy

• Statins are warranted as a first line agent in all secondary prevention patients, as well as those in primary prevention at high or very high risk for ASCVD events 6
• Their use is also based on the presence of specific modifiers, even in selected cases at moderate ASCVD risk 6
• The 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias include the use of PCSK9 inhibitors to very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 7

Combination Therapy with Statins

• Combination lipid-lowering therapy (LLT) with a potent statin (e.g. rosuvastatin) and ezetimibe is often required for high- and very high-risk patients 8
• Single pill combinations (SPCs) improve adherence to treatment as well as the achievement of therapeutic goals and allow a greater reduction in cardiovascular incidents and mortality 8
• PCSK9 inhibitors, evolocumab and alirocumab, are monoclonal antibodies that inactivate the liver proprotein convertase subtilisin kexin 9 (PCSK9) and can reduce LDL-C by 50-60% above that achieved by statin therapy alone 7

Safety and Efficacy of Statin Therapy

• Statins as a class showed statistically significant risk reductions on non-fatal MI, CVD mortality, all-cause mortality, non-fatal stroke, unstable angina, and composite major cardiovascular events 9
• However, statins increased statistically significantly relative and absolute risks of myopathy, renal dysfunction, and hepatic dysfunction 9
• The benefit-harm profile differed by statin type, with atorvastatin and rosuvastatin being most effective in reducing CVD events, while atorvastatin appeared to have the best safety profile 9
• Overwhelming evidence suggests that the benefits of statin therapy far outweigh any real or perceived risks 10