When is the use of statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) therapy recommended?

From the Guidelines

Statin therapy is recommended for individuals with established atherosclerotic cardiovascular disease (ASCVD), those with significantly elevated LDL cholesterol levels (≥190 mg/dL), adults aged 40-75 with diabetes, and individuals with an elevated 10-year ASCVD risk score (typically ≥7.5%). This recommendation is based on the most recent and highest quality study, which emphasizes the importance of statin therapy in reducing cardiovascular events and mortality 1.

Key Recommendations

• For people with diabetes aged 40–75 years without ASCVD, use moderate-intensity statin therapy in addition to lifestyle therapy 1.
• For people with diabetes aged 40–75 years at higher cardiovascular risk, including those with one or more additional ASCVD risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by ≥50% of baseline and to obtain an LDL cholesterol goal of <70 mg/dL (<1.8 mmol/L) 1.
• Common statins include atorvastatin (10-80 mg daily), rosuvastatin (5-40 mg daily), simvastatin (10-40 mg daily), and pravastatin (10-80 mg daily).

Mechanism of Action

Statin therapy works by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, thereby reducing LDL cholesterol production in the liver and increasing LDL receptor expression, which enhances clearance of LDL from the bloodstream. This mechanism leads to significant reductions in LDL cholesterol (20-60% depending on the statin and dose) and modest increases in HDL cholesterol, ultimately reducing cardiovascular events and mortality.

Monitoring and Side Effects

Patients should be monitored for potential side effects including muscle pain, liver enzyme elevations, and rarely, rhabdomyolysis or new-onset diabetes. Before starting therapy, baseline liver function tests and creatine kinase levels should be checked. Treatment is typically lifelong once initiated.

Additional Considerations

The decision to initiate statin therapy should reflect an assessment of patients’ specific circumstances and their preference for a potential small benefit relative to the potential harms and inconvenience of taking a lifelong daily medication 1. In adults with diabetes aged >75 years already on statin therapy, it is reasonable to continue statin treatment 1.

From the FDA Drug Label

Rosuvastatin tablets are an HMG Co-A reductase inhibitor (statin) indicated: To reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor. As an adjunct to diet to: reduce LDL-C in adults with primary hyperlipidemia. reduce LDL-C and slow the progression of atherosclerosis in adults reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH) As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH). As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia.

The use of statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) therapy is recommended for:

• Primary prevention of major adverse cardiovascular events in adults without established coronary heart disease who are at increased risk of CV disease.
• Treatment of hyperlipidemia, including primary hyperlipidemia, heterozygous familial hypercholesterolemia (HeFH), and homozygous familial hypercholesterolemia (HoFH).
• Treatment of other lipid disorders, including primary dysbetalipoproteinemia and hypertriglyceridemia. 2

From the Research

Use of Statin Therapy

The use of statin therapy is recommended for the management of cholesterol levels and prevention of atherosclerotic cardiovascular disease (ASCVD) [(3,4,5,6,7)].

• Statins represent the first-line therapy for cholesterol management 3.
• The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events 4.
• Statins are the treatment of choice for lowering LDL-C in the majority of patients 5.

Patient Selection for Statin Therapy

The selection of patients for statin therapy depends on their individual risk factors and baseline LDL-C levels [(4,6)].

• Patients at high risk of ASCVD events who require significant LDL-C lowering should be considered for combination therapies comprising statin and nonstatin agents 4.
• The percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels 6.

Combination Therapies with Statins

Combination therapies with statins, such as ezetimibe and PCSK9 inhibitors, can provide additional LDL-C lowering and cardiovascular risk reduction [(3,6,7)].

• A low/moderate-intensity statin combined with ezetimibe yielded a significantly greater reduction in LDL-C levels than high-intensity statin monotherapy 3.
• PCSK9 inhibitors can reduce LDL-C by 50-60% above that achieved by statin therapy alone 7.
• The use of PCSK9 inhibitors is recommended for very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 7.