What are the 2 injectable medications used to lower Low-Density Lipoprotein (LDL) cholesterol levels?

Injectable Medications for LDL Cholesterol Reduction

The two injectable medications used to lower LDL cholesterol are alirocumab (Praluent) and evolocumab (Repatha), which are PCSK9 inhibitors administered via subcutaneous injection. 1

Mechanism of Action and Efficacy

PCSK9 inhibitors work by binding to PCSK9 protein, which increases the number of LDL receptors available to clear circulating LDL cholesterol from the bloodstream. These medications are highly effective at reducing LDL-C levels:

• Alirocumab: Reduces LDL-C by 45-58% when added to maximally tolerated statin therapy 1
• Evolocumab: Reduces LDL-C by 58-64% when added to maximally tolerated statin therapy 1, 2

Both medications have demonstrated significant clinical benefits beyond just lipid lowering:

• Evolocumab has been shown to reduce the risk of major adverse cardiovascular events (CV death, myocardial infarction, stroke, coronary revascularization) in adults with established cardiovascular disease 2
• Alirocumab reduces the risk of MI, stroke, and unstable angina requiring hospitalization in adults with ASCVD 1

Dosing Regimens

Alirocumab:

• Initial dose: 75 mg subcutaneously every 2 weeks
• Can be increased to 150 mg every 2 weeks if additional LDL-C reduction is needed
• Alternative dosing: 300 mg every 4 weeks (administered as two 150 mg injections) 1

Evolocumab:

• 140 mg subcutaneously every 2 weeks OR
• 420 mg subcutaneously once monthly
• For HoFH patients: 420 mg once monthly, can be increased to 420 mg every 2 weeks if needed after 12 weeks 1, 2

FDA-Approved Indications

Both medications are approved for:

• Adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) as adjunct to diet, either alone or with other lipid-lowering therapies 1

Specific additional indications:

• Alirocumab: Reducing risk of MI, stroke, and unstable angina requiring hospitalization in adults with ASCVD; reducing LDL-C in adults with HoFH 1
• Evolocumab: Reducing risk of MI, stroke, and coronary revascularization in adults with ASCVD; reducing LDL-C in pediatric patients (≥10 years) with HeFH; reducing LDL-C in adults and pediatric patients (≥10 years) with HoFH 1, 2

Safety Profile

Both medications are generally well-tolerated with similar adverse effect profiles:

• Common adverse effects: Nasopharyngitis, injection site reactions, influenza-like symptoms 1
• No significant increase in cognitive adverse effects observed in clinical trials 1
• No clinically significant drug-drug interactions identified 1

Clinical Considerations

• PCSK9 inhibitors represent a significant advancement for patients who cannot achieve adequate LDL-C reduction with statins alone or who are statin-intolerant 1
• These medications can help patients with severe hypercholesterolemia achieve LDL-C goals that were previously unattainable 1
• Both medications have demonstrated LDL-C reductions of 50-60% above what can be achieved with statin therapy alone 3
• Post-commercialization studies have confirmed the efficacy seen in clinical trials, with both medications reducing LDL-C by approximately 63% in real-world settings 4

Important Caveats

• These medications require subcutaneous administration, which may affect patient adherence
• Cost considerations may limit accessibility for some patients
• Prior authorization processes may be burdensome 1
• Patients should be monitored for hypersensitivity reactions, though these are rare 1

PCSK9 inhibitors represent a major advancement in lipid management, particularly for high-risk patients who cannot achieve adequate LDL-C reduction with oral therapies alone.