What is the comparative efficacy and safety of Evolocumab (Repatha) versus Alirocumab (Praluent) for the treatment of hyperlipidemia?

From the Guidelines

Based on the most recent and highest quality evidence, I strongly recommend adding both evolocumab and alirocumab to the hospital formulary, with evolocumab as the primary PCSK9 inhibitor and alirocumab as an alternative option, as both medications demonstrate comparable efficacy in reducing LDL cholesterol and cardiovascular outcomes, with similar safety profiles 1.

Key Considerations

• Both evolocumab and alirocumab are effective in reducing LDL cholesterol by 50-60% and improving cardiovascular outcomes, with similar safety profiles 1.
• The choice between these agents should be determined by patient-specific factors, including dosing preference, insurance coverage, and individual response, rather than meaningful clinical differences in efficacy or safety.
• Evolocumab offers more convenient monthly dosing options and its autoinjector may be easier for some patients to use, while alirocumab provides more flexible dosing with its 75mg starting dose that can be titrated if needed.

Efficacy and Safety

• The FOURIER trial demonstrated that evolocumab reduced the primary endpoint of cardiovascular death, myocardial infarction, and stroke by 20% compared to placebo, with a median follow-up of 2.2 years 1.
• The ODYSSEY OUTCOMES trial showed that alirocumab reduced all-cause death by 22% compared to placebo, with a median follow-up of 2.8 years 1.
• Both trials demonstrated similar safety profiles, with no significant differences in adverse events, including muscle-related events, liver function tests, and neurocognitive events.

Practical Considerations

• Cost considerations and insurance coverage vary significantly between institutions and patients, so having both medications available allows for individualized treatment decisions.
• Both drugs are indicated for patients with established atherosclerotic cardiovascular disease or familial hypercholesterolemia who require additional LDL lowering beyond maximally tolerated statin therapy.
• The key differences between evolocumab and alirocumab are practical, with evolocumab offering more convenient monthly dosing options and alirocumab providing more flexible dosing with its 75mg starting dose that can be titrated if needed.

From the Research

Head-to-Head Comparison of Evolocumab and Alirocumab

• Both evolocumab and alirocumab are proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors used to reduce plasma low-density lipoprotein cholesterol (LDL-C) and the risk of atherosclerotic cardiovascular disease in high-risk patients 2, 3.
• A real-world study comparing the lipid-lowering effects of alirocumab and evolocumab found similar LDL-C lowering effects between the two treatments, with a percentage reduction of -47.0% ± 45.0% for alirocumab and -49.8 ± 24.9% for evolocumab 2.
• Another study evaluating the efficacy and safety of evolocumab and alirocumab in reducing lipids and cardiovascular events suggested that both treatments may reduce cardiovascular outcomes, but large clinical outcome trials are needed to clarify safety concerns and cardiovascular benefits 3.

Efficacy in Reducing LDL-Cholesterol Levels

• Alirocumab and evolocumab have been shown to significantly decrease serum LDL cholesterol levels and reduce the risk of atherosclerotic cardiovascular disease (ASCVD) when added to maximally tolerated statin therapy 4, 5.
• A systematic review of 838 articles found that alirocumab and evolocumab were efficacious in decreasing LDL-C levels and achieving pre-defined LDL-C goals in patients with familial hypercholesterolemia 5.
• The efficacy of alirocumab and evolocumab in reducing LDL-C levels can be influenced by several factors, including sample size, genetic structure, length of trial, and baseline lipid-lowering therapy used 5.

Safety and Tolerability

• PCSK9 inhibitors, including alirocumab and evolocumab, have been associated with adverse events such as injection site reactions 4.
• However, ezetimibe, a cholesterol absorption inhibitor, and bempedoic acid, a hepatic cholesterol synthesis inhibitor, have been shown to have benign side-effect profiles and are generally well tolerated when used in combination with PCSK9 inhibitors 6.
• The use of alirocumab and evolocumab should be considered on a case-by-case basis, taking into account the individual patient's risk factors, medical history, and potential benefits and risks of treatment 3, 6.

Recommendation

• Based on the available evidence, alirocumab and evolocumab appear to have similar efficacy in reducing LDL-C levels and cardiovascular risk 2, 5.
• The choice between alirocumab and evolocumab should be based on individual patient factors, such as medical history, potential drug interactions, and cost considerations 3, 6.
• Further research is needed to fully understand the long-term effects and potential benefits of alirocumab and evolocumab in reducing cardiovascular risk and improving patient outcomes 3, 5.