What injectable medication can be given for primary prevention of Hyperlipidemia (HLD)?

From the Guidelines

For primary prevention of hyperlipidemia (HLD), PCSK9 inhibitors are the main injectable medication option, including evolocumab (Repatha) and alirocumab (Praluent), as recommended by the most recent guidelines 1. These medications are typically administered subcutaneously every 2-4 weeks. Evolocumab is dosed at 140 mg every 2 weeks or 420 mg monthly, while alirocumab is given as 75-150 mg every 2 weeks or 300 mg monthly. The mechanism of action of PCSK9 inhibitors involves preventing the degradation of LDL receptors on liver cells, allowing more receptors to remain active and remove LDL cholesterol from the bloodstream, resulting in significant LDL cholesterol reductions of 50-70% 1. Common side effects include injection site reactions, nasopharyngitis, and upper respiratory tract infections 1. Before starting these medications, patients should have baseline lipid levels measured and should continue lifestyle modifications including heart-healthy diet and regular exercise. Key considerations for prescribing PCSK9 inhibitors include cost, subcutaneous administration, and the potential need for prior authorization 1. It is essential to weigh the benefits and risks of PCSK9 inhibitors in the context of individual patient needs and cardiovascular risk profiles. Some studies suggest that PCSK9 inhibitors may be well-tolerated and effective in both men and women, although more research is needed to fully understand their effects in different populations 1. Overall, PCSK9 inhibitors offer a valuable treatment option for patients with primary hyperlipidemia who require additional LDL cholesterol reduction beyond statin therapy.

Some key points to consider when prescribing PCSK9 inhibitors include:

• Patient selection: Identify patients with high cardiovascular risk who cannot achieve adequate LDL cholesterol reduction with statins or cannot tolerate statins due to side effects.
• Dosing and administration: Follow recommended dosing regimens and administer subcutaneously every 2-4 weeks.
• Monitoring: Regularly monitor lipid levels and adjust treatment as needed to achieve desired LDL cholesterol reductions.
• Lifestyle modifications: Encourage patients to continue heart-healthy diet and regular exercise in conjunction with PCSK9 inhibitor therapy. It is crucial to prioritize the single most recent and highest quality study, which in this case is 1, when making a definitive recommendation for primary prevention of HLD.

From the FDA Drug Label

The results of primary and secondary efficacy endpoints are shown in Table 3 below. REPATHA significantly reduced the risk for the primary composite endpoint (time to first occurrence of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization; p < 0. 0001) and the key secondary composite endpoint (time to first occurrence of cardiovascular death, myocardial infarction, or stroke; p < 0. 0001). Primary Hyperlipidemia Study 2 (LAPLACE-2, NCT01763866) was a multicenter, double-blind, randomized controlled 12-week trial in which patients were initially randomized to an open-label specific statin regimen for a 4-week lipid stabilization period followed by random assignment to subcutaneous injections of REPATHA 140 mg every 2 weeks, REPATHA 420 mg once monthly, or placebo for 12 weeks The difference between REPATHA and placebo in mean percent change in LDL-C from baseline to Week 12 was −71% (95% CI: −74%, −67%; p < 0.0001) and −63% (95% CI: −68%, −57%; p < 0.0001) for the 140 mg every 2 weeks and 420 mg once monthly dosages, respectively.

The injectable medication that can be given for HLD primary prevention is evolocumab (SQ), also known as REPATHA. It is administered via subcutaneous injection, with dosages of 140 mg every 2 weeks or 420 mg once monthly. Evolocumab has been shown to significantly reduce the risk of major cardiovascular events, including cardiovascular death, myocardial infarction, and stroke, in patients with established cardiovascular disease 2. Additionally, it has been demonstrated to effectively lower LDL-C levels in patients with primary hyperlipidemia, with mean percent changes from baseline to Week 12 of −71% and −63% for the 140 mg every 2 weeks and 420 mg once monthly dosages, respectively. Key benefits of evolocumab include:

• Significant reduction in risk of major cardiovascular events
• Effective lowering of LDL-C levels
• Administered via subcutaneous injection, with two available dosages.

From the Research

Injectable Medications for HLD Primary Prevention

• Alirocumab and evolocumab are two injectable medications that can be used for the primary prevention of hyperlipidemia (HLD) 3, 4, 5, 6, 7.
• These medications are proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which have been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with HLD 3, 4, 5, 6, 7.
• Alirocumab has been shown to reduce LDL-C levels by 8-67% in patients with high cardiovascular risk who are not at LDL-C target goals 3.
• Evolocumab has been shown to reduce LDL-C levels by 32-71% in patients with heterozygous or homozygous familial hypercholesterolemia, patients intolerant of statins, and patients with varied cardiovascular risk not at LDL-C goal with statin therapy 3, 4.
• Both alirocumab and evolocumab have been shown to be effective in reducing the risk of major cardiovascular events (MACE) in patients with HLD 6, 7.
• The safety profiles of alirocumab and evolocumab are similar, with no significant differences in adverse events or discontinuation rates between the two medications 6, 7.

Comparison of Alirocumab and Evolocumab

• A register-based cohort study found that both alirocumab and evolocumab were effective in reducing LDL-C levels, with no significant difference in LDL-C levels or adverse clinical outcomes between the two medications 6.
• A systematic review and meta-analysis found that both alirocumab and evolocumab reduced the risk of CVD events, mortality, and MI, with high-certainty evidence for these outcomes 7.
• However, the evidence base for PCSK9 inhibitors compared with active treatment is weaker, and it is unclear whether evolocumab or alirocumab might be effectively used as replacement therapies 7.