alirocumab

Alirocumab (brand name Praluent) is a fully human monoclonal IgG antibody that targets PCSK9, an enzyme that normally binds to LDL receptors on hepatocytes and promotes their lysosomal degradation. By inhibiting PCSK9, alirocumab prevents LDL receptor degradation, increasing the number of LDL receptors available on the hepatocyte surface. This enhances clearance of LDL cholesterol from the bloodstream, resulting in LDL-C reductions of 50-60% when added to statin therapy. It is administered as a subcutaneous injection every 2 or 4 weeks.

Clinical indications include: (1) heterozygous familial hypercholesterolemia, (2) established ASCVD requiring additional LDL lowering beyond maximally tolerated statin therapy, and (3) as monotherapy in statin-intolerant patients. Landmark trials like ODYSSEY OUTCOMES demonstrated reduction in major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome.

Mechanistically, this drug class (PCSK9 inhibitors, which also includes evolocumab) represents a novel non-statin approach to lipid management, particularly valuable in patients with statin-associated muscle symptoms or those needing additional LDL lowering despite maximal statin/ezetimibe therapy.

Adverse effects are generally mild and include injection site reactions, nasopharyngitis, and rarely neurocognitive effects (though this remains debated in trial data). Unlike statins, PCSK9 inhibitors do not cause significant hepatotoxicity or myopathy, making them useful alternatives in statin-intolerant patients.

Boards-relevant pearls: Know the mechanism (PCSK9 inhibition → increased LDL receptor recycling → decreased serum LDL), the route of administration (SC injection, not oral), and its use in high-risk patients not at goal despite statin therapy. Contrast with statins (HMG-CoA reductase inhibitors) and ezetimibe (cholesterol absorption inhibitor) as other lipid-lowering mechanisms.