Proprotein convertase subtilisin/kexin type 9 inhibitors for reduction of cardiovascular events

The efficacy, safety, and place in therapy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for lipid lowering are reviewed.

PCSK9 inhibitors are injectable monoclonal antibodies that increase the availability of low-density lipoprotein (LDL) receptors, resulting in a reduction in serum LDL cholesterol (LDL-C). The currently available PCSK9 inhibitors alirocumab and evolocumab were shown to reduce LDL-C concentrations by approximately 55-60% relative to placebo use when used as monotherapy or added to other lipid-lowering therapies. A large randomized controlled trial of evolocumab demonstrated a reduction in cardiovascular events that translated to a 16% relative risk reduction per 1-mmol/L (39-mg/dL) reduction in LDL-C over 2 years, nearly identical to risk reductions reported with use of statins for LDL-C lowering. Another large outcome trial with alirocumab is ongoing. PCSK9 inhibitors are well tolerated, and minor injection-site reaction is the only known adverse effect. Routine use of these agents in all patients with cardiovascular disease is not cost-effective at the current annual cost of therapy of approximately $14,000 in the United States and $7,000 in other Western countries. Careful patient selection may increase the benefit-to-cost ratio of these agents.

The PCSK9 inhibitors alirocumab and evolocumab, as adjuncts to oral lipid-lowering agents or as monotherapy, lower serum LDL-C concentrations and reduce the risk of cardiovascular events. These agents are safe and well tolerated, but high cost and lack of cost-effectiveness limit their routine use.