Proprotein convertase subtilisin kexin 9 (
PCSK9) inhibitors have emerged as a novel treatment option in patients with
hypercholesterolemia.
Evolocumab and
alirocumab have achieved consistent and significant (around 60%) reduction in
low-density lipoprotein cholesterol (
LDL-C) levels when added to
statin therapy in short term studies. The Open-Label Study of Long-term Evaluation Against
LDL-C (OSLER), and The Long-term Safety and Tolerability of
Alirocumab in High Cardiovascular Risk Patients with
Hypercholesterolemia Not Adequately Controlled with Their
Lipid Modifying
Therapy (ODYSSEY LONG TERM) studies are two phase 3, multicentre, randomized, placebo controlled studies that were conducted to evaluate the long term efficacy and safety of
evolocumab and
alirocumab respectively in reducing
lipids and cardiovascular (CV) events. Both studies demonstrated additional 48-53% reduction of CV events when added to
statin therapy. Most adverse events occurred with similar frequency in the two groups; however the rate of neurocognitive adverse events was higher with
evolocumab and
alirocumab than with placebo. These data provide strong support for the notion that lower
LDL-C goal is better, and may confirm the role of
PCSK9 inhibitors as a new frontier in
lipid management. The results of larger long-term outcome studies are still awaited.