PCSK9 inhibitors

In people at high risk, the evidence is strong. Evolocumab cut LDL to a median 30 mg/dL (0.78 mmol/L)0.78 mmol/L (30 mg/dL) and lowered cardiovascular events by 15% in patients with heart disease [1], and alirocumab lowered events after a heart attack [2]. In 2025 the VESALIUS-CV trial extended this to 12,257 people with atherosclerosis or diabetes but no prior heart attack or stroke: first major events fell by a quarter over about 5 years [3].

Genetics supports the idea that lower LDL for life protects the heart. People born with PCSK9 variants that lower LDL had far less coronary heart disease over 15 years [4].

What is not known is the benefit for lean, fit people at low risk, who were not in the trials. Very low LDL did not harm thinking over about 5 years in one follow-up study [5], but data on decades of use in healthy people do not exist.

• Evolocumab and alirocumab are approved for adults with cardiovascular disease, high risk or familial hypercholesterolemia. Use in low-risk healthy people is off-label in spirit and untested in trials.
• Side effects in trials were close to placebo apart from injection site reactions; cold-like symptoms and flu-like symptoms are reported.
• They are injected every 2 to 4 weeks and are expensive; insurers usually require high risk or high LDL first.
• Safety data run about 5 to 8 years. Lifelong use from a young age has not been studied, and use in pregnancy has little data.