In follow up to my recent blog post, we now have the detailed results from the FOURIER trial, demonstrating that the PCSK9 inhibitor evolocumab reduces cardiovascular events in patients with cardiovascular disease.
Just published (and free to read online) in the New England Journal of Medicine, this large study randomized 27,564 patients to either evolocumab or placebo, to examine the impact on the primary endpoint of cardiovascular death, heart attack, stroke, hospitalization for unstable angina, or coronary revascularization. Patients in the study already had existing cardiovascular disease, had a bad cholesterol (LDL) of 1.8 mmol/L or greater, and were all on statin therapy (the current gold standard group of lipid lowering medications).
After a median of 2.2 years, evolocumab reduced cardiovascular events by 15%, with 9.8% of patients on treatment having an event, vs 11.3% of patients on placebo. This difference was driven by a reduction in heart attack, stroke, and coronary revascularization, with no significant difference in cardiovascular death or hospitalization for unstable angina.
Evolocumab reduced LDL by 59%, from a median baseline value of 2.4 mmol/L to 0.78 mmol/L. The reduction in cardiovascular events was consistent, regardless of baseline LDL. The only side effect that was significantly different between the evolocumab vs placebo groups was injection site reaction, seen in 2.1% vs 1.6% of patients respectively.
While these results give us important information regarding the benefit of evolocumab in patients with established cardiovascular disease, we still need data to know if these benefits would also be enjoyed by people with high cardiovascular risk but without established cardiovascular disease. We also need to know more about long term effects of PCSK9 inhibitors. As noted in the accompanying editorial, it is not known whether prolonged exposure to extremely low LDL levels could affect neurocognitive function (though no difference was seen in the FOURIER study); longer term studies are underway.
The benefits of additional LDL lowering with evolocumab in addition to statins to reduce cardiovascular events in patients with established cardiovascular disease are clear from this study. Cost of currently available PCSK9 inhibitors (evolocumab and alirocumab) are currently a major limitation to their use, but hopefully this will change with time as evidence regarding benefits hopefully accumulate.
Disclaimer: I have been involved as an investigator in a clinical trial of PCSK9 inhibition.