Lipoprotein(a), PCSK9 Inhibition and Cardiovascular Risk: Insights from the FOURIER Trial

Background: Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition and cardiovascular (CV) risk reduction remains undefined. Methods: Lp(a) was measured in 25,096 patients in FOURIER, a randomized trial of evolocumab versus placebo in patients with established atherosclerotic CV disease (median follow-up 2.2 years). Cox models were used to assess the independent prognostic value of Lp(a) and the efficacy of evolocumab for coronary risk reduction by baseline Lp(a) concentration. Results: The median [IQR] baseline Lp(a) concentration was 37[13-165] nmol/L. In the placebo arm, patients with baseline Lp(a) in the highest quartile had a higher risk of coronary heart disease (CHD) death, MI or urgent revascularization (UR) (adjusted HR Q4:Q1 1.22, 95% CI 1.01-1.48) independent of LDL-C. At 48 weeks, evolocumab ...