Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial

Abstract

Amgen.

Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials

“…Later analysis from the overall FOURIER cohort has shown a strong relationship between lower achieved LDL‐C, including to very‐low LDL‐C levels, and a progressive reduction of cardiovascular events,25 consistent with our observation of a lower rate of MACE in women and men with lower on‐treatment LDL‐C levels (Figure 4A). In line with results from the FOURIER trial8 and the CTT Collaboration,4 in our study, the P for heterogeneity between men and women was not significant for overall effects.…”

PCSK9 Inhibitors in Lipid Management of Patients With Diabetes Mellitus and High Cardiovascular Risk: A Review

“…The magnitude of cardiovascular benefit of evolocumab in FOURIER (with a reduction in LDL‐C from 92 to 30 mg/dL) over 2.2 years63 was close to the range expected based on the Cholesterol Treatment Trialists’ meta‐analysis of statin trials, which reported a 22% relative risk reduction over 5 years per 1 mmol/L (39 mg/dL) LDL‐C reduction 87. Improved cardiovascular outcomes were observed down to LDL‐C levels as low as 8 mg/dL, with no significant associations between such very low LDL‐C levels and AEs 88. Together with the GLAGOV findings, these results show that patients with ASCVD benefit from LDL‐C lowering below current targets 63.…”

Proprotein Convertase Subtilisin-Kexin Type 9 (PCSK9) Inhibitors and Cardiovascular Risk: Does a Further Analysis of the Fourier Trial Suggest Changes in the Target of Lipid Lowering Therapy?

“…statin with or without ezetimibe) (-27% myocardial infarction, -21% stroke, -22% coronary revascularizations) during a median period of 2.2 years of follow up. Thus, in the FOURIER trial achieved LDL-C concentration were substantially lower than those observed in all of the previous clinical trials with any lipid-lowering therapy [8] including the IMPROVE-It trial [5].…”

“…In some preliminary analyses, the benefits obtained by the reduction in serum LDL-C levels to 30 mg/dl were claimed to be not linearly correlated to the achieved serum LDL-C concentrations [8]. Thus, the reduction in cardiovascular events seemed lower than expected and thereby suggested the existence of a plateau of the benefits obtainable by lipid lowering strategies.…”