Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing...

Area of Science:

• Cardiovascular Medicine
• Clinical Lipidology
• Pharmacology

Background:

• A continuous relationship between LDL-C reduction and MACE has been observed down to 54 mg/dL.
• Uncertainty exists regarding the MACE-LDL-C relationship at levels below 50 mg/dL.
• The ODYSSEY trials investigated alirocumab's efficacy in reducing LDL-C and MACE.

Purpose of the Study:

• To assess the relationship between additional LDL-C, non-HDL-C, and ApoB-100 reductions and MACE.
• To determine if LDL-C reduction benefits extend to levels below 50 mg/dL.

Main Methods:

• Pooled data from 10 double-blind ODYSSEY trials (4974 patients, 6699 patient-years).
• Alirocumab or control treatment added to maximally tolerated statin therapy.
• Post hoc analysis correlating on-treatment lipid levels and percent reductions with MACE incidence.

Main Results:

• 33.1% of patients achieved average LDL-C <50 mg/dL.
• A 24% lower risk of MACE for every 39 mg/dL decrease in LDL-C (aHR=0.76).
• Inverse correlation between LDL-C percent reduction and MACE rates (HR=0.71 per 50% reduction). Similar associations for non-HDL-C and ApoB-100.

Conclusions:

• Greater LDL-C reduction and lower on-treatment levels, including <50 mg/dL, are associated with reduced MACE incidence.
• Findings suggest continued benefit from aggressive LDL-C lowering.
• Further validation is required in the ongoing ODYSSEY OUTCOMES trial.