Small, dense LDL-C as a predictor of cardiovascular risk and benefit of alirocumab in patients with recent acute coronary syndrome receiving optimized statin treatment.

INTRODUCTION

Small, dense low-density lipoprotein (sdLDL) particles are considered a highly atherogenic subfraction of LDL. Automated biochemical measurement of sdLDL cholesterol (sdLDL-C) has good fidelity to gold-standard measurements. We evaluated relationships of sdLDL-C and LDL-C to risk of major adverse cardiovascular events (MACE) and treatment benefit of the PCSK9-directed monoclonal antibody alirocumab in patients with recent acute coronary syndrome (ACS) and elevated atherogenic lipoproteins despite optimized statin treatment.

METHODS

Analyses comprised 11,837 participants in the ODYSSEY OUTCOMES trial randomized to receive alirocumab or placebo. sdLDL-C was measured using the Denka method; baseline LDL-C was calculated with the Friedewald formula. In the placebo group (n = 5920), cubic splines depicted relationships of sdLDL-C, LDL-C, and their ratio to risk of MACE (cardiovascular death, non-fatal myocardial infarction, ischemic stroke, hospitalization for unstable angina, and ischemia-driven coronary revascularization). Treatment hazard ratio (HR) was calculated across sdLDL-C and LDL-C ranges.

RESULTS

Over 2.8 years median follow-up, risk of MACE in the placebo group increased with higher baseline sdLDL-C or LDL-C with nearly superimposable splines and without variation according to sdLDL-C/LDL-C. Findings were similar in patients with greater or lesser degrees of insulin resistance. Alirocumab reduced risk of MACE (HR 0.87, 95% CI 0.79, 0.95). Treatment HR did not vary significantly across the range of LDL-C or sdLDL-C.

CONCLUSION

In patients with recent ACS on optimized statin treatment, sdLDL-C and LDL-C similarly predict risk of MACE and benefit of alirocumab treatment. Measurement of sdLDL-C does not appear to provide additional prognostic or predictive information in this population.