Alirocumab benefits CAD patients only if lipoprotein (a) levels elevated: Study

Various Guidelines recommend non-statin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk.

A post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial was performed by a group of authors from U.S.A. to evaluate the benefit of adding the proprotein subtilisin/Kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels.

The researchers conducted the ODYSSEY Outcomes, wherein they compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL; in 14,573 patients (77.0%), both determinations were ≥70 mg/dL.

The results of the study are as follows:

• In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL).
• Corresponding adjusted treatment hazard ratios were 0.68, with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017).
• In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 and 0.89, with Pinteraction = 0.43.

The researchers concluded that in patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated.

Reference:

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol by Schwartz G et. al published in the J Am Coll Cardiol.

https://www.jacc.org/doi/abs/10.1016/j.jacc.2021.04.102