BACKGROUND Guidelines recommend nonstatin 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. OBJECTIVES In a post hoc analysis of the ODYSSEY
Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During
Treatment With Alirocumab) trial, the authors evaluated 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. METHODS ODYSSEY Outcomes 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 (median
69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both
determinations were >= 70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0
mg/dL). RESULTS 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 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49),
with treatment-lipoprotein(a) interaction on MACE (P-interaction = 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 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06),
with P-interaction = 0.43. CONCLUSIONS 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. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes
After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C)
2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology
Foundation.
