Alirocumab-induced Lp(a) lowering independently predicts fewer MACE after ACS: ODYSSEY OUTCOMES (Bittner et al., JACC 2020)

Original title: Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

J Am Coll Cardiol · 21 January 2020 · 8

Bittner VA, Szarek M, Aylward PE, Bhatt DL, Diaz R, Edelberg JM, Fras Z, Goodman SG, Halvorsen S, Hanotin C, Harrington RA, Jukema JW et al.

In 18,924 patients on high-intensity statins after acute coronary syndrome, baseline Lp(a) (median 21 mg/dL) and corrected LDL-C both predicted MACE; alirocumab lowered Lp(a) by a median 5 mg/dL and corrected LDL-C by 51 mg/dL, and each reduction independently predicted lower MACE risk, the Lp(a) effect being larger in patients with higher baseline Lp(a). Together with FOURIER, the evidence that part of the PCSK9-inhibitor benefit runs through Lp(a).

Original abstract

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C).

Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE).

Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina.

Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081).

Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.