Physicians' Academy for Cardiovascular Education

Total CV events lowered by PCSK9i-induced Lp(a) reduction in ACS patients

Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering: ODYSSEY OUTCOMES trial

Literature - Szarek M, Bittner VA, Aylward, P, et al. - Eur Heart J. 2020;ehaa649. doi: 10.1093/eurheartj/ehaa649.

Introduction and methods

Elevated baseline levels of lipoprotein(a) [Lp(a)] have been associated with first CV outcome in epidemiological studies and Mendelian randomization analyses [1-3]. Recently, it has been shown in patients treated with a PCSK9 inhibitor, that reduction in Lp(a) can predict reduction in risk of a first CV event, independent of LDL-c levels [4]. Similar results have been reported for first PAD or VTE events [5]. However, the risk reduction on total CV burden has not been analyzed yet.

This post-hoc analysis of the ODYSSEY OUTCOMES trial in patients with acute coronary syndrome (ACS) receiving intensive statin therapy, evaluated whether baseline Lp(a) levels and reduction in Lp(a) and LDL-c corrected for Lp(a) cholesterol (LDL-c[corr]) by alirocumab treatment could independently predict total CV events.

Patients (n=18924, ≥40 years) who were 1-12 months before randomization hospitalized with ACS (MI or unstable angina) were included in the trial. Participants had to have an LDL-c of ≥70 mg/dL (1.81 mmol/L), or a non-HDL-c of ≥100 mg/dL (2.59 mmol/L), or apolipoprotein B of ≥80 mg/dL, measured during stable treatment with atorvastatin 40-80 mg daily, or rosuvastatin 20-40 mg daily, or the maximum tolerated dose of either statin. Patients were randomized in a 1:1 ratio to 75 mg of alirocumab or matching placebo given every 2 weeks by subcutaneous injection. The median follow-up was 2.8 years (2.3-3.4 years).

For the present analysis, all CV outcomes collected in the trial including, CV death, hemorrhagic stroke, hospitalization for HF, ischemia-driven coronary revascularization, major PAD event (critical limb ischemia, lower extremity revascularization, and amputation due to ischemia), and VTE (deep vein thrombosis and pulmonary embolism) were examined.

Main results


This study showed that LDL-c[corr] and Lp(a) reductions by alirocumab in patients with ACS, were independently associated with fewer total CV events. Although most risk reduction was attributed to a lowered LDL-c[corr], the contribution of reduced Lp(a) levels to reduce the risk of CV events was most evident in individuals with high Lp(a) baseline levels.


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Find this article online at Eur Heart J.

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