Available online 10 April 2024

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Alirocumab improves cardiovascular outcomes after ACS irrespective of sex.

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Reduction of total cardiovascular events was greater at higher baseline Lp(a).

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A lipoprotein(a)-dependent treatment benefit may be more evident in women.

AbstractBackground

The ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS).

Objective

We assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level.

Methods

This prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment.

Results

Women were older, had higher baseline LDL-C levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p<0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes.

Conclusions

Alirocumab improves cardiovascular outcomes after ACS irrespective of sex.

Summary

After recent ACS, addition of alirocumab to GDMT improves outcomes consistently in women and men. Reduction of total cardiovascular events was greater at higher baseline Lp(a).

KEYWORDS

Acute Coronary Syndrome

Sex

Alirocumab

PCSK9 inhibition

Cholesterol

Cardiovascular Outcomes

Lipoprotein(a)

AbbreviationsACS

acute coronary syndrome

ARR

absolute rate reduction

CHD

coronary heart disease

HDL-C

high-density lipoprotein cholesterol

LDL-C

low-density lipoprotein cholesterol

MACE

major adverse cardiovascular events

NSTEMI

non-ST-segment elevation myocardial infarction

Non-HDL-C

non-high-density lipoprotein cholesterol

PCSK9

proprotein convertase subtilisin/kexin type 9

STEMI

ST-segment elevation myocardial infarction

© 2024 Published by Elsevier Inc. on behalf of National Lipid Association.