TOPLINE:

Patients with atherosclerotic cardiovascular disease (ASCVD) who had lower levels of lipoprotein(a), referred to as Lp(a), did not have an increased risk for safety concerns such as bleeding, stroke, or cancer but had a modestly higher risk of developing diabetes.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the FOURIER trial, in which patients with ASCVD were randomly assigned to receive evolocumab or placebo in addition to statin therapy, to assess whether lower baseline or achieved Lp(a) levels were linked to safety concerns.
• A total of 25,090 patients had Lp(a) levels assessed at baseline, and 26,619 patients had Lp(a) levels assessed at week 12. The median age of the patients was 63 years, and 68%-80% were men.
• Patients were classified into quartiles based on baseline Lp(a) levels. The median baseline level of Lp(a) was 37 nmol/L.
• Researchers assessed safety outcomes, including prevalent and new‑onset diabetes, hemorrhagic stroke, serious bleeding, neurocognitive events, new or progressive cancer, and incident and prevalent atrial fibrillation.
• Patients were followed up for a median of 2.2 years.

TAKEAWAY:

• Lower baseline Lp(a) levels were not linked to a higher risk for hemorrhagic stroke, serious bleeding, neurocognitive events, new or progressive cancer, or atrial fibrillation.
• Each 50 nmol/L decrease in the baseline Lp(a) level was linked to 3% higher odds of prevalent diabetes (P < .001) and a 5% increased risk for new-onset diabetes (P = .002).
• The inverse relationship between Lp(a) levels and the risk for diabetes was consistent in both the evolocumab and placebo groups and when using week-12 Lp(a) values.
• Evolocumab treatment was not associated with an increased risk for diabetes, even among patients in the top decile of baseline Lp(a) levels who experienced a median reduction of 71 nmol/L in Lp(a) levels with therapy.

IN PRACTICE:

“Since Lp(a) is primarily genetically determined, these observations provide supportive evidence regarding the safety of living with low Lp(a) values,” the researchers wrote.

SOURCE:

The study was led by Baris Gencer, MD, of Geneva University Hospitals in Geneva, Switzerland. It was published online on June 3 in the European Heart Journal.

LIMITATIONS: 

The analysis was post hoc and exploratory and could not prove that low Lp(a) levels caused the observed associations. The follow-up duration was relatively short. Some safety events were rare, and so the study was underpowered to detect associations for uncommon outcomes.

DISCLOSURES:

The FOURIER trial received research grant support from Amgen. Several authors reported receiving honoraria, speaker fees, consulting or advisory board payments, and having other financial relationships with multiple sources, including Amgen.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.