Evolocumab reduces Lp(a) levels in atherosclerotic CVD

Michelle L. O’Donoghue

Lipoprotein(a) was significantly reduced in patients treated with evolocumab, and those with the highest levels at baseline had the greatest benefit from this PCSK9 inhibitor, according to data presented at the 86th Annual Congress of the European Atherosclerosis Society.

“Lp(a) may be a useful marker for helping to identify patients who derive greater absolute benefit from a PCSK9 inhibitor,” Michelle L. O’Donoghue, MD, cardiovascular medicine specialist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, told Cardiology Today. “Since individuals with a higher Lp(a) concentration were at higher risk of events, the number needed to treat with evolocumab to prevent a major cardiovascular event was reduced in half.”

Researchers assessed the effect of evolocumab (Repatha, Amgen) on Lp(a) levels and CV risk in 27,574 patients (median Lp(a), 37 nmol/L) with atherosclerotic CVD from the FOURIER trial.

As Cardiology Today previously reported, the FOURIER trial found that a reduction of LDL to a median of 30 mg/dL with the PCSK9 inhibitor evolocumab in patients with atherosclerotic CVD was associated with lowered risk for CV events.

Patients were assigned evolocumab or placebo for a median of 2.2 years.

Compared with the lowest quartile, patients in the placebo group who had Lp(a) levels in the highest quartile at baseline had the highest risk for MI or CHD death (adjusted HR = 1.26; 95% CI, 1.02-1.56).

Patients assigned evolocumab had a 26.9% reduction in Lp(a) levels at 48 weeks. The correlation coefficient between percent change in Lp(a) and LDL in the evolocumab group at 48 weeks was 0.37 (P < .001).

The risk for MI, CV death or stroke was reduced by 24% in patients assigned evolocumab who had a baseline Lp(a) level greater than the median. The absolute risk reduction for patients with higher baseline risk was 2.8% and the number needed to treat was 36.

This risk also decreased by 15% in patients with baseline Lp(a) levels less than the median, with an absolute risk reduction of 1.3% and a number needed to treat of 79 for patients with higher baseline risk.

Patients who achieved Lp(a) and LDL levels below the median had the lowest risk for CV events at 12 weeks.

“The ultimate question that remains is whether therapies that directly inhibit Lp(a) will further reduce the risk of cardiovascular events,” O’Donoghue said in an interview. “Novel therapies are being developed in that regard.” – by Darlene Dobkowski

Reference:

O’Donoghue ML, et al. Late Breaking – Clinical Trials. Presented at: 86th Annual Congress of the European Atherosclerosis Society; May 5-8, 2018; Lisbon, Portugal.

Disclosures: The FOURIER trial was supported by a grant from Amgen. O’Donoghue reports she received grant support from Amgen for an unrelated project.