Olpasiran Reduces Cardiovascular Risk by Lowering Lp(a)

A recent clinical trial has shed light on the efficacy of an RNA inhibitor, olpasiran, in reducing lipoprotein(a) [Lp(a)], a type of "bad cholesterol" that significantly contributes to the risk of cardiovascular diseases. The findings, published on February 12, 2025 in JAMA Cardiology, mark a breakthrough in the treatment of patients suffering from atherosclerosis.

The Significance of Lipoprotein(a)

Atherosclerosis is a condition characterized by the buildup of fats, cholesterol, and other substances in and on the artery walls, leading to the narrowing and hardening of the arteries. This condition can result in severe health issues, including angina pectoris and heart attacks.
Lipoprotein(a) has emerged as a significant risk factor associated with these cardiovascular events. It is known to carry a cardiovascular risk that is estimated to be five to six times greater than that of low-density lipoprotein (LDL) cholesterol.

Trial Overview

The clinical trial, known as OCEAN(a)-DOSE, involved 282 patients with pre-existing cardiovascular disease and elevated Lp(a) levels (>150 nmol/L or 60 mg/dL). These elevated levels are implicated in promoting clotting and inflammation, thus raising the risk of cardiovascular events.

Key Findings

The analysis found that participants receiving doses of 75 mg or higher of olpasiran every 12 weeks experienced a remarkable reduction in Lp(a) levels of greater than 95% at 36 weeks compared to the placebo group, which showed an average increase of 3.6% in Lp(a) levels over the same period. The following table summarizes the outcomes of the trial:

Dr. Robert Rosenson, Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai and lead researcher of the trial, stated: "Our study is the first clinical trial to investigate the association between oxidized phospholipids on lipoprotein(a) and cardiovascular disease."

Impact on Inflammation

Besides Lp(a) reduction, olpasiran also significantly decreased levels of oxidized phospholipids, substances believed to exacerbate atherosclerosis. The study reported:

• Oxidized Phospholipids: The olpasiran-treated group showed lower levels, indicating a potentially reduced risk for future cardiovascular events.
• Proinflammatory Cytokines: There was no significant difference noted in the secretion of interleukin-6 or C-reactive protein when compared to the placebo group, suggesting that the reduction in Lp(a) may not directly correlate with pro-inflammatory processes.

Conclusion and Future Directions

This promising data suggests that olpasiran could represent a novel approach in combating cardiovascular diseases linked to elevated Lp(a). However, Dr. Rosenson emphasizes that further studies are essential to understand the anti-inflammatory responses associated with RNA inhibitors effectively. As the Phase III outcomes trial for olpasiran is underway, researchers are hopeful that these innovative therapies will pave the way for better management of cardiovascular diseases.

Further Reading

For additional information on olpasiran and its effects, see the article titled “Olpasiran, Oxidized Phospholipids, and Systemic Inflammatory Biomarkers” published in JAMA Cardiology.

References

• Rosenson, R. et al. (2025). _JAMA Cardiology_, Olpasiran, Oxidized Phospholipids, and Systemic Inflammatory Biomarkers.
• Mount Sinai - Fuster Heart Hospital.
• Wikipedia contributors. (2023). Atherosclerosis. Wikipedia, The Free Encyclopedia.