Lipoprotein(a) Reduction in Persons with Cardiovascular Disease

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Genetics

Background:

• Elevated lipoprotein(a) [Lp(a)] levels are genetically determined and a significant risk factor for cardiovascular disease (CVD) and aortic stenosis.
• Currently, no approved pharmacologic therapies exist to effectively lower Lp(a) levels.

Purpose of the Study:

• To evaluate the efficacy and safety of the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-L_Rx (APO(a)-L_Rx) in reducing lipoprotein(a) levels.
• To determine the dose-dependent effect of APO(a)-L_Rx in patients with established cardiovascular disease and elevated Lp(a).

Main Methods:

• A randomized, double-blind, placebo-controlled, dose-ranging trial was conducted with 286 patients.
• Patients received varying doses of APO(a)-L_Rx or placebo subcutaneously for 6 to 12 months.
• The primary endpoint was the percent change in lipoprotein(a) level from baseline to 6 months, measured by an isoform-independent assay.

Main Results:

• APO(a)-L_Rx demonstrated dose-dependent reductions in lipoprotein(a) levels, with mean decreases ranging from 35% to 80% across different doses.
• The highest dose (20 mg weekly) achieved an 80% reduction, compared to only 6% with placebo (P < 0.001).
• No significant differences were observed in platelet counts, liver/renal function, or influenza-like symptoms between treatment groups; injection-site reactions were the most common adverse events.

Conclusions:

• APO(a)-L_Rx effectively and significantly reduced lipoprotein(a) levels in a dose-dependent manner.
• The findings support APO(a)-L_Rx as a potential therapeutic agent for patients with elevated Lp(a) and established cardiovascular disease.
• Further research is warranted to explore its long-term impact on cardiovascular outcomes.