AKCEA-APO(a)-LRx – a second generation, N-acetyl-galactosamine-conjugated, antisense oligonucleotide targeted to apolipoprotein(a) – may reduce Lp(a) levels in patients with preexisting cardiovascular disease, according to results of the AKCEA trial presented Nov. 10 at AHA 2018 in Chicago, IL.

Sotirios Tsimikas, MD, FACC, et al., looked at 286 patients with preexisting cardiovascular disease (coronary artery disease, myocardial infarction, peripheral artery disease, stroke/transient ischemic attack) and baseline Lp(a) ≥60 mg/dL who were randomized to receive 20, 40 or 60 mg of AKCEA-APO(a)-LRx per month, 20 mg/every two weeks, or 20 mg per week, for a minimum of 6 months vs. placebo.

Results showed that AKCEA-APO(a)-LRx significantly and "dose-dependently" reduced Lp(a) levels, with "98 percent of patients achieving Lp(a) levels ≤50 mg/dL at the highest dose." The researchers add that it also reduced OxPL-apoB, OxPL-apo(a), LDL-C and apoB levels. Further, a favorable safety profile was noted with no significant liver, renal or platelet adverse events vs. placebo.

The authors conclude that moving forward, this study "provides a rationale for the initiation of a phase 3 outcomes trial to test the 'Lp(a) hypothesis,' namely that lowering Lp(a) levels will reduce cardiovascular events."

Keywords: AHA18, AHA Annual Scientific Sessions, Lipoprotein(a), Apolipoproteins A, Cardiovascular Diseases

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