Emerging RNA therapeutics to lower blood levels of Lp(a)

Four years after his Lp(a) primer, Tsimikas and colleagues focus specifically on the therapies — the RNA-based drugs poised to make elevated Lp(a) treatable for the first time.

The review explains the approach: antisense oligonucleotides like pelacarsen, and related RNA agents, silence the gene that builds apolipoprotein(a), cutting Lp(a) levels by up to 80%. Early trials showed safety and large reductions in the marker, which is what launched the big Phase 3 outcome trial designed to prove whether lowering Lp(a) translates into fewer cardiovascular events.

The practical takeaway is anticipatory: RNA therapeutics are a genuinely new tool, and clinicians should expect potential practice change once outcomes data arrive. The resistance is the historical neglect of Lp(a), born of having nothing to offer.

We rate the evidence moderate: an expert JACC review with fully disclosed conflicts (Tsimikas’s Ionis ties). Its clinical significance is high in prospect — these drugs could finally answer the decades-old Lp(a) question — and it sits alongside the other Lp(a)-therapy reviews in this library, all converging on trials now underway.