Longevity & AgingPelacarsen slashes Lp(a) by 78% yet fails to cut heart attacks and strokes
Lipoprotein(a), or Lp(a), is an inherited cholesterol-carrying particle that raises the risk of heart disease and aortic stenosis, and diet or exercise barely changes it. The Lp(a) HORIZON trial tested pelacarsen, an antisense drug that cuts Lp(a) production in the liver, in people with high Lp(a) and existing cardiovascular disease. Pelacarsen lowered Lp(a) by about 78% and LDL cholesterol by about 13%, yet over nearly five years it did not reduce the combined risk of cardiovascular death, stroke, heart attack, or urgent revascularization (HR 1.02). Results were also neutral in those with very high Lp(a). Discontinuation due to side effects was far higher on the drug (20.6% vs 7.5%). Researchers say this may end pelacarsen's road, but not the Lp(a) hypothesis. Trials in primary prevention, aortic stenosis, and with siRNA drugs continue.
