Highly anticipated cholesterol drug fails to prevent heart attacks, strokes
An experimental drug from Novartis, pelacarsen, designed to lower the genetic form of cholesterol known as lipoprotein(a) or Lp(a), failed to reduce heart attacks, strokes, or related cardiovascular outcomes in the Horizon trial, despite a substantial 78% drop in Lp(a) levels in participants. The study involved 8,322 individuals with high Lp(a) who had prior heart events, and results published with surprise among researchers. Possible explanations include late intervention timing, concurrent aggressive LDL and blood pressure management, and the fixed, genetic nature of Lp(a). No further pelacarsen studies are planned, while other Lp(a)-lowering approaches are underway, keeping cautious optimism for future breakthroughs.
Dive Deeper:
Lp(a) is a genetic cholesterol form that promotes arterial plaque buildup and clot formation; unlike diet-driven cholesterol, it cannot be altered by lifestyle changes alone.
The Horizon trial enrolled 8,322 participants with high Lp(a) who had a recent or prior heart event within ten years, spanning nearly 800 sites.
Pelacarsen reduced Lp(a) levels by about 78% versus a 13% reduction with placebo, yet this biochemical success did not translate into fewer strokes, heart attacks, cardiovascular deaths, or revascularization procedures.
Researchers noted the average participant was around 60 years old and followed for roughly five years, suggesting timing might influence effectiveness.
Experts highlighted that broad risk reduction strategies (LDL control, blood pressure management, and possible aspirin use) could confound Lp(a)’s isolated impact on outcomes.
The trial results were published in the New England Journal of Medicine, with leadership from Dr. Steven Nissen, who described the findings as unexpectedly neutral.
Future Lp(a)–targeting approaches are in development, including Eli Lilly’s lepodisiran, Amgen’s olpasiran, and Silence Therapeutics’ zerlasiran, using different technologies and potentially different safety profiles.