Two recent clinical trials have raised new questions about whether lowering specific cardiovascular biomarkers is enough to prevent heart attacks and strokes.
The first involved ziltivekimab, an experimental drug from Novo Nordisk designed to target inflammation associated with high-sensitivity C-reactive protein (hsCRP). In the Phase 3 ZEUS trial, the drug successfully affected the intended inflammatory pathway and reduced hsCRP, but it did not significantly reduce major adverse cardiovascular events compared with placebo. The trial included more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and elevated inflammation.
The second trial tested pelacarsen, an investigational drug designed to lower lipoprotein(a), or Lp(a). In the Phase 3 Lp(a)HORIZON study, pelacarsen substantially reduced Lp(a) levels but failed to meet its primary endpoint for reducing cardiovascular events. The study involved more than 8,000 participants with elevated Lp(a) and established cardiovascular disease.
The results do not mean that hsCRP or Lp(a) are irrelevant. Instead, they highlight the difference between a biomarker being associated with cardiovascular risk and proving that changing that biomarker will reduce clinical events.
The findings also reinforce the importance of established approaches to cardiovascular risk reduction, including managing blood pressure and cholesterol, avoiding tobacco, maintaining physical activity and following a healthy diet.
For researchers, the failed trials provide new evidence about how cardiovascular risk pathways work and how future treatments targeting inflammation or Lp(a) should be evaluated.