Recent top-line results from two major trials have disappointed preventive cardiologists. The Lp(a) HORIZON trial tested pelacarsen, designed to lower lipoprotein(a), a genetically inherited cholesterol particle tied to heart attack and stroke risk. While the drug did lower Lp(a) levels, it failed to reduce cardiovascular events.
Weeks earlier, the ZEUS trial of Novo Nordisk's ziltivekimab, a monoclonal antibody targeting IL-6, also hit its biological target without improving clinical outcomes. Both studies underscore a recurring problem: surrogate biomarkers do not always translate into real-world patient benefit.
The author, a preventive cardiologist at Northwestern University, argues these results force a hard look at precision medicine's promise in cardiology. The trials do not necessarily invalidate the therapeutic targets, but they highlight the need to wait for outcome data before assuming that changing a biomarker matters.