Two major cardiovascular programs—one targeting lipoprotein(a) and another aimed at IL-6-mediated inflammation—failed to improve hard outcomes despite lowering biomarkers, according to results presented at the American Heart Association meeting and published alongside. A Phase 3 pelacarsen study (HORIZON) lowered Lp(a) but did not reduce heart attacks, strokes, urgent coronary revascularization, or deaths. Separately, Novo Nordisk’s ziltivekimab (ZEUS) reduced IL-6 but also did not translate into fewer serious cardiovascular events, with Novo halting other ziltivekimab trials after poor outlook from monitoring. The pattern adds to a growing evidence base questioning whether biomarker modulation alone is sufficient for event reduction in cardiovascular risk reduction programs.