Heart drugs miss the mark despite hitting key targets

Two drugs intended to treat heart disease did not improve patient outcomes in large-scale clinical trials, even though they effectively targeted biological markers tied to cardiovascular risk. Novartis’s pelacarsen and Novo Nordisk’s ziltivekimab underwent late-stage testing but showed no advantage over placebos in preventing heart attacks, strokes, or death.

Pelacarsen successfully drove down lipoprotein(a) levels by 78 percent in the trial of 8,300 people, but the patients who took the drug fared no better than those receiving a placebo. Meanwhile, ziltivekimab, which aimed to lower inflammation in patients with advanced kidney disease and high inflammatory levels, also failed to surpass placebo results in a trial involving 6,376 patients.

The findings surprised researchers who had viewed both treatments as potential breakthroughs. Dr. Karol Watson, director of UCLA’s preventive cardiology program, described the results as a major disappointment for the cardiovascular field. The data revealed no patient subgroup gained any benefit, prompting experts to question whether reducing Lp(a) or inflammation alone can effectively treat heart disease.

Dr. Paul Ridker, who led the ziltivekimab trial, had initially believed the approach held strong promise. After the results, he admitted the strategy had completely failed, with the drug offering no advantage to any participant. Dr. Steven Nissen, the pelacarsen trial’s lead investigator, concurred, stating there was no evidence the drug worked at all.

Scientists now must address why these two drugs, which altered key biological targets, did not lead to clinical improvements. The failures may require a broader review of how Lp(a) and inflammation influence heart disease—or whether addressing them individually is not enough. For patients in need of new treatments, the field remains without recent progress.

Both trials were designed to test whether targeting these specific pathways could lower cardiovascular risk. Pelacarsen’s inability to reduce events despite drastically lowering Lp(a) suggests the marker’s role may be more complex than previously understood. Similarly, ziltivekimab’s results indicate that inflammation alone might not be the sole driver of heart disease progression in these patient groups.