“Iedereen op de wereld, ikzelf inbegrepen, dacht dat dit zou werken.”
That was the stark admission from Dr. Steven Nissen of the Cleveland Clinic on Saturday, November 8, 2026, when he presented results for an experimental heart drug, pelacarsen, at the American Heart Association conference in Chicago. The news was that two highly anticipated experimental cardiovascular medications have failed in large-scale clinical trials, leaving cardiologists stunned.
Pelacarsen Performs No Better than Placebo in Heart Trials
The failures involve two distinct drugs targeting different biological pathways. Pelacarsen, from pharmaceutical giant Novartis, was tested on more than 8,300 patients with heart problems for more than 4.5 years. The trial results showed it performed no better than a placebo in preventing new heart attacks or strokes. Nissen summarized the finding bluntly: “Het deed niets. Het effect was compleet neutraal”, zei hij in een interview met persagentschap Reuters.
The setback was compounded by the simultaneous release of data for ziltivekimab, developed by Novo Nordisk. In a study of 6,300 patients, this experimental drug failed to reduce the risk of death for heart patients, nor did it lower their risk of heart attacks or strokes. Preliminary results from several months ago had already indicated that the two experimental drugs were underperforming and that further research was no longer useful.
What makes these results particularly jarring is that the drugs demonstrably succeeded in their intended biological actions. Pelacarsen successfully and drastically lowered Lp(a) concentrations in the blood, a protein in the blood that is thought to cause heart attacks and strokes.
Similarly, ziltivekimab effectively reduced inflammation in patients, a process thought to be central to the formation of artery-clogging plaques. Despite these measurable biochemical successes, the clinical outcomes for patients remained unchanged.
Pelacarsen and Ziltivekimab Fail to Provide Clinical Benefits
- Novartis and Novo Nordisk have suffered clinical trial setbacks with their experimental heart drugs, pelacarsen and ziltivekimab, respectively.
- Both drugs achieved their biological targets (lowering Lp(a) and reducing inflammation) but failed to translate into any clinical benefit for patients in large-scale trials.
- The failures cast doubt on foundational theories about the causes of heart attacks and strokes.
Questioning Core Medical Hypotheses
The first, the “inflammation hypothesis,” posits that chronic inflammation in blood vessels is a key role in the deposition of plaques in the arteries. Ziltivekimab was designed to test this by suppressing inflammation. The second, the “Lp(a) hypothesis,” holds that increased amounts of lipoprotein(a) can cause heart attacks and strokes. Pelacarsen was created to target Lp(a).
Pelacarsen slashed Lp(a) levels but did not reduce cardiovascular risk. Ziltivekimab tamed inflammation but did not prevent cardiac events. The logical conclusion, as Paul Ridker of the Brigham and Women’s Hospital of Harvard suggested, is that the drugs may have been tested on the wrong patient population.
Perhaps by the time patients in the studies had an initial cardiac event, the disease process was too advanced for these interventions to have an effect.
Researchers Call for Different Approaches Following Trial Failures
The trial failures represent a development for Novartis and Novo Nordisk.
Dr. Donald Lloyd-Jones, a professor of cardiology at Boston University who was not involved in the studies, called for a continued, multi-pronged approach to research. “Het is duidelijk dat we bijkomende studies nodig hebben, met verschillende middelen en verschillende benaderingen.”
The failures do not necessarily mean the underlying hypotheses are entirely wrong. Nissen, who led the study into pelacarsen, noted that the drug was tested on people who had already experienced a serious cardiovascular incident. Other ongoing studies are testing Lp(a)-lowering agents on individuals who have never had a heart attack or stroke. The outcome of those trials could determine future treatment standards.
| Drug | Developer | Target | Trial Size | Outcome |
|---|---|---|---|---|
| Pelacarsen | Novartis | Lp(a) Protein | More than 8,300 patients | No reduction in heart attacks/strokes |
| Ziltivekimab | Novo Nordisk | Inflammation | 6,300 patients | No reduction in death, heart attacks, or strokes |
Cardiologists Grapple with Implications of Biological Target Failures
Cardiologists are now grappling with the implications. If these well-understood biological targets do not lead to clinical success, what does?
