CHICAGO, Illinois: Two experimental heart disease treatments developed by Novartis and Novo Nordisk failed to prevent major cardiovascular complications despite successfully targeting the biological factors they were designed to address, raising questions among researchers about promising approaches to treating heart disease.

Detailed findings from both trials were presented on November 7 at the American Heart Association meeting in Chicago, revealing disappointing results for drugs targeting a genetic risk factor and inflammation.

Novartis' experimental drug pelacarsen reduced levels of lipoprotein(a), commonly known as Lp(a), by 78 percent but failed to prevent recurrent heart attacks, strokes or emergency procedures to unblock arteries in a study involving more than 8,300 patients.

The trial also found no reduction in deaths or non-fatal heart attacks.

"Everybody in the world, me included, thought that this was going to work," said Dr. Steven Nissen of the Cleveland Clinic, who presented the findings.

Novartis and its development partner Ionis Pharmaceuticals announced in September that pelacarsen had failed to meet the trial's primary goal, but researchers had been awaiting detailed results to determine whether the treatment offered any benefit.

"It didn't do anything. It was completely neutral," Nissen said.

Lp(a) is a genetically determined cardiovascular risk factor estimated to affect approximately 20 percent of the world's population. There are currently no approved treatments specifically for people with elevated Lp(a), and many affected individuals are unaware of their condition.

Researchers had hoped that reducing Lp(a) would lower cardiovascular risks, much as statins reduce heart attacks and strokes by lowering LDL, or bad cholesterol.

Patients in the pelacarsen trial received either a monthly 70-milligram dose of the drug or a placebo and were followed for a median of 4.7 years.

All participants had previously experienced a major cardiovascular event, and other risk factors, including high LDL cholesterol and blood pressure, were carefully controlled.

Nevertheless, the treatment produced no meaningful cardiovascular benefit. Some 20.6 percent of patients receiving pelacarsen discontinued treatment because of adverse effects, compared with 7.5 percent in the placebo group.

Additional statistical analyses, including assessments of patients with greater reductions in Lp(a), also found no benefit.

The findings were published in the New England Journal of Medicine, with further analysis appearing in NEJM Evidence.

However, researchers cautioned against abandoning efforts to target Lp(a).

Dr. Donald Lloyd-Jones, a cardiology professor at Boston University, said more evidence from different patient populations was needed before rejecting Lp(a) as a cause of heart disease or a potential treatment target.

Other experimental drugs, including Amgen's olpasiran and Eli Lilly's lepodisiran, use a different technology known as small interfering RNA and have reduced Lp(a) levels by approximately 95 percent.

Pelacarsen instead uses antisense oligonucleotide technology to reduce production of proteins associated with faulty genes.

Nissen said the alternative treatments may produce different results, particularly because their trials include more patients who have never suffered a heart attack or stroke.

He also noted that the newer drugs have demonstrated greater effectiveness in lowering Lp(a) and better tolerability.

"Whether that will translate into better outcomes remains to be seen."

Amgen's Phase 3 trial results are expected in early 2028, while Lilly's are anticipated in 2029.

Meanwhile, Novo Nordisk's experimental anti-inflammatory drug ziltivekimab also failed to reduce major cardiovascular events despite successfully lowering inflammation.

The Danish drugmaker's trial involved approximately 6,300 patients with heart disease, advanced kidney disease and systemic inflammation.

Ziltivekimab was designed to neutralize interleukin-6, a major contributor to inflammation in high-risk heart patients.

Although the treatment reduced inflammation, it did not lower the risk of death, heart attacks or strokes compared with a placebo.

Novo Nordisk announced the trial's failure in July. The setback weakened its prospects of expanding beyond its successful GLP-1 diabetes and obesity drug businesses.

On September 7, the company discontinued two additional late-stage ziltivekimab trials involving patients with heart failure and inflammation after an independent monitoring committee determined they were unlikely to succeed.

Dr. Paul Ridker of Harvard's Brigham and Women's Hospital, who presented the ziltivekimab findings, suggested that the patients' disease may have been too advanced for anti-inflammatory treatment to provide a meaningful benefit.

Dr. Priscilla Hsue of UCLA, who was not involved in the study, similarly noted that the participants were seriously ill and that inflammation may already have caused irreversible harm.

Despite the disappointing results, researchers said the underlying treatment approaches warranted further investigation.

"It's clear we need further trials using different compounds and different strategies," Lloyd-Jones said.