{"id":97649,"date":"2026-11-09T00:01:00","date_gmt":"2026-11-09T07:01:00","guid":{"rendered":"https:\/\/www.opinionpublica.tv\/portada\/?p=97649"},"modified":"2026-11-08T19:53:39","modified_gmt":"2026-11-09T02:53:39","slug":"doctors-absorb-the-stunning-failure-of-two-high-profile-heart-drugs","status":"publish","type":"post","link":"https:\/\/www.opinionpublica.tv\/portada\/doctors-absorb-the-stunning-failure-of-two-high-profile-heart-drugs\/","title":{"rendered":"Doctors absorb the stunning failure of two high-profile heart drugs"},"content":{"rendered":"\n
\"Doctors<\/figure>\n\n\n\n

Cardiologists have been on edge for months, waiting for the details surrounding recent reports of the stunning failures of two new heart drugs.<\/p>\n\n\n\n

The drugs \u2014 pelacarsen and ziltivekimab \u2014 were widely expected to usher in a new era in preventing heart disease. Companies, betting on the drugs\u2019 promise, made huge investments in developing them.<\/p>\n\n\n\n

So when doctors saw preliminary announcements that the drugs were not helping patients in large clinical trials, many felt blindsided, although still hopeful that there was more to the story than they knew.<\/p>\n\n\n\n

\u201cThe whole cardiovascular community was gobsmacked,\u201d said Dr. Karol Watson, a director of UCLA\u2019s preventive cardiology program.<\/p>\n\n\n\n

Were the drugs close to succeeding, just barely missing a statistically significant benefit? Or were there at least subgroups of patients who were helped?<\/p>\n\n\n\n

Now the answers are in. There was not a shred of evidence that the drugs helped anyone. By every measure, they were no better than placebos.<\/p>\n\n\n\n

The results, Dr. Watson noted, \u201care about as neutral as they can be.\u201d The full data were presented on Saturday morning at the annual meeting of the American Heart Association and in simultaneous publications in The New England Journal of Medicine.<\/p>\n\n\n\n

One drug, pelacarsen, by Novartis, is known to make levels of the Lp(a) blood protein plunge. The protein is widely believed to cause heart attacks and strokes. The other, ziltivekimab, by Novo Nordisk, stops inflammation, thought to be a major component of plaques in arteries. Neither drug made a dent in heart disease outcomes during these clinical trials.<\/p>\n\n\n\n

Dr. Paul Ridker of Mass General Brigham, who was the principal investigator for the inflammation trial \u2014 known as the Zeus study \u2014 had been a true believer.<\/p>\n\n\n\n

He was convinced by suggestive evidence that squelching inflammation could protect people from heart disease. There was, he said, an earlier encouraging study involving an experimental anti-inflammatory drug made by Novartis, as well as studies indicating that colchicine, an anti-inflammatory drug used to treat gout, could also be protective.<\/p>\n\n\n\n

Until the day he saw the results, Dr. Ridker said in a recent interview, he had thought the Zeus study was \u201ca brilliant idea,\u201d bound to show that the Novo drug, ziltivekimab, which blocks an inflammatory protein called il-6, was effective. The participants all had severe heart disease, advanced kidney disease and a blood protein that is a marker of inflammation.<\/p>\n\n\n\n

Instead of protecting patients in Zeus, though, Dr. Ridker announced on Saturday that no one had been helped by the drug. Every subgroup of patients in the 6,376-patient study fared the same. Those taking the drug did no better than those taking a placebo, even though the drug did reduce inflammation.<\/p>\n\n\n\n

\u201cDid we pick the wrong target, the wrong patient population?\u201d Dr. Ridker said.<\/p>\n\n\n\n

Or did the patients have heart disease that was so advanced it could not be helped? \u201cMaybe the horse was out of the barn,\u201d he said.<\/p>\n\n\n\n

Others in the field are wondering if the hypothesis itself was wrong. Maybe inflammation is a sign of disease, not a cause, as white hair is a sign of aging.<\/p>\n\n\n\n

He was convinced by suggestive evidence that squelching inflammation could protect people from heart disease. There was, he said, an earlier encouraging study involving an experimental anti-inflammatory drug made by Novartis, as well as studies indicating that colchicine, an anti-inflammatory drug used to treat gout, could also be protective.<\/p>\n\n\n\n

Until the day he saw the results, Dr. Ridker said in a recent interview, he had thought the Zeus study was \u201ca brilliant idea,\u201d bound to show that the Novo drug, ziltivekimab, which blocks an inflammatory protein called il-6, was effective. The participants all had severe heart disease, advanced kidney disease and a blood protein that is a marker of inflammation.<\/p>\n\n\n\n

Instead of protecting patients in Zeus, though, Dr. Ridker announced on Saturday that no one had been helped by the drug. Every subgroup of patients in the 6,376-patient study fared the same. Those taking the drug did no better than those taking a placebo, even though the drug did reduce inflammation.<\/p>\n\n\n\n

\u201cDid we pick the wrong target, the wrong patient population?\u201d Dr. Ridker said.<\/p>\n\n\n\n

Or did the patients have heart disease that was so advanced it could not be helped? \u201cMaybe the horse was out of the barn,\u201d he said.<\/p>\n\n\n\n

Others in the field are wondering if the hypothesis itself was wrong. Maybe inflammation is a sign of disease, not a cause, as white hair is a sign of aging.<\/p>\n\n\n\n

Novo announced in September that it was stopping two other studies of ziltivekimab that involved patients with heart failure. An independent committee determined that the drug was not helping them. The company is continuing to test its drug in patients who have had a heart attack. That study will conclude next year.<\/p>\n\n\n\n

Dr. Ridker, who proposed the link between inflammation and heart disease more than a quarter-century ago, has not given up hope. He noted that there was genetic and epidemiological evidence as well as evidence from animal studies that a different protein in the same inflammation pathway should protect against heart attacks and strokes.<\/p>\n\n\n\n

\u201cWe already know this is going to work,\u201d Dr. Ridker said. Now, he added, the question is: \u201cHow do we find the right drug for the right patient?\u201d<\/p>\n\n\n\n

The principal investigator for Horizon, the Lp(a) study, is Dr. Steven Nissen of the Cleveland Clinic. He said his concern was that the study\u2019s disappointing results would lead patients to drop out of two other studies testing drugs that reduce Lp(a) levels.<\/p>\n\n\n\n

\u201cA single trial doesn\u2019t necessarily give us all the answers,\u201d Dr. Nissen said. And, he added, high levels of Lp(a) are \u201ca powerful risk factor.\u201d It remains possible, he said, that patients in the Horizon trial had heart disease so advanced that it was too late for the Novartis drug to help.<\/p>\n\n\n\n

Another hypothesis was that the patients\u2019 other risk factors \u2014 blood pressure and L.D.L. cholesterol \u2014 were so well controlled that their risk was about as low as it could go, said Dr. Roger Blumenthal, director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. Reducing Lp(a) levels could not lower it further.<\/p>\n\n\n\n

Dr. Ridker had another idea. All the Horizon patients were taking anti-clotting medications. Lp(a) is thought to cause heart disease by promoting blood clots. Perhaps the anti-clotting medications diluted the drug\u2019s effects.<\/p>\n\n\n\n

But the bottom line was that, for whatever reasons, the Novartis drug had utterly failed.<\/p>\n\n\n\n

\u201cWas there anything that we could point a finger to that said, \u2018Yeah, there\u2019s a benefit\u2019?\u201d Dr. Nissen asked.<\/p>\n\n\n\n

No, he added, \u201cthere was nothing.\u201d<\/p>\n\n\n\n