Promising Cholesterol Drug Fails to Prevent Heart Attacks, Stroke
WHO:
CNN - Steven Nissen said, “I’m going to have to weather the gasp in the audience,” anticipating the reaction to the trial results; he also described the result as “uniformly expected to be favorable” before the study.
CNN - Nissen said he sees young women who have strokes in their 30s and whose only risk factor is high Lp(a), calling it “a pure genetic risk.”
CNN - Fatima Rodriguez said the trial was “such an important trial” and that negative trials can be more important than positive ones; she said its results could prompt researchers to reconsider whether they have the wrong marker, drug or patient population, or whether the theory that Lp(a) drives heart risk is misguided.
CNN - Karol Watson said universal testing had left people anxious while “we still tell them we have nothing to offer them”; she compared measuring Lp(a) to measuring homocysteine, for which there is no available intervention.
NBC News - Amanda Doran said Vanderbilt was “pretty invested” in the trial and that its failure “obviously hurts.”
NPR - Harlan Krumholz, a Yale University cardiologist, called the failed result “really jarring.”
NPR - Roger Blumenthal, a Johns Hopkins University cardiologist, said treatment might need to start earlier or last longer.
NPR - David Maron, a Stanford University cardiologist and president of the American Society for Preventive Cardiology, suggested the trial may have needed a higher Lp(a) threshold for participation.
CNN - Dr. Steven Nissen, a preventive cardiologist at Cleveland Clinic in Ohio, led the study of pelacarsen and said, “It wasn’t a near miss. It just didn’t have an effect on outcomes.”
NBC News - Nissen was identified as chief academic officer of Cleveland Clinic’s Heart, Vascular & Thoracic Institute and said the results took him by “extreme surprise.”
CNN - Dr. Fatima Rodriguez, Stanford University’s chief of preventive cardiology, was not involved in the research and said, “There is no signal.”
CNN - Dr. Karol Watson, a UCLA cardiologist and professor, questioned the value of universal Lp(a) screening when no treatment specifically addresses high Lp(a).
NBC News - Watson, co-director of UCLA’s Program in Preventive Cardiology, said she had expected the drug to be “a slam dunk.”
CNN - Dr. Anurag Mehta, a cardiologist with Emory Healthcare and Lp(a) expert, said testing can help people understand risk and steps to control it.
NBC News - Dr. John Wilkins of Northwestern Medicine and Northwestern University’s Feinberg School of Medicine said Lp(a) remains a robust cardiovascular-risk marker.
NBC News - Dr. Amanda Doran, Vanderbilt University Medical Center assistant professor of medicine, said, “I’m still so hopeful. We’re going to get it in the end.”
CNN - Novartis developed pelacarsen and decided to abandon it. Eli Lilly, Amgen and Silence Therapeutics have other Lp(a)-lowering drugs in development or trials.
WHAT:
STAT - The HORIZON trial was a Phase 3 study; pelacarsen dramatically lowered Lp(a), but the trial found no difference in urgent coronary revascularization or deaths.
CNN - Nissen said the trial’s participants were older and may have been past the stage at which lowering Lp(a) could help; he also said treatment might be most beneficial before a first heart attack or stroke, as primary prevention.
CNN - Pelacarsen was Novartis-funded; the company had invested tens of millions of dollars in its development before deciding to abandon the drug.
CNN - Nissen said he plans to finish two ongoing trials of newer Lp(a)-lowering medications.
NPR - The study’s findings were also published in *NEJM Evidence*.
NPR - Cardiovascular disease kills more than 900,000 Americans each year.
NPR - Novartis said the study “provides meaningful evidence” about the relationship between Lp(a) and heart disease and may “help inform future approaches to cardiovascular management.”
CNN - Pelacarsen did not reduce major cardiovascular events despite lowering Lp(a) by an average of about 77%; roughly 12% of participants in each study group experienced a serious heart-related event.
NBC News - The Horizon trial found no decrease in heart attacks, strokes, cardiovascular deaths, or procedures to open blocked arteries or restore blood flow to the heart.
NBC News - Pelacarsen lowered Lp(a) by 78%, while placebo lowered it by 13%.
CNN - The trial’s MACE outcome included heart-related death, nonfatal heart attack or stroke, and urgent procedures such as bypass surgery.
CNN - Researchers reported no meaningful difference after examining outcomes by conditions such as diabetes or by individual cardiovascular events.
NBC News - The study results were published in the New England Journal of Medicine.
WHERE:
NPR - Nissen presented the study’s initial details at an American Heart Association meeting in Chicago.
CNN - Nissen’s study was presented at the American Heart Association’s annual conference.
NBC News - Vanderbilt was one of nearly 800 sites in the Horizon clinical trial.
WHEN:
CNN - The trial followed most participants for nearly five years.
NBC News - Participants were followed for an average of five years; the average age was 60.
WHY:
CNN - Nissen suggested that participants’ age, well-controlled LDL cholesterol, or a need to lower Lp(a) by 90% to 95% could explain the lack of benefit.
CNN - Nissen proposed that participants’ LDL cholesterol may have been well controlled, reducing the remaining risk associated with high Lp(a); he also said pelacarsen might have needed to lower Lp(a) by 90% to 95% to reduce heart risk.
NBC News - Karol Watson suggested that participants’ aggressive LDL and blood-pressure treatment, and possible aspirin use after prior heart attacks or strokes, may have reduced the remaining Lp(a)-associated risk.
NPR - Experts raised the possibility that the drug failed because participants’ blood pressure and LDL cholesterol were already well controlled.
CNN - Researchers had expected benefit because high Lp(a) is associated with increased cardiovascular risk; people with the highest levels have been reported to be two to four times more likely to have a heart attack than those with the lowest levels.
NBC News - About 1 in 5 Americans have high Lp(a), which is inherited; diet and exercise do not lower its levels.
HOW:
CNN - Nissen said exercise, weight loss, and statins to lower LDL cholesterol as much as possible should be part of preventive care for people with high Lp(a).
NBC News - Pelacarsen is an antisense oligonucleotide; other investigational injectable drugs use small interfering RNA (siRNA) and may cause fewer side effects, including injection-site reactions.
CNN - The study randomly assigned 8,350 people with high Lp(a) and a previous cardiovascular event to pelacarsen or placebo; patients and investigators did not know assignments.
NBC News - Horizon included 8,322 people with high Lp(a) who had experienced a heart attack, stroke or other heart problem within the prior 10 years.
CNN - Pelacarsen interferes with the body’s production of Lp(a); the article says exercise, weight loss and statins to lower LDL cholesterol are available risk-management measures.
NBC News - Other investigational treatments include lepodisiran, olpasiran and zerlasiran, which block liver production of Lp(a); muvalaplin is an oral drug under study, and CRISPR gene editing is in early development.
(UPDATED November 8, 2026 14:56 UTC)
Pelacarsen sharply lowered Lp(a), but a major trial found no reduction in heart events. Novartis is abandoning the drug after the disappointing results surprised researchers and cardiologists. Experts say treatment timing, patient selection, or already-controlled cholesterol may help explain the failure.
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(UPDATED November 8, 2026 06:57 UTC)
Novartis is abandoning pelacarsen after the drug failed to prevent major cardiovascular events. The treatment lowered harmful Lp(a) by roughly 78%, but heart-related outcomes were unchanged. Doctors say the disappointing result leaves prevention strategies and other experimental treatments under scrutiny.
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(UPDATED November 7, 2026 18:57 UTC)
Novartis’s pelacarsen sharply lowered Lp(a), but failed to prevent serious cardiovascular events. The disappointing trial result surprised cardiologists, despite Lp(a)’s established link to heart risk. Novartis abandoned the drug, while other Lp(a)-lowering treatments remain under development.
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(UPDATED November 7, 2026 15:59 UTC)
Pelacarsen sharply lowered Lp(a), but failed to reduce major cardiovascular events in a large trial. About one in five Americans has high, inherited Lp(a), linked to elevated heart risk. Novartis abandoned pelacarsen, while other Lp(a)-lowering treatments remain in development.