By: NewMediaWire
November 7, 2026

Curated TLDR

Lp(a) HORIZON Trial: Lp(a) Fell By 78%, But Cardiovascular Outcomes Unexpectedly Neutral

Research Highlights:

  • In the 7-year, phase III, multicenter, international Lp(a) HORIZON trial, the novel medication pelacarsen lowered Lp(a) levels by a mean of 78% in a trial with more than 8,300 adults with cardiovascular disease in 42 countries.
  • However, even with a significant reduction in Lp(a) levels while taking pelacarsen, there was no change in the time to occurrence of a major adverse cardiovascular event (MACE), defined in this trial as nonfatal heart attack, stroke, an urgent revascularization procedure to open clogged heart arteries or death from any cardiovascular cause.
  • While this trial was not successful in improving CVD outcomes, the researchers urge everyone to have their Lp(a) levels measured to help estimate their CVD risk and to enable them to take action to reduce their risk and prevent a major cardiovascular event.
  • Results of the Lp(a) HORIZON trial, Primary vs. Extended, presented at the American Heart Association’s Scientific Sessions 2026, are simultaneously published in The New England Journal of Medicine and NEJM Evidence, respectively.

Embargoed until 8:50 am CT/9:50 am ET, Sat., Nov. 7, 2026

This news release includes additional data and findings from the research author.

CHICAGO, ILLINOIS - November 7, 2026 (NEWMEDIAWIRE) - In the 7-year, phase III, multi-center, international clinical trial called Lp(a) HORIZON, the novel compound pelacarsen reduced Lp(a) levels by 78% in adults with elevated Lp(a) and established cardiovascular disease. However, there was no change in time to nonfatal heart attack, stroke, urgent revascularization procedure to open clogged heart arteries, death from any cardiovascular cause, death from coronary heart disease or death from any cause, according to the primary and extended analyses of the Lp(a) HORIZON trial, a Late-Breaking Science presentation today at the American Heart Association’s Scientific Sessions 2026. The meeting on Nov. 6-9 in Chicago is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.

More than 8,300 adults with established cardiovascular disease and high Lp(a) measures (≥70 mg/dL) in 42 countries were enrolled in Lp(a) HORIZON. At enrollment, participants were assigned to 30-90 days of treatment for CVD risk factors (if required) to meet current guidelines including high cholesterol and high blood pressure. Participants were randomly assigned to receive either pelacarsen or placebo as a monthly injection under the skin, with Lp(a) levels measured annually.

The amount of time to the first occurrence of either nonfatal heart attack, stroke, urgent revascularization procedure to clear clogged heart arteries, or death from any cardiovascular cause was measured and compared across participants in the primary group (Lp(a) levels at 70 mg/dL or higher) and a subgroup of participants with Lp(a) of 90 mg/dL or higher. In addition, the effect of pelacarsen on Lp(a) was analyzed in the entire group, and the subgroup with Lp(a) of 90 mg/dL or higher, representing the highest 15% of people worldwide with elevated Lp(a). Extended analyses were also conducted for data on all participants to assess time to occurrence of 4 additional combinations of CVD outcomes: 1) heart attack, stroke or death from any cardiovascular cause; 2) heart attack, urgent revascularization procedure to clear clogged heart arteries or death from coronary heart disease; 3) change in Lp(a) from enrollment to 1 year; and 4) death from any cause.

“I cannot avoid the disappointing conclusion – it didn’t work. Pelacarsen improved Lp(a) measures significantly – 78% lower; however, cardiovascular outcomes were unchanged . The neutral finding was unexpected and surprising to the medical community,” said Steven E. Nissen, M.D., FAHA, senior author of the new study and chief academic officer of the Miller Family Heart, Vascular & Thoracic Institute at the Cleveland Clinic in Cleveland, Ohio.

What are the study’s key findings?

  • Pelacarsen reduced Lp(a) significantly, by an average of 78% across all participant groups.
  • Participants had Lp(a) levels higher than 70 mg/dL (approximately 148 nmol/L), the highest 20% of the global population, and there was no difference in the amount of time before a patient experienced a major adverse cardiovascular event (MACE), the trial’s primary composite outcome described above.
  • There was still no change in any cardiovascular outcomes in the pelacarsen subgroup of patients with Lp(a) of 90 mg/dL (approximately ~192 nmol/L) or higher.
  • In the extended analyses, several secondary endpoints, including deaths from any cause and other CVD outcomes, were evaluated separately, in different combinations and among various participant subgroups. Outcomes were consistent and unchanged between the pelacarsen and placebo groups across all of them.

“The results were completely neutral across multiple analyses. There was basically no effect on outcomes, not even a trend, even in subpopulations,” said Nissen. “However, this does not mean Lp(a) is irrelevant. It means we need more in-depth research to help us fully understand the underlying mechanisms of Lp(a), its interactions with other CVD risk factors and how it does or does not impact cardiovascular outcomes. So for anyone currently enrolled in an Lp(a) trial, don’t drop out because of these findings. Lp(a) is still an important piece of the overall cardiovascular disease puzzle, an important cause of morbidity and mortality worldwide.”

Lp(a), or lipoprotein a, is a form of cholesterol that has some characteristics in common with LDL cholesterol (low-density lipoprotein cholesterol, also known as “bad” cholesterol), including causing plaque to build up in arteries and reduce blood flow to the heart, brain, kidneys, legs and other parts of the body. Lp(a) levels are largely genetically determined and remain relatively stable over a lifetime. High Lp(a) (125 nmol/L or greater, or 55 mg/dL or higher) is associated with about a 1.4-fold increased long-term risk of heart attack or stroke. An Lp(a) of 250 nmol/L (or 115 mg/dL) is associated with at least a two-fold increased long-term risk of heart attack or stroke. Lifestyle changes, such as exercise and improved diet, have little impact on Lp(a) levels, and neither do medications that reduce “bad” cholesterol such as statins. Currently, there is no FDA-approved medication or treatment to lower Lp(a).

“Measuring Lp(a) is still absolutely worthwhile. Lp(a) is an important risk factor for CVD, and high levels of Lp(a) usually do not present with any symptoms. Lp(a) levels, along with blood pressure, cholesterol and blood sugar, are important measures that inform the CVD prevention and treatment options developed for each patient. Also important is guiding our patients to healthy lifestyle improvements. Proactive, healthier lifestyle habits for optimal cardiovascular health and treatment should be implemented as early as possible,” said Nissen. “Three other cardiovascular outcome trials are underway for other investigational compounds that target high Lp(a) in different ways than pelacarsen. I am eager to see the results of those trials in the next few years, and together with the results of Lp(a) HORIZON, we will hopefully have a more robust picture about lowering Lp(a) and its relationship to CVD outcomes.”

What are the study’s details, background, design and limitations?

  • Lp(a) HORIZON was conducted at 797 sites in 42 countries, starting in 2019 and ended in 2026. 14,249 adults were screened, and 8,323 adults (mean age of 60 years; 27% women; 26% had diabetes (almost all Type 2 diabetes)) with established cardiovascular disease (previous cardiovascular event within 3 months to 10 years before screening ) were enrolled to participate in the double-blind, randomized, placebo-controlled trial.
  • 82% had a previous heart attack; previous clot-caused stroke in 10%; poor blood flow in the legs causing symptoms in 14%; and multiple cardiovascular events in 18% . Heart attack or stroke at an early age (before age 55 in men and before age 65 in women) was documented in 37% of participants .
  • Lp(a) levels for all participants were 70 mg/dL (148 nmol/L) or higher; the median Lp(a) among all participants at enrollment was 109 mg/dL (236 nmol/L). A subpopulation of participants had Lp(a) levels at or above 90 mg/dL (192 nmol/L).
  • About 75% of participants were already meeting guideline criteria for blood pressure and cholesterol, therefore, they did not receive additional treatment. Nearly all participants were taking antiplatelet medications such as aspirin or other agents like clopidogrel, and 77-78% of participants were taking high-intensity statins.
  • Participants were randomly assigned to receive either a monthly injection under the skin of the Lp(a)-lowering medication pelacarsen (dose of 80 mg) or a placebo. Pelacarsen is a small segment of synthetic genetic material (like DNA) that enters liver cells and blocks production of Lp(a), thereby lowering Lp(a) levels.
  • The subgroups included participants with baseline Lp(a) above and below the median; LDL-C above and below the median; hs-CRP above and below the median; and time from qualifying cardiovascular event to baseline above and below the median. Patient characteristics were also analyzed across all participants to detail who had a cardiovascular event compared with those who did not.
  • While there were a similar number of serious adverse events among all participants reported over the 7-year study (37.3% in the pelacarsen group; 41.1% in the placebo group), there was notable greater incidence in pelacarsen treated patients of some adverse reactions, such as flu-like symptoms, injection site reactions and acute allergic reactions, between the treatment vs. placebo group. The most serious allergic reaction was anaphylaxis, in 19 patients receiving pelacarsen and none with placebo. No deaths due to these adverse allergic reactions occurred.
  • Overall, about 21% of patients in the pelacarsen group and more than 7% receiving placebo chose to stop taking their study medication because of adverse reactions .
  • The trial had several limitations. Launched in 2019 and ending in 2026, some of the participants’ cardiovascular events occurred during the COVID-19 pandemic and may have been COVID-related CVD events, which could not be determined. The majority of participants (78%) also self-identified as white, while less than 4% of participants were of African ancestry, a group with an average Lp(a) level that is 2 times higher than white people. The researchers note that future Lp(a) trials will need broader participant representation in order to assess safety and efficacy in various population groups, particularly groups known to have higher Lp(a) levels.

A high level of Lp(a) is a common independent risk factor for cardiovascular disease, as detailed in the 2026 multi-society guideline on the management of dyslipidemia, and the guideline recommends Lp(a) should be measured at least once in adulthood. About 1 in 5 people globally, approximately 1.4 billion, are thought to have elevated Lp(a) levels. Some people with elevated levels of Lp(a) plus other serious conditions, such as genetic disorders that raise bad cholesterol, are sometimes treated with apheresis—a dialysis-like treatment to remove harmful cholesterol from their blood.

Co-authors and disclosures are listed in the manuscript. The Lp(a) HORIZON trial was funded by Novartis.

Statements and conclusions of studies that are presented at the American Heart Association’s scientific meetings are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association’s scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

The Association receives more than 85% of its revenue from sources other than corporations. These sources include contributions from individuals, foundations and estates, as well as investment earnings and revenue from the sale of our educational materials. Corporations (including pharmaceutical, device manufacturers and other companies) also make donations to the Association. The Association has strict policies to prevent any donations from influencing its science content and policy positions. Overall financial information is available here.

Additional Resources:

About the American Heart Association

The American Heart Association is a relentless force for a world of longer, healthier lives. Dedicated to ensuring equitable health in all communities, the organization has been a leading source of health information for more than one hundred years. Supported by more than 35 million volunteers globally, we fund groundbreaking research, advocate for the public’s health, and provide critical resources to save and improve lives affected by cardiovascular disease and stroke. By driving breakthroughs and implementing proven solutions in science, policy, and care, we work tirelessly to advance health and transform lives every day. Connect with us on heart.org, Facebook, X or by calling 1-800-AHA-USA1.

For Media Inquiries and American Heart Association Expert Perspective:

American Heart Association Communications & Media Relations in Dallas: 214-706-1173; [email protected]

Michelle Kirkwood: [email protected]

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