Curated News
By: NewsRamp Editorial Staff
November 07, 2026
Pelacarsen Slashes Lp(a) by 78% but Fails to Cut Cardiovascular Events
TLDR
- Pelacarsen cut Lp(a) by 78% but failed to reduce cardiovascular events, signaling a setback for Novartis and a potential opening for rival Lp(a) therapies.
- The Lp(a) HORIZON trial randomized 8,323 adults with cardiovascular disease across 42 countries to monthly pelacarsen or placebo and found no difference in major adverse cardiovascular events despite a 78% Lp(a) reduction.
- Despite neutral results, the trial underscores that measuring Lp(a) helps identify hidden cardiovascular risk and empowers people to take preventive action for longer, healthier lives.
- A monthly injection that lowered Lp(a) by 78% unexpectedly failed to prevent heart attacks or strokes, revealing that Lp(a) is a risk marker but not yet a proven treatment target.
Impact - Why it Matters
This news matters because it challenges the assumption that lowering Lp(a) will automatically reduce cardiovascular risk, a belief that has driven decades of research and drug development. With no FDA-approved therapy for elevated Lp(a) yet, patients and clinicians must continue to rely on aggressive management of traditional risk factors like LDL cholesterol and blood pressure. The trial’s neutral results also underscore the need for more research into Lp(a)’s mechanisms and interactions, and highlight the importance of measuring Lp(a) to refine risk assessment. For the millions with high Lp(a), the findings may be disappointing but not definitive—other Lp(a)-lowering drugs are in late-stage testing, and the journey to find effective treatments continues.
Summary
Results from the Lp(a) HORIZON trial, presented at the American Heart Association’s Scientific Sessions 2026 and simultaneously published in The New England Journal of Medicine and NEJM Evidence, reveal a puzzling paradox: the novel drug pelacarsen dramatically lowered Lp(a) levels by 78% but failed to reduce major adverse cardiovascular events (MACE). The 7-year, phase III, multicenter trial enrolled more than 8,300 adults with established cardiovascular disease and elevated Lp(a) (≥70 mg/dL) across 42 countries. Participants received monthly injections of pelacarsen or placebo. Despite the substantial Lp(a) reduction, there was no change in the time to nonfatal heart attack, stroke, urgent revascularization, or cardiovascular death, even in a subgroup with Lp(a) ≥90 mg/dL. “I cannot avoid the disappointing conclusion – it didn’t work,” said Steven E. Nissen, M.D., senior author and chief academic officer of the Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. “The neutral finding was unexpected and surprising to the medical community.”
Nissen emphasized that the results do not mean Lp(a) is irrelevant. “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.” He urged patients in ongoing Lp(a) trials not to drop out and stressed that measuring Lp(a) remains worthwhile. “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.” The trial, funded by Novartis, had limitations including a predominantly white population and potential COVID-19-related events. Three other cardiovascular outcome trials for different Lp(a)-lowering compounds are underway, which Nissen hopes will provide a clearer picture. The 2026 multi-society guideline on the management of dyslipidemia recommends Lp(a) measurement at least once in adulthood, and about 1 in 5 people globally have elevated Lp(a).
Source Statement
This curated news summary relied on content distributed by NewMediaWire. Read the original source here, Pelacarsen Slashes Lp(a) by 78% but Fails to Cut Cardiovascular Events
