Lp(a) treatment is now being tested in people who have not yet had a heart attack
Table of Contents
1.0 Summary
Lipoprotein(a) is an inherited risk factor for heart disease and for narrowing of the aortic valve, and diet, exercise, statins and PCSK9 drugs barely touch it. Five drugs designed to lower it are now in late-stage testing, cutting blood levels by roughly 80 percent to 96.4 percent, and a review published in August 2026 puts the first hard outcome result, from the pelacarsen trial Lp(a) HORIZON, in late 2026. What changed in August is how far the testing now reaches. Amgen has started recruiting 11,000 adults with high Lp(a) who have not yet had a cardiovascular event, Lilly is recruiting 10,450 into a phase 3 trial of the oral drug muvalaplin, a smaller Lilly trial is using CT angiography to see whether lepodisiran changes coronary plaque itself, and Merck has begun testing a new Lp(a) drug alongside the oral PCSK9 inhibitor approved in July. None of these drugs is approved, and none has yet been shown to prevent a heart attack.
2.0 Key Points
- Lp(a) levels are 70 to 90 percent inherited, change little with lifestyle, and are not meaningfully lowered by statins or PCSK9 inhibitors.
- Five drugs are in late-stage development, lowering Lp(a) by about 80 percent with pelacarsen up to 96.4 percent with zerlasiran; a single dose of lepodisiran held a 93.9 percent reduction for more than 12 months.
- The first cardiovascular outcome results, from the pelacarsen trial Lp(a) HORIZON, are expected in late 2026.
- Amgen has begun recruiting 11,000 adults with high Lp(a) who have not yet had a cardiovascular event into OCEAN(a)-PreEvent, testing whether olpasiran prevents coronary death, heart attack or urgent revascularization.
- No Lp(a)-lowering drug is approved, and no trial has yet reported that lowering Lp(a) reduces cardiovascular events.
3.0 Evidence base
Lipoprotein(a), usually written Lp(a), is an LDL particle carrying an extra protein called apolipoprotein(a). How much of it circulates is set mostly by one gene. Levels are 70 to 90 percent heritable, they move very little with diet or exercise, and statins and PCSK9 inhibitors leave them roughly where they were. High Lp(a) raises the risk of atherosclerotic cardiovascular disease and of calcific aortic valve stenosis, the stiffening and narrowing of the aortic valve [1].
A review in Current Atherosclerosis Reports, which worked through phase 1 to 3 trial data, regulatory updates and trial registries up to mid-2026, counts five drugs in late-stage development using three different approaches [1]. Pelacarsen is an antisense oligonucleotide, an engineered strand of genetic material that tells liver cells to make less apo(a). It lowers Lp(a) by about 80 percent, and its phase 3 trial, Lp(a) HORIZON, is due to report in late 2026. Three small interfering RNA drugs interrupt the same production step by a different route and go further: olpasiran by more than 95 percent, zerlasiran by 96.4 percent, and lepodisiran by 93.9 percent, with a single dose holding that reduction past 12 months. That durability is what makes dosing every three months, or possibly once a year, plausible. Muvalaplin works differently again. It is a tablet, and it stops the apo(a) and apoB components from assembling into an Lp(a) particle at all; in the phase 2 KRAKEN program it cut intact Lp(a) by up to 85.8 percent. Gene editing has entered the field as well, with CTX320, a CRISPR therapy aimed at the LPA gene in the liver, now in phase 1. Safety has looked acceptable for all of them so far [1].
All of those figures are blood levels. Whether moving them prevents heart attacks is the question the outcome trials exist to answer.
4.0 What changed in August
Four trial registrations posted in August 2026 show where the testing is going.
Amgen has started recruiting OCEAN(a)-PreEvent, a phase 3 trial of olpasiran against placebo in about 11,000 adults who have high Lp(a) and are at risk of a first major cardiovascular event. The endpoint is death from coronary heart disease, heart attack, or urgent coronary revascularization [2]. This is primary prevention. The trial is enrolling people who have not had an event yet, which is a harder question than preventing a second one and needs a much bigger trial to answer.
Lilly is recruiting 10,450 adults into a phase 3 trial of muvalaplin, in people with high Lp(a) who either already have cardiovascular disease or are at risk of a heart attack or stroke [3]. The review refers to muvalaplin’s phase 3 outcome trial as MOVE-Lp(a) [1].
A smaller Lilly trial, 252 people followed for about 120 weeks, asks a narrower question: does lepodisiran change the amount and the type of plaque in the coronary arteries, measured by CT angiography, in people with high Lp(a) who have had a cardiac event or are at high risk [4]. Plaque on a scan is still a stand-in for a clinical event, but it is a closer one than a laboratory value.
Merck has a phase 2 trial of 750 people testing MK-7262, a new Lp(a)-lowering agent, on its own and in combination with enlicitide, the oral PCSK9 inhibitor the FDA approved in July 2026 [5, 6]. Merck is measuring both Lp(a) and LDL cholesterol against placebo, with each drug alone and with the two together [5]. An all-oral regimen covering both particles would be a different proposition for patients than an injection for each.
5.0 Where it fits in practice
None of this changes what can be prescribed today. No Lp(a)-lowering drug is approved [1].
What it strengthens is the case for measuring. Current guidelines recommend checking Lp(a) once in every adult, and that recommendation was written in anticipation of treatment arriving [1]. A patient whose level is known now is a patient who can be offered a trial, and who can be found quickly if the outcome trials read out positive.
The measurement protocol used on this site, including units and when to repeat the test, is in /clinical/06-advanced-tools.html. How an elevated result feeds into an individual risk estimate is in /clinical/04-risk-stratification.html. For someone with high Lp(a) today the practical response has not changed: lower every other risk factor that can be lowered, as laid out in /clinical/05-treatment-pathways.html.
6.0 Open questions
The central question is still open. No trial has reported that lowering Lp(a) prevents cardiovascular events [1]. The case for treating it rests on genetics and epidemiology, which point consistently in one direction but are not a randomized result. Lp(a) HORIZON, expected late in 2026, is the first real test, and a negative result would carry as much weight as a positive one.
The four trials described above have registered protocols and no results [2, 3, 4, 5]. A registry entry records what a sponsor intends to measure and how many people it plans to enroll. It says nothing about what will be found, and trials of this size take years to finish.
The pipeline percentages come from a narrative review rather than from the primary trial publications [1]. They are drawn from published phase 1 to 3 data, but a review is a secondary summary, and the dose, population and duration behind each figure sit in the original papers.
This summary is provided for clinical decision support only and does not replace individualized clinical judgment. Findings are summarized from the cited primary sources; consult those sources before changing practice.
Version History
| Version | Date | Description |
|---|---|---|
| 1.0.0 | 2026-08-23 | Initial release |
References
- Ebubechukwu U et al. Novel Lipoprotein (a) Therapies: A Comprehensive Review. Current atherosclerosis reports. 2026-08-13. doi:10.1007/s11883-026-01453-9. Available at: https://doi.org/10.1007/s11883-026-01453-9
- OCEAN(a)-PreEvent - Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction to Prevent First Major Cardiovascular Events. ClinicalTrials.gov. 2026-08-13. https://clinicaltrials.gov/study/NCT07136012.
- Assessing the Impact of Muvalaplin on Major Cardiovascular Events in Adults With Elevated Lipoprotein(a). ClinicalTrials.gov. 2026-08-21. https://clinicaltrials.gov/study/NCT07157774.
- A Study to See if Lepodisiran Can Reduce Plaque in Coronary Arteries of Adults With Elevated Lp(a) Who Have Had Heart Events or Are at High Risk. ClinicalTrials.gov. 2026-08-21. https://clinicaltrials.gov/study/NCT07613294.
- A Clinical Trial of MK-7262 and Enlicitide in Participants With High Lipoprotein(a) (MK-7262-004). ClinicalTrials.gov. 2026-08-17. https://clinicaltrials.gov/study/NCT07614984.
- FDA Approves First Oral PCSK9 Inhibitor to Lower LDL Cholesterol in Adults with High Cholesterol. 2026-07-17. http://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-pcsk9-inhibitor-lower-ldl-cholesterol-adults-high-cholesterol.