Cholesterol, ApoB & Lp(a)
What Is Lipoprotein(a), or Lp(a), and What Do Testing Guidelines Say?
Lp(a) is a mostly inherited particle linked to heart attack, stroke and aortic stenosis. US guidance says every adult should be tested at least once.
Most standard cholesterol tests skip one particle entirely. It’s called lipoprotein(a), or Lp(a), pronounced “L-P-little-a”: a name that looks like a typo and a pronunciation almost nobody guesses on the first try. Humanic Blue starts with the particle itself before getting to what a result might mean.
What is lipoprotein(a), then? It’s an LDL-like, cholesterol-carrying particle with an extra protein attached. Your level is mostly inherited, diet and exercise barely move it, and a high level raises the risk of heart attack, stroke and a narrowed aortic valve even when the rest of your cholesterol looks ordinary. The 2026 US cholesterol guideline says every adult should have it measured at least once. For anyone thinking about living longer, one piece is still missing: no drug has yet been shown to turn a lower Lp(a) number into fewer heart attacks. The first large trial to test that missed its main goal in September 2026.
In This Article
- An inherited particle with an extra attachment
- Why one test is usually enough, and why relatives may need one too
- Read the unit before the number
- What counts as high, and what a high result does and doesn’t mean
- Lifestyle barely moves Lp(a), but the rest of the risk still counts
- The first big Lp(a)-lowering trial missed its goal
- The studies and numbers behind all of this
Key Takeaways
- Lp(a) is a mostly inherited, cholesterol-carrying particle. Genetic and population studies tie high levels to heart attack, stroke and aortic valve stenosis.
- The 2026 US guideline and the National Lipid Association recommend testing every adult at least once. A standard cholesterol panel doesn’t include it.
- Risk climbs gradually. The ACC reports about 1.4 times the long-term risk at the common US high threshold compared with the population median. The threshold is 125 nmol/L or 50 mg/dL, depending on the test’s units.
- Lifestyle barely changes the number, but managing LDL cholesterol, blood pressure, diabetes and smoking lowers overall risk.
- In September 2026, Novartis said its drug pelacarsen lowered Lp(a) but missed its phase 3 trial’s main goal of reducing heart events. Full results aren’t public yet; these drugs remain experimental.
An LDL-like particle with an extra attachment
Lp(a) starts as an LDL-like particle: cholesterol wrapped around one molecule of ApoB, the protein that marks cholesterol-carrying particles. A second protein, apolipoprotein(a), is bolted on. The size of that extra protein varies from person to person, because it can carry anywhere from 3 to more than 40 copies of one repeating segment, according to the National Lipid Association (NLA), the US society for cholesterol specialists. The LPA gene makes it. “Your level is mostly inherited,” as the American Heart Association puts it.
The case that Lp(a) causes disease, rather than just traveling with it, is well developed. The European Atherosclerosis Society’s 2022 consensus statement, written by 22 experts with first author Florian Kronenberg of the Medical University of Innsbruck, says genetic and population studies of hundreds of thousands of people strongly support a causal and continuous link between Lp(a) and cardiovascular outcomes, across ethnic groups. It adds that high Lp(a) is a risk factor even when LDL cholesterol is very low. Most of its authors report paid ties to drug companies, including makers of Lp(a)-lowering drugs. See the details
“Continuous” matters. Risk doesn’t switch on at one lab cutoff. Guidelines draw lines because clinicians need decision points, but the biology behaves more like a slope.
The NLA says the most consistent links are with heart attack and calcific aortic valve stenosis, a stiffening and narrowing of the heart’s main outflow valve; the link with ischemic stroke—a stroke caused by a blocked blood vessel—is weaker. For the valve, a Montreal Heart Institute team (first author Benoit Arsenault, senior author Jean-Claude Tardif) working with University of Cambridge colleagues followed about 17,500 people in England’s EPIC-Norfolk study for nearly 12 years. People in the top third for Lp(a) were more likely to develop aortic stenosis, and so were carriers of a gene variant that raises Lp(a). The authors wrote that this suggests the association “may be causal” (Circulation: Cardiovascular Genetics). (Note 1) Genetic evidence like this strengthens the case for causation. It doesn’t guarantee that every drug lowering the number will prevent events.
Why is one Lp(a) test usually enough?
The 2026 American College of Cardiology and American Heart Association dyslipidemia guideline, written with nine other societies, says Lp(a) “should be measured at least once in adulthood,” in the ACC’s summary. Because levels are “largely genetically determined and remain relatively stable over a lifetime,” the ACC adds, “repeat testing is generally not needed.” The NLA’s 2024 update makes the same once-for-every-adult recommendation. (Note 2)
The American Heart Association says about 1 in 5 people worldwide have high Lp(a) and that the standard lipid panel doesn’t include it. It says testing may be especially important for people with a personal or family history of premature heart disease, a family history of high Lp(a), or familial hypercholesterolemia (FH), an inherited condition that causes very high LDL from birth.
Because Lp(a) runs in families, the guideline recommends cascade testing—testing close relatives after a risk is found in the family—of first-degree relatives of people with FH, premature heart disease or high Lp(a); the AHA spells that out as parents, siblings and children. For children under 18, the NLA recommends selective testing only: those with suspected or confirmed FH, a first-degree relative with premature heart disease or high Lp(a), or an ischemic stroke with no known cause.
“Once” isn’t “never again.” The AHA notes that levels may rise with pregnancy and menopause, and with kidney, liver or thyroid disease. The NLA says people in its intermediate range may cross into the high range, especially women after menopause and people who develop kidney disease or an underactive thyroid, so a repeat test may make sense for them.
What an Lp(a) test gives you, and what it doesn’t
Testing can expose inherited risk a standard panel misses. It can also cause needless alarm if the number arrives without its unit, its limits or the rest of the cardiovascular picture. Here’s the trade in plain terms, drawn from the guideline and the NLA statement:
| What the result can add | What the result can’t answer |
|---|---|
| Flags a common, mostly inherited risk factor that the standard lipid panel leaves out | Doesn’t diagnose blocked arteries, a heart attack or aortic stenosis |
| Can explain part of a family pattern of early heart disease | Doesn’t prove that Lp(a) caused any one relative’s event |
| Can support earlier or more intensive management of the risks you can change | Doesn’t mean an Lp(a)-lowering drug has been shown to prevent heart attacks or strokes |
| Can prompt first-degree relatives to get tested | Doesn’t predict which relative will develop disease, or when |
Why read the unit before the Lp(a) number?
Here’s a detail lab reports don’t exactly shout about. Lp(a) comes back in one of two units: nanomoles per liter (nmol/L), which counts particles, or milligrams per deciliter (mg/dL), which weighs them. They aren’t two labels for the same ruler.
Because the extra protein varies so much in size, the same weight can mean different particle counts in different people. The NLA favors nmol/L and strongly advises against converting between the two with a fixed conversion factor. It also says a mg/dL result is much better than having no Lp(a) measurement at all. The 2026 guideline recommends labs whose tests aren’t thrown off by the protein’s size and are traceable to official reference standards. How the assays differ
If your result is 140, the unit changes the whole sentence. A value of 140 nmol/L sits just above the common US high-risk line. A value of 140 mg/dL is far higher. Keep the unit attached whenever you copy, compare or discuss the result.
What could be missed when Lp(a) results are compared without their units?
What counts as high Lp(a)?
The NLA sorts results into three bands. Under 75 nmol/L (30 mg/dL) counts as lower risk. From 75 to 124 nmol/L (30 to 49 mg/dL) is an intermediate “gray zone.” At 125 nmol/L (50 mg/dL) or above, it’s high. The NLA says the bands apply across races and ethnicities. See the bands and other countries’ cutoffs
These are separate guideline cutoffs for the two units, not a fixed conversion rule. The 2026 US guideline uses the same 125 nmol/L (50 mg/dL) line and ties it to about 1.4 times the long-term risk of heart attack or stroke compared with the population median of 20 nmol/L (7 mg/dL), per the ACC. At 250 nmol/L (100 mg/dL), long-term risk is at least doubled. At about 430 nmol/L (180 mg/dL), roughly the top 1% of people, European guidance describes risk similar to familial hypercholesterolemia. Other countries draw their lines in slightly different places, which is one more reason to keep the unit and ask which guideline is being applied.
These figures describe large groups, not any one person. Average levels differ by ancestry: the AHA says they tend to be higher in people of African descent and in South Asian populations. The same number can carry different weight depending on age, blood pressure, family history and everything else in a person’s cardiovascular picture.
A high result is a risk exposure, not a diagnosis. A 2025 review in Diabetes, Obesity and Metabolism, with first author Alexander Razavi of Emory University School of Medicine and co-authors at Johns Hopkins, UC San Diego, Wake Forest and Virginia Commonwealth University, reports that a family history of heart disease and high Lp(a) add to each other’s risk. In people who haven’t had a heart attack or stroke, it says, a coronary calcium score, which measures calcium deposits in heart arteries, can sharpen the picture: high Lp(a) with substantial calcium carried several times the risk, while high Lp(a) with no calcium added little once other risk factors were counted. The authors describe calcium scoring as a possible way to personalize risk assessment; they don’t present it as an automatic next test (full text). The review was commissioned for a journal issue funded by Roche Diagnostics, and several authors report ties to makers of Lp(a) drugs. (Note 3) The numbers
If lifestyle barely lowers Lp(a), what can you do?
“Although lifestyle changes don’t lower Lp(a) levels, you can lower your overall risk of heart disease and stroke,” says the American Heart Association, pointing to cholesterol, blood pressure, diabetes, physical activity and sleep. The 2026 guideline recommends early, optimal control of the cardiovascular risk factors that can be changed for everyone at 125 nmol/L (50 mg/dL) or above. Its broader lifestyle advice covers a healthy dietary pattern, regular activity, a healthy weight, sleep, stress management and avoiding tobacco.
Statins don’t lower Lp(a) and may nudge it up slightly, the NLA says. It adds that this shouldn’t be a reason to avoid or stop a statin, because statins clearly reduce ASCVD risk, meaning heart attacks and strokes caused by plaque.
PCSK9 antibody drugs (evolocumab and alirocumab) lower LDL cholesterol substantially and Lp(a) by about 20% to 30%, although they aren’t approved for Lp(a) itself, according to the NLA. The 2026 guideline does link them to Lp(a) in one group: people who already have heart disease and high Lp(a), and who haven’t reached their cholesterol goals on the highest statin dose they can tolerate. In a secondary analysis of the FOURIER trial of about 25,000 people with heart disease, evolocumab cut coronary events by about 23% in those with above-median Lp(a) and about 7% in those below it. The gap between the two groups fell just short of statistical significance. Each trial was funded by the maker of the drug it tested. (Note 4) The trial details
In the US, lipoprotein apheresis is the only FDA-approved therapy with a specific high-Lp(a) indication, per the NLA’s 2024 statement. It filters cholesterol-carrying particles from the blood, but it’s reserved for a narrow group with inherited high cholesterol, vascular disease and persistently high LDL and Lp(a). Levels drift back between sessions, and the treatment can be costly, time-consuming and hard to find. The eligibility details
Niacin and hormone therapy with estrogen and progesterone can lower the Lp(a) number. The NLA says trials adding niacin to statins showed no clinical benefit despite about 20% lower Lp(a), and it grades using niacin or hormone therapy to cut cardiovascular risk as a potential harm.
Did the first major Lp(a) outcomes trial meet its goal?
Several RNA-targeting drugs have cut Lp(a) dramatically in earlier trials. The open question has always been whether a lower number means fewer heart attacks, strokes and cardiovascular deaths.
On September 4, 2026, Novartis announced that pelacarsen, licensed from Ionis Pharmaceuticals, did not meet the primary goal of Lp(a)HORIZON. The phase 3 trial followed people with established cardiovascular disease and Lp(a) of at least 70 mg/dL while they received standard treatment. Pelacarsen lowered Lp(a), but the trial did not demonstrate a reduction in the combined rate of cardiovascular death, heart attack, stroke and urgent artery-opening procedures.
These are company topline results. Missing the prespecified goal means a benefit was not demonstrated; without the full estimates, it does not establish that the drug’s effect was exactly zero. As of September 25, 2026, the exact event numbers, subgroup results and full safety data haven’t been published. The result doesn’t erase the genetic evidence that high Lp(a) contributes to disease. It does show why moving a biomarker and improving a life are two different jobs.
In a statement on the topline results, the National Lipid Association said that “Lp(a) remains an important and independent risk factor for ASCVD. Clinicians and patients should continue to measure Lp(a).”
Other outcome trials from Amgen and Eli Lilly are still running; the earliest isn’t expected to finish before 2028, according to their registry entries. Until one reports, dramatic drops in the number are interesting pharmacology—not evidence that an Lp(a)-lowering drug prevents heart attacks. The trials still underway
What distinguishes evidence of a lower Lp(a) level from evidence of fewer cardiovascular events?
What’s Interesting
Lp(a) creates an unusual situation: the lifestyle measures the American Heart Association describes can lower overall cardiovascular risk while leaving the headline Lp(a) number almost untouched.
It’s also a clean lesson in how evidence stacks up. Genetic studies can show that a factor contributes to disease. Earlier trials can show that a drug moves the factor. Only an outcomes trial can show whether that drug prevents events. In September 2026, those three lines stopped pointing in the same tidy direction. Science doesn’t always resolve on schedule, or in the order everyone was hoping for.
What This Means in Practice
- Once-only testing: the 2026 US guideline recommends measuring Lp(a) at least once in every adult. It’s a blood test a clinician orders.
- Units matter: the NLA advises against fixed conversions; a result needs its unit to be interpreted.
- If it’s high, ask your clinician to place it in your overall cardiovascular picture: LDL cholesterol, ApoB or non-HDL cholesterol, blood pressure, blood sugar, kidney function, smoking and family history.
- Family testing: the guideline recommends testing first-degree relatives—parents, siblings and children—of people with FH, premature heart disease or high Lp(a).
- If you’re in the gray zone, ask whether a repeat test makes sense, especially around menopause or with kidney or thyroid disease.
- Specialist discussion: a preventive cardiologist or lipid specialist can explain inherited lipid disorders and how Lp(a) affects a treatment decision when results or guidance are unclear.
Nobody is an average. The risk figures come from large groups, and what they mean for you depends on your genes, your history and the rest of your health.
For another risk marker that is often ordered but easily overread, hs-CRP and Aging explains what an inflammation result can and cannot establish.
Bottom Line
Lp(a) is a common, mostly inherited risk factor for heart attack, stroke and aortic stenosis, and US guidance now says every adult should be tested once. A high number is not a diagnosis; the guideline recommends early control of other changeable cardiovascular risks in people with high Lp(a). Living longer isn’t something an Lp(a) test or a lower Lp(a) reading can promise: no study has shown either one extends lifespan, and the first large drug trial did not demonstrate a reduction in heart events. The next step is a conversation with your clinician about where the number fits.
A NOTE FROM LONGEVITY365
We read research, consult expert perspectives and work to make complicated health information easier to understand. What you’re reading here reflects how we’ve interpreted and organized that information. It is educational content—not personal medical advice, diagnosis or treatment guidance.
We’re not perfect, and neither is the available research. Evidence changes, new studies emerge and what’s appropriate for one person may not be appropriate for another.
Use this article as a starting point for your own research and conversations with qualified professionals. Always talk with your doctor or another trusted healthcare professional before making decisions that could affect your health, particularly if you take medications, are receiving treatment, have existing health conditions, are pregnant or have other circumstances that could affect what’s appropriate for you.
Reader Questions
A few questions to carry into the comments or your next conversation. Please leave out identifying or personal medical details.
- 01After reading this, what would you want a test result to actually help you decide?
- 02Which distinction changed how you read the evidence: "An LDL-like particle with an extra attachment" or "Did the first major Lp(a) outcomes trial meet its goal"?
- 03What would you ask a clinician, lab, or qualified professional before letting a number change a health decision?
Extra Insights & Sources
For readers who want the details behind each claim above.
What We Know
- Lp(a) is a mostly inherited ApoB-containing particle causally linked to atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Established from converging genetic and epidemiologic evidence.
- About one in five people worldwide has a high level. Supported (AHA; NLA; Novartis cites the same figure).
- Every adult should be tested at least once, according to current US and European guidance. Guideline recommendation.
- Risk rises continuously; 125 nmol/L (50 mg/dL) is a clinical decision line, not a biological switch. Established association; guideline threshold.
- Managing LDL cholesterol, blood pressure, diabetes, smoking and other modifiable factors lowers overall cardiovascular risk even when Lp(a) barely changes. Supported and guideline-endorsed.
What We Don’t Know
- Whether any Lp(a)-specific drug reduces cardiovascular events. Experimental. Pelacarsen’s phase 3 trial missed its primary endpoint; other agents haven’t reported outcomes.
- Why pelacarsen lowered Lp(a) but did not meet the primary goal for cardiovascular events. Unknown until full results are presented; explanations shouldn’t be promoted before then.
- Whether knowing or lowering Lp(a) extends lifespan. Unknown; no study has tested it.
- The ideal repeat-testing schedule for people in the intermediate range, and whether once-only testing holds in people who already have heart disease (the NLA says the latter still needs confirming). Not standardized.
- A universal safe value. Risk is continuous and interacts with the rest of the cardiovascular profile. Unsupported as a single cutoff.
The causal evidence in detail
HR (hazard ratio) compares event rates during follow-up: 1 means no difference, and 1.57 means an estimated 57% higher rate. CI means confidence interval, a range expressing statistical uncertainty. An odds ratio compares odds rather than probabilities: odds are the number with an outcome divided by the number without it. Neither ratio is an individual probability or a count of people helped.
European Atherosclerosis Society consensus (2022). The 22-author panel, led by Florian Kronenberg and published in the European Heart Journal, wrote that epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities, and that elevated Lp(a) is a risk factor even at very low levels of LDL cholesterol. It recommends testing Lp(a) at least once in adults, early intensive risk-factor management while specific therapies are lacking, and apheresis as an option for very high Lp(a) with progressive disease. It concluded that trials of specific Lp(a)-lowering treatments are critical to confirm any clinical benefit for cardiovascular disease and aortic valve stenosis. Its conflict-of-interest statement lists fees, grants or trial roles from many companies, including Novartis, Amgen, Ionis, Eli Lilly and Silence Therapeutics, for most authors. The public record doesn’t list a funding source for the statement.
Aortic stenosis study (2014). Benoit J. Arsenault and colleagues (senior author Jean-Claude Tardif, Montreal Heart Institute) measured Lp(a) in 17,553 EPIC-Norfolk participants; 118 developed aortic valve stenosis over a mean 11.7 years. The top Lp(a) third had higher risk than the bottom third (hazard ratio 1.57; 95% CI 1.02–2.42, adjusted for age, sex and smoking). Carriers of one or two copies of the rs10455872 G allele had hazard ratios of 1.78 (1.11–2.87) and 4.83 (1.77–13.20). A replication study of 379 patients and 404 controls found an odds ratio of 1.57 (1.10–2.26). The numbers of cases are small, so the confidence intervals are wide.
The testing recommendations in their own words
In these recommendations, ASCVD means cardiovascular disease caused by plaque in arteries; FH means familial hypercholesterolemia, the inherited high-LDL condition described above; and LDL-C and non-HDL-C are measures of cholesterol. Class 1 denotes a recommendation; B-NR and B-R distinguish nonrandomized from randomized evidence.
The 2026 guideline’s Lp(a) recommendations, as reproduced by Guideline Central and summarized here (Note 2): – Every adult should have Lp(a) measured at least once to help assess ASCVD risk. (Class 1, B-NR) – People with FH, premature ASCVD or high Lp(a) should have their first-degree relatives tested for high Lp(a), to find those at increased ASCVD risk. (Class 1, B-NR) – Labs should use assays that aren’t affected by apo(a) isoform size and that are traceable to official reference standard materials. (Class 1, B-NR) – Everyone with elevated Lp(a) (125 nmol/L or 50 mg/dL and above) should have early, optimal control of modifiable cardiovascular risk factors to reduce ASCVD risk. (Class 1, B-NR) – In people with clinical ASCVD and elevated Lp(a) not at LDL-C and non-HDL-C goals on maximally tolerated statin therapy, adding a PCSK9 monoclonal antibody that has cardiovascular outcome data is recommended. (Class 1, B-R)
The NLA’s 2024 update (Marlys Koschinsky, Western University, first author; Christie Ballantyne, Baylor College of Medicine, corresponding author) recommends selective testing in children under 18 with: clinically suspected or genetically confirmed FH; first-degree relatives with premature ASCVD (under 55 in men, under 65 in women); ischemic stroke of unknown cause; or first-degree relatives with elevated Lp(a). It says once-only measurement is reasonable for people in its low- or high-risk bands in primary prevention, but that this still needs confirming in people who already have ASCVD (secondary prevention). Nine of its 15 authors report consulting fees, research support or advisory roles with companies developing Lp(a) or PCSK9 drugs, including Novartis, Ionis, Amgen and Eli Lilly; the statement lists no funding source.
Thresholds by guideline
The NLA’s three bands:
| Lp(a) result | NLA interpretation | Caveat |
|---|---|---|
| <75 nmol/L or <30 mg/dL | Lower risk | Not zero cardiovascular risk |
| 75–124 nmol/L or 30–49 mg/dL | Intermediate “gray zone” | Repeat testing may be warranted |
| ≥125 nmol/L or ≥50 mg/dL | High risk | Overall risk still depends on the rest of the person |
The 2026 US guideline’s risk estimates, compared with a population median of 20 nmol/L (7 mg/dL): about 1.2-fold at 75–124 nmol/L, about 1.4-fold at 125 nmol/L (50 mg/dL, about the 80th percentile), at least 2-fold at 250 nmol/L (100 mg/dL, about the 95th percentile), about 3-fold at 350 nmol/L (150 mg/dL) and about 4-fold at 430 nmol/L (180 mg/dL, about the 99th percentile), which the guideline likens to the risk seen in heterozygous familial hypercholesterolemia. The 1.4-fold and 2-fold figures come from the ACC’s summary; the rest come from a reproduction of the guideline’s figure (Note 2).
International cutoffs don’t line up exactly. The 2025 ESC/EAS focused update says that in all adults, Lp(a) above 50 mg/dL (about 105 nmol/L) should be considered a factor that enhances cardiovascular risk (Class IIa, level B). The Razavi review’s table lists the European very-high level as 180 mg/dL or 430 nmol/L, Canada’s threshold as 50 mg/dL or 100 nmol/L, and Australia’s as 100 nmol/L.
How the assays differ
The NLA explains that apolipoprotein(a) carries a variable number of repeated kringle IV type 2 segments, from 3 to more than 40 copies. Antibodies that recognize that segment tend to underestimate smaller forms (which go with higher Lp(a) and higher risk) and overestimate larger ones. An immunochemical assay uses antibodies to recognize the protein being measured. Calibration means checking a test against reference material with an assigned value, so laboratory results can be compared. The WHO/IFCCLM material is an international reference for this purpose. Its summary recommendation is to use an immunochemical assay calibrated against the WHO/IFCCLM secondary reference material, with results reported in nmol/L (Class I). It recommends against converting mg/dL to nmol/L with a fixed factor (Class III, no benefit). It also advises against using a fixed factor to subtract Lp(a) cholesterol from calculated LDL cholesterol, because the cholesterol content of Lp(a) varies widely.
Family history and calcium scoring in detail
The Razavi review (first author Alexander C. Razavi, Emory; senior author Anurag Mehta, Virginia Commonwealth University) summarizes a 20-year study in which a family history of coronary heart disease was associated with 17% higher risk of atherosclerotic cardiovascular disease and elevated Lp(a) with 25%, while people with both had 43% higher risk. For people without prior heart attack or stroke, compared with people with neither high Lp(a) nor coronary calcium: Lp(a) of 50 mg/dL or more was associated with 29% higher risk; calcium scores of 1–99 and 100 or more with 68% and 2.7-fold higher risk; and both high Lp(a) and a calcium score of 100 or more with 4.7-fold higher risk. High Lp(a) with a calcium score of zero carried 31% higher risk, which was not significant after adjusting for traditional risk factors. The authors caution that these population studies skewed older and excluded people with prior events, so people with high Lp(a) and early disease may be underrepresented. The review also lists chronic kidney disease, liver disease, perimenopause and inflammation as sources of variability in Lp(a).
Treatments in detail
Statins. The NLA says statins don’t lower Lp(a) and may raise it slightly, and that worry about a rise in Lp(a) shouldn’t be a reason to discourage or stop statin treatment.
PCSK9 inhibitors. In the FOURIER Lp(a) analysis (Michelle L. O’Donoghue and colleagues, senior author Marc S. Sabatine; Circulation, 2019), Lp(a) was measured in 25,096 patients with established cardiovascular disease, median follow-up 2.2 years. Evolocumab reduced coronary heart disease death, heart attack or urgent revascularization by 23% (HR 0.77; 95% CI 0.67–0.88) with baseline Lp(a) above the median and 7% (HR 0.93; 0.80–1.08) at or below it (P interaction = 0.07). Absolute risk reductions over three years were 2.49% versus 0.95% (numbers needed to treat 40 versus 105). These are differences of 2.49 and 0.95 percentage points between the treatment and comparison groups in the two Lp(a) subgroups. The numbers needed to treat estimate how many comparable patients would receive treatment for three years to prevent one additional coronary event; they are not lifespan gains or individual guarantees. The authors said higher-Lp(a) patients “tended to derive greater coronary benefit.” FOURIER was funded by Amgen, which makes evolocumab. In a prespecified ODYSSEY OUTCOMES analysis (Vera A. Bittner and colleagues; Journal of the American College of Cardiology, 2020) of 18,924 patients after a recent acute coronary syndrome, alirocumab lowered Lp(a) by a median 5.0 mg/dL, and each 1-mg/dL reduction was associated with a hazard ratio for major events of 0.994 (95% CI 0.990–0.999), independent of LDL cholesterol. ODYSSEY was funded by Sanofi and Regeneron, which make alirocumab.
Apheresis. The NLA rates apheresis as reasonable (Class IIa) for high-risk patients with FH and coronary or peripheral artery disease whose Lp(a) remains ≥60 mg/dL (about 150 nmol/L) and LDL-C ≥100 mg/dL on maximally tolerated therapy, based on observational data. Because it removes all ApoB-containing particles, LDL and Lp(a) fall sharply after each session and then return toward pretreatment levels.
Niacin and hormone therapy. In a meta-analysis of 14 placebo-controlled trials of extended-release niacin (9,013 patients), niacin lowered Lp(a) by 23%. Later trials of statins plus niacin showed no clinical benefit despite about 20% lower Lp(a). The NLA recommends against using niacin, or hormone therapy with estrogen and progesterone, to reduce ASCVD risk, even though both lower Lp(a) concentration (Class III, harm).
Lp(a)HORIZON and the trials still running
RNA carries instructions used to make proteins. Antisense oligonucleotides, such as pelacarsen, and small interfering RNA (siRNA) drugs are short synthetic strands designed to interfere with those instructions and reduce production of apolipoprotein(a). This explains their intended way of lowering Lp(a), not whether they prevent disease. Muvalaplin is listed separately as an oral pill rather than an RNA-targeting injection.
Lp(a)HORIZON (NCT04023552) was a randomized, placebo-controlled, double-blind, multicenter phase 3 trial of pelacarsen, an antisense oligonucleotide, in 8,323 patients with elevated Lp(a) and established cardiovascular disease. The primary endpoint, a composite of cardiovascular death, non-fatal heart attack, non-fatal stroke and urgent coronary revascularization requiring hospitalization, was evaluated in the overall population (Lp(a) ≥70 mg/dL) and a subpopulation (Lp(a) ≥90 mg/dL). ClinicalTrials.gov lists the trial as completed on July 16, 2026. In Novartis’s September 4, 2026 release, Shreeram Aradhye, President, Development and Chief Medical Officer, said that although Lp(a) levels were lower with pelacarsen, the findings did not show that this translated into reduced cardiovascular risk in the overall study population. He added that the results were not what the company had hoped for, but that they provide important evidence about the relationship between lowering Lp(a) and cardiovascular outcomes and may help inform future approaches to cardiovascular risk management. The release gives no hazard ratio, confidence interval, subgroup result or adverse-event data. Novartis has a direct commercial interest in pelacarsen, which it licensed from Ionis Pharmaceuticals.
The NLA’s September 14, 2026 statement lists the other outcome trials underway. Status is as of September 25, 2026, from ClinicalTrials.gov:
| Trial | Drug (maker) | Who’s enrolled | Status |
|---|---|---|---|
| OCEAN(a)-Outcomes (NCT05581303) | Olpasiran, siRNA injection (Amgen) | 7,297 people with coronary artery disease and elevated Lp(a) | Active, not recruiting; estimated primary completion March 2028 |
| ACCLAIM-Lp(a) (NCT06292013) | Lepodisiran, siRNA injection (Eli Lilly) | About 17,300 planned, with ASCVD or at increased risk | Active, not recruiting; estimated primary completion March 2029 |
| OCEAN(a)-PreEvent (NCT07136012) | Olpasiran (Amgen) | About 11,000 planned, with high Lp(a) at high risk, before a first event | Recruiting; estimated primary completion October 2031 |
| MOVE-Lp(a) (NCT07157774) | Muvalaplin, oral pill (Eli Lilly) | About 10,450 planned, with a prior event or at high risk | Recruiting; estimated primary completion March 2031 |
Sources
- ACC/AHA and nine other societies (Blumenthal RS, Morris PB, Gaudino M, et al.). 2026 Guideline on the Management of Dyslipidemia, Circulation, 2026: DOI 10.1161/CIR.0000000000001423 (PDF; PubMed 41824552; corrections published June and September 2026)
- American College of Cardiology: ACC/AHA Issue Updated Guideline for Managing Lipids, Cholesterol (March 13, 2026)
- University of Illinois Chicago Drug Information Group: Key updates from the 2026 dyslipidemia guideline (May 2026)
- Guideline Central: ACC/AHA Management of Dyslipidemia Guideline Summary (page updated September 24, 2026)
- Novartis: 2026 ACC/AHA dyslipidemia guideline Lp(a) pocket guide for health care professionals (reproduces the guideline’s risk figure)
- Koschinsky ML, et al. A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice, Journal of Clinical Lipidology, 2024: NLA page; PDF; PubMed 38565461
- National Lipid Association: Top Line Results from the Phase 3 Lp(a)HORIZON Trial (September 14, 2026)
- American Heart Association: Lipoprotein(a)
- Kronenberg F, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement, European Heart Journal, 2022: PubMed 36036785
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- Razavi AC, et al. Why, how and in whom should we measure levels of lipoprotein(a), Diabetes, Obesity and Metabolism, 2025: PMC full text (PubMed 40437821)
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- O’Donoghue ML, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk, Circulation, 2019: PubMed 30586750
- Bittner VA, et al. Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome, Journal of the American College of Cardiology, 2020: PubMed 31948641
- Novartis: Lp(a)HORIZON phase III topline results (September 4, 2026)
- ClinicalTrials.gov: NCT04023552 (Lp(a)HORIZON); NCT05581303 (OCEAN(a)-Outcomes); NCT06292013 (ACCLAIM-Lp(a)); NCT07136012 (OCEAN(a)-PreEvent); NCT07157774 (MOVE-Lp(a))
Notes
Note 1: Funded by the Canadian Institutes of Health Research, the UK Medical Research Council and Cancer Research UK, according to PubMed’s grant record. The authors’ competing-interests statement isn’t publicly accessible.
Note 2: Guideline data in this article comes from published summaries, not the official report: the American College of Cardiology’s press release, Guideline Central’s reproduction of the recommendations and the University of Illinois Chicago Drug Information Group’s summary. The 1.2-, 3- and 4-fold risk estimates and percentiles come from a pocket guide published by Novartis, which makes pelacarsen, reproducing the guideline’s figure; the European 430 nmol/L level is also listed in the Razavi review. Circulation has published two corrections to the guideline (June 23 and September 8, 2026); as of September 25, 2026, we couldn’t read them to confirm whether either touches the Lp(a) recommendations.
Note 3: The review was commissioned for a themed issue on biomarkers funded by Roche Diagnostics; the journal says the sponsor’s identity wasn’t disclosed to the authors before publication. Alexander Razavi and Harpreet Bhatia report National Institutes of Health grants. Michael Shapiro, Harpreet Bhatia and Anurag Mehta report research support, consulting or advisory roles with companies including Novartis, Ionis, Amgen, Eli Lilly and Arrowhead.
Note 4: FOURIER was funded by Amgen, maker of evolocumab. ODYSSEY OUTCOMES was funded by Sanofi and Regeneron, makers of alirocumab.
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