Until recently, hardly at all. Statins do not lower Lp(a), and PCSK9 inhibitors lower it only modestly. A new class of injectable drugs, including pelacarsen and olpasiran, can lower Lp(a) by roughly 80 to 95% by quieting the gene that makes it. They are still experimental and not yet approved, and the trials testing whether this prevents heart attacks are ongoing.

What are pelacarsen and olpasiran?

They are two of the new drugs designed to lower lipoprotein(a). Pelacarsen is an antisense oligonucleotide and olpasiran is a small interfering RNA, but both work by telling the liver to make far less of the Lp(a) particle. In trials they lowered Lp(a) by about 80% and 95%. Neither is FDA-approved yet; both are in large trials to see whether lowering Lp(a) reduces cardiovascular events.

Are the new Lp(a) drugs available?

Not by prescription yet. As of 2026, none is FDA-approved, so the main way to access one is through a clinical trial. The first major outcome trial, testing pelacarsen, is expected to report around 2026, and approval, if the results are positive, would follow after that.

Do the Lp(a) drugs lower cholesterol too?

Not meaningfully. These drugs are specific to lipoprotein(a) and do not lower LDL cholesterol much, so they are not a replacement for a statin. Someone with both high Lp(a) and high LDL would still need standard cholesterol treatment alongside any Lp(a)-specific drug. They target one specific risk rather than the whole lipid picture.

Is high Lp(a) dangerous if I feel fine?

High Lp(a) causes no symptoms, which is why it is important to measure it. It raises the lifetime risk of heart attack, stroke, and aortic valve narrowing, often in people who look and feel healthy. Knowing your number lets you and your physician lower your other risks to compensate, which is the most effective step available today.

Until recently, hardly at all. Statins do not lower Lp(a), and PCSK9 inhibitors lower it only modestly. A new class of injectable drugs, including pelacarsen and olpasiran, can lower Lp(a) by roughly 80 to 95% by quieting the gene that makes it. They are still experimental and not yet approved, and the trials testing whether this prevents heart attacks are ongoing.

What are pelacarsen and olpasiran?

They are two of the new drugs designed to lower lipoprotein(a). Pelacarsen is an antisense oligonucleotide and olpasiran is a small interfering RNA, but both work by telling the liver to make far less of the Lp(a) particle. In trials they lowered Lp(a) by about 80% and 95%. Neither is FDA-approved yet; both are in large trials to see whether lowering Lp(a) reduces cardiovascular events.

Are the new Lp(a) drugs available?

Not by prescription yet. As of 2026, none is FDA-approved, so the main way to access one is through a clinical trial. The first major outcome trial, testing pelacarsen, is expected to report around 2026, and approval, if the results are positive, would follow after that.

Do the Lp(a) drugs lower cholesterol too?

Not meaningfully. These drugs are specific to lipoprotein(a) and do not lower LDL cholesterol much, so they are not a replacement for a statin. Someone with both high Lp(a) and high LDL would still need standard cholesterol treatment alongside any Lp(a)-specific drug. They target one specific risk rather than the whole lipid picture.

Is high Lp(a) dangerous if I feel fine?

High Lp(a) causes no symptoms, which is why it is important to measure it. It raises the lifetime risk of heart attack, stroke, and aortic valve narrowing, often in people who look and feel healthy. Knowing your number lets you and your physician lower your other risks to compensate, which is the most effective step available today.

Can You Lower Lp(a)? The New Lipoprotein(a) Drugs | Philadelphia

TL;DR30-second take

Lipoprotein(a), or Lp(a), is a mostly genetic cholesterol particle that raises the risk of heart attack, stroke, and aortic valve disease, and until recently there was no drug that lowered it much. That is changing. A new class of injectable drugs, including pelacarsen and olpasiran, quiets the gene that makes Lp(a) and can lower it by roughly 80 to 95%. The catch is that they are still experimental: none is FDA-approved yet, and the trials testing whether lowering Lp(a) prevents heart attacks are still running, with the first results expected around 2026. So the current state is that we can now lower Lp(a) dramatically, but we do not yet know if that translates into fewer events.

TL;DR: Lipoprotein(a), or Lp(a), is a mostly inherited cholesterol particle that raises the risk of heart attack, stroke, and aortic valve disease, and for decades there was no way to lower it that mattered. A new class of injectable drugs, led by pelacarsen and olpasiran, silences the gene that makes Lp(a) and lowers it by roughly 80 to 95%. That is a dramatic, unprecedented drop. The honest catch is that lowering Lp(a) is proven while preventing heart attacks by lowering it is not: none of these drugs is FDA-approved, and the outcome trials are still running, with the first (HORIZON) expected around 2026. If your Lp(a) is high, the best move today is to lower every other risk factor hard and to know your number while these drugs mature.

Why has Lp(a) been so hard to treat?

Lipoprotein(a), usually shortened to Lp(a), is an LDL-like cholesterol particle wrapped in an extra protein called apolipoprotein(a). Your level is about 80 to 90% set by your genes, fixed close to birth, and it raises the risk of heart attack, stroke, and narrowing of the aortic valve. Roughly one in five people carries a high level, and most have never had it measured.

The frustrating part, for decades, was that we could measure Lp(a) but not lower it in a way that mattered. Statins do not lower Lp(a), and can nudge it up slightly. PCSK9 inhibitors drop it modestly, by about 20 to 25%, as a side benefit. Niacin lowers it but was abandoned after trials showed no heart benefit and meaningful harms. The only established way to pull Lp(a) down substantially has been apheresis, a dialysis-like procedure that filters it from the blood, which is invasive and reserved for extreme cases. So a person with high Lp(a) was usually told to lower everything else and manage the risk around it. That is what is now changing.

How do the new Lp(a) drugs work?

The new drugs go after Lp(a) at its source: the gene. Your liver reads the LPA gene to build apolipoprotein(a), the protein that defines Lp(a). These drugs are short strands of genetic material that intercept that instruction before the protein is made, so the liver produces far less of it. Two designs are in play. Pelacarsen is an antisense oligonucleotide, and the others, including olpasiran, lepodisiran, and zerlasiran, are small interfering RNA drugs. Both approaches silence the same gene, just by slightly different means.

Because they work upstream, at the level of production, they lower Lp(a) far more than anything that acts on the finished particle. And because a single dose keeps the gene quiet for weeks to months, they are given as an injection under the skin, ranging from monthly for pelacarsen to once every few months for the siRNA drugs.

How much do they lower Lp(a)?

A lot, which is what sets them apart from the past. In their trials, pelacarsen lowered Lp(a) by about 80%.¹ The siRNA drugs went further: olpasiran lowered it by roughly 95%,² and lepodisiran and zerlasiran reached similar heights.³ ⁴ These are reductions unlike anything medicine could offer for Lp(a) before.

One number needs a caveat. You may see figures above 100% for olpasiran; that is a quirk of how the reduction is calculated against a placebo group whose Lp(a) drifted up, rather than a claim that levels went below zero. The plain reading is that these drugs cut Lp(a) by most of the way, often to very low levels.

Do they prevent heart attacks and strokes?

This is the question that matters, and the straight answer is that we do not know yet. Lowering Lp(a) is now proven. Whether lowering it prevents heart attacks and strokes is being tested, and no such trial has reported results.

The first answer is close. Lp(a) HORIZON, a trial of pelacarsen in more than 8,000 people with heart disease, is expected to report around 2026, and it will be the first look at whether lowering Lp(a) changes outcomes.¹ A second large trial of olpasiran is due soon after.² Until those results arrive, the case for these drugs rests on strong logic: people born with genetically low Lp(a) have less heart disease, so lowering it should help. But logic is not proof, and cardiology has been humbled before by drugs that improved a number without helping patients. That is why these trials exist, and why no careful clinician should promise the benefit before they read out.

It is also why none of these drugs is approved yet. They are investigational, available for now mainly through clinical trials.

What should you do about high Lp(a) now?

If your Lp(a) is high, the plan today is the same one we have used all along, and it is more useful than it sounds. Because Lp(a) adds to your overall risk, the move is to lower everything else you can control, hard. That means driving your ApoB and LDL down to aggressive targets with a statin and, if needed, ezetimibe or a PCSK9 inhibitor, keeping blood pressure tight, not smoking, and staying fit. A PCSK9 inhibitor has the bonus of trimming Lp(a) by a fraction as well.

The second move is to know where you stand. Measuring Lp(a) once in your life tells you if you carry this risk, and if you do, imaging like a coronary calcium score can show whether it has begun to affect your arteries, which sharpens how aggressive to be. And then there is the part that is new: for someone with very high Lp(a) and established disease, a clinical trial of one of these drugs may be an option to discuss. When the outcome results land, this conversation will change quickly.

Guidance from the Clinic

"High Lp(a) used to be the conversation I dreaded, because I would tell a patient they carried a serious inherited risk and then, in the same breath, admit I could not lower it directly. That era is ending, and it is one of the developments I am most excited about in preventive cardiology. What I am careful about is the gap between lowering the number and proving it saves lives, because that proof is still coming. So for now I do two things: I lower every other risk factor aggressively, which does help, and I keep a close eye on the HORIZON trial. For the right patient, someone with sky-high Lp(a) and established disease, I will talk through whether a trial makes sense. When these drugs prove themselves, and I suspect at least one will, high Lp(a) will have a treatment of its own. Your job in the meantime is to know your number."

Key Takeaways

Lipoprotein(a), or Lp(a), is a mostly genetic cholesterol particle that raises the risk of heart attack, stroke, and aortic valve disease, and it has long had no specific treatment.
A new class of injectable drugs, including pelacarsen and olpasiran, silences the gene that makes Lp(a) and lowers it by roughly 80 to 95%.
Lowering Lp(a) is now proven, but whether that prevents heart attacks and strokes is still being tested, with the first trial (HORIZON) expected to report around 2026.
None of these drugs is FDA-approved yet; they are investigational, available mainly through clinical trials.
If your Lp(a) is high, the best step today is to lower every other risk factor aggressively and to know your number, while the outcome trials mature.

Lp(a): The Genetic Risk Most Panels Miss - what Lp(a) is and why it matters
ApoB and Heart Health - the cholesterol target to drive down alongside Lp(a)
Beyond Statins: Other Ways to Lower Cholesterol and ApoB - the tools for the rest of your risk
Coronary Calcium Score - checking whether Lp(a) has affected your arteries
What Is a Preventive Cardiologist? - the decision layer around high Lp(a)

Scientific References

Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, et al. "Lipoprotein(a) Reduction in Persons with Cardiovascular Disease." New England Journal of Medicine. 2020;382(3):244-255.
O'Donoghue ML, et al. "Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease." New England Journal of Medicine. 2022;387(20):1855-1864.
Nissen SE, et al. "Lepodisiran - A Long-Duration Small Interfering RNA Targeting Lipoprotein(a)." New England Journal of Medicine. 2025;392(17):1673-1683.
Nissen SE, Wang Q, Nicholls SJ, et al. "Zerlasiran - A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial." JAMA. 2024;332(23):1992-2002.

Fishtown Medicine | Cardiovascular risk

2418 E York St, Philadelphia, PA 19125(267) 360-7927 hello@fishtownmedicine.comHSA/FSA Eligible

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Frequently Asked Questions

Common Questions

Deep-Dive Questions

Statins work by increasing the liver's uptake of LDL cholesterol, but Lp(a) is made and cleared through partly different machinery, so that mechanism does not touch it. In fact, statins can raise Lp(a) by a small amount. This does not make statins a mistake in someone with high Lp(a); they still lower ApoB and overall plaque, which reduces risk. It simply means a statin alone leaves the Lp(a) part of the risk untouched, which is the gap the new drugs aim to fill.

The difference is where they act. Older drugs worked on the finished Lp(a) particle or on related pathways, which could barely move it. The new drugs act on the gene, intercepting the instruction the liver uses to build apolipoprotein(a) before the particle is ever made. By cutting production at the source, they lower Lp(a) far more than older approaches could. It is the same gene-silencing strategy behind other modern drugs, aimed here at the one protein that defines Lp(a).

Lp(a) HORIZON is testing whether lowering Lp(a) with pelacarsen reduces cardiovascular events in people with heart disease and high Lp(a). It is the first trial to answer the central question: does lowering Lp(a) prevent heart attacks and strokes, or does it only improve a lab value? A positive result would establish Lp(a) as a treatable cause of heart disease and likely lead to approval. A neutral result would be a major disappointment and would reshape how we think about the risk. Either way, expected around 2026, it is one of the most consequential trials in cardiology.

Yes, at least once. Every adult should know their Lp(a) at least one time, because it is a common, inherited, and independent risk factor that standard cholesterol panels leave out. If it is high, it changes how aggressively you and your physician manage everything else, and it may make you a candidate for one of the new drugs or their trials down the line. Since the level is mostly stable through life, a single measurement usually tells you what you need to know.

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