Can you lower Lp(a)? The drugs in trials, and why none is approved yet
For years the only honest advice on a high Lp(a) was to drive every other risk factor down, because nothing touched the number itself. Diet did not move it, exercise did not move it, and statins nudged it the wrong way. That is finally changing. Five drugs in trials lower Lp(a) by 80 to 95 percent, and the pace of lipid drug development just made the point for me: in July 2026 the FDA approved the first oral cholesterol pill of its kind. Lp(a) is the conspicuous gap in that progress, and closing it is close enough to plan around.
As of July 2026 no drug is approved to lower Lp(a), the mostly genetic particle that drives heart risk independent of your cholesterol. Five are in trials, cutting it 80 to 95 percent, but the first trial testing whether that lowering actually prevents heart attacks has not yet reported. Measure yours once now, before treatment arrives.
Why has Lp(a) had no treatment, when cholesterol has so many?
Because Lp(a) is not really a cholesterol problem, it is a genetics problem. Lipoprotein(a) is an LDL-like particle with an extra protein bolted on, and your level is set by the gene you inherited. It is roughly ninety percent heritable and stable across your adult life, which is exactly why the standard cholesterol toolkit does nothing useful to it. Statins lower LDL and can raise Lp(a) slightly. Diet and exercise, which move so much else, leave it flat.
Compare that to how fast the cholesterol side keeps advancing. On July 16, 2026, the FDA approved the first oral PCSK9 inhibitor, a once daily pill that cuts ApoB and LDL substantially. That is a real step, and it is worth naming precisely because it is not an Lp(a) drug. Oral PCSK9 inhibition lowers Lp(a) only modestly, on the order of 20 to 25 percent, and it is not indicated for it. So the same month that cholesterol got easier to treat, the Lp(a) gap stayed open. The drugs that close it are a different class built for this one job, and they are not approved yet.
What are the drugs that actually lower Lp(a)?
Five, at different stages, using three mechanisms. Four are injections that switch off Lp(a) production in the liver, either by degrading the messenger RNA for apo(a) (an antisense oligonucleotide) or by silencing it (a small interfering RNA). The fifth is an oral pill that blocks the particle from assembling in the first place.
| Drug | Type | How it is given | Lp(a) reduction (Phase 2) |
|---|---|---|---|
| Pelacarsen | Antisense oligonucleotide | Monthly injection | About 80 percent |
| Olpasiran | siRNA | Injection every 12 weeks | Over 95 percent |
| Lepodisiran | siRNA (long acting) | Infrequent injection | About 94 percent |
| Zerlasiran | siRNA | Injection | Around 80 to 90 percent |
| Muvalaplin | Oral small molecule | Daily pill | Up to about 85 percent |
The reductions are real and large, and they are also the reason to slow down rather than speed up. Every number in that column is a Phase 2 result, and every one of them measures Lp(a) itself, the marker. Not one of them is a result about heart attacks. That gap between lowering a number and preventing an event is the whole question, and it is not answered yet.
Does lowering Lp(a) actually prevent heart attacks?
We do not know yet, and anyone who tells you otherwise is ahead of the data.
The drug that will answer it first is pelacarsen, in a trial called Lp(a) HORIZON. It randomized roughly 8,300 people with established cardiovascular disease and a high Lp(a) to a monthly injection or placebo, and its primary endpoint is a composite of cardiovascular death, heart attack, and stroke. It is the first cardiovascular outcomes trial of any Lp(a)-lowering therapy, so its readout will define whether this entire approach works. That result was expected around the middle of 2026. As of this writing it has not been reported, so the field is genuinely still waiting for it. Amgen’s outcomes trial for olpasiran is running behind it, with completion estimated toward the end of 2026, and Lilly’s outcomes trial for lepodisiran is enrolling.
Why the caution matters: the history of lipid drugs is littered with markers that moved beautifully while patients did not benefit. Torcetrapib raised HDL and increased deaths. Niacin lowered several markers and failed to prevent events in the trials that mattered. The reason to expect Lp(a) lowering to be different is strong, and it is genetic. People who inherit naturally low Lp(a) have less heart disease across their whole lives, which is the kind of evidence that made Lp(a) a drug target in the first place. That is a good bet. It is not the same as a positive outcomes trial, and until HORIZON reads out, the honest statement is that we are testing a well founded hypothesis, not deploying a proven treatment.
What does the 2026 guideline tell you to do right now?
Measure it once. The 2026 ACC/AHA multisociety dyslipidemia guideline made measuring Lp(a) at least once in every adult a Class I recommendation, its strongest tier, and the first time universal Lp(a) screening has been recommended at that level. A single test captures your lifetime exposure, because the number does not drift.
The thresholds tell you what the result means. Risk climbs continuously, with roughly a 1.4 times increase in cardiovascular risk above 125 nmol/L and about double above 250 nmol/L. Ask for the result in nmol/L, the current particle based unit, rather than the older mg/dL mass units. If your number is high, you are in the roughly one in five adults who carry this, and the guideline’s logic is the same as it has always been: you cannot lower this one yet, so drive every other risk factor lower to compensate, ApoB first.
How should a self-experimenter play this?
The clinical floor here is do the one time test. The optimization case is do it now, specifically because the drugs are coming.
Here is the reasoning. Lp(a) is one of the highest value tests you will ever buy per krona: a single measurement, a few hundred SEK, never repeated. Right now the argument for it is knowing whether to push your other risk factors harder. Soon there will be a second argument. When an Lp(a)-lowering drug is approved, the first question any prescriber asks is what your Lp(a) is, and eligibility in the trials has centered on high baseline levels. The person who already has their number on file walks into that conversation ready. The person who deferred the test, which is precisely the mistake I keep making with my own, is starting from zero at the moment it finally matters. Getting the number now costs almost nothing and removes a future bottleneck.
Two honest cautions for this crowd specifically. First, do not let the pipeline talk you into chasing anything early. These drugs are investigational, and the outcomes data that would justify them does not exist yet. Lipoprotein apheresis, the one existing way to physically strip Lp(a) from blood, is reserved for extreme cases and is not a biohack. Second, be clear about what your current stack does not do. Nattokinase and omega-3 work on clotting and triglycerides, not on Lp(a). A statin lowers ApoB and does nothing good for Lp(a). None of what you may already be running touches this number, which is the entire reason a dedicated drug class had to be built, and the reason a high result changes what you do everywhere else rather than here. As always, these markers inform a decision you make with a clinician, not instead of one.
If you have never measured your Lp(a), order it on your next draw and record it as the one time value it is. When the first outcomes trial reports and the first drug is approved, you will already know whether the news is about you.
FAQ
Can you lower Lp(a) with medication?
Not with an approved drug yet, as of July 2026. Five drugs that lower Lp(a) by 80 to 95 percent are in clinical trials, using antisense, siRNA, or an oral small molecule. None is FDA approved, because approval is expected to depend on cardiovascular outcomes data, and the first such trial has not reported whether lowering Lp(a) prevents heart attacks.
Can you lower Lp(a) naturally with diet or exercise?
No. Lp(a) is roughly ninety percent genetic and stable across adult life. Diet, exercise, and weight loss do not meaningfully move it, and statins can raise it slightly. This is why a single measurement captures your lifetime exposure, and why a high result is managed by lowering every other risk factor rather than by targeting Lp(a) itself.
What Lp(a)-lowering drugs are in trials?
Pelacarsen (antisense), olpasiran, lepodisiran, and zerlasiran (all siRNA injections), and muvalaplin (an oral pill). In Phase 2, injectable agents lowered Lp(a) by roughly 80 to over 95 percent, and the oral agent by up to about 85 percent. These are reductions in the marker, not proven reductions in heart attacks.
When will an Lp(a) drug be approved?
Unknown, and it depends on the outcomes trials. Pelacarsen’s Lp(a) HORIZON trial, the first to test whether lowering Lp(a) prevents cardiovascular events, was expected to report around mid 2026 and had not been reported as of late July 2026. Approval would follow a positive outcomes result, so timing hinges on those readouts, not on the lowering data alone.
Does lowering Lp(a) actually reduce heart attack risk?
Not proven yet. The case is strong because people born with low Lp(a) have less heart disease, but genetic evidence is not the same as a positive trial. Lipid history includes drugs that improved markers without helping patients. The Lp(a) HORIZON outcomes trial is designed to answer this, and until it reports the question is formally open.
Is any Lp(a) drug the same as the new oral cholesterol pill?
No. The oral PCSK9 inhibitor the FDA approved in July 2026 lowers LDL and ApoB and is a cholesterol drug, not an Lp(a) drug. It lowers Lp(a) only modestly, around 20 to 25 percent, and is not indicated for it. The dedicated Lp(a)-lowering drugs are a separate class and remain investigational.
Should I get my Lp(a) tested now if drugs are not approved yet?
Yes. The 2026 guideline recommends measuring it once in every adult. Knowing your number now tells you how hard to push your other risk factors, and it means that when an Lp(a) drug is approved you already have the baseline a prescriber will ask for. It is a one time test that never needs repeating.
Sources
- 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia, Circulation: Lp(a) measured once in all adults as a Class I recommendation, and the risk multipliers above 125 and 250 nmol/L
- FDA approves first oral PCSK9 inhibitor, July 16 2026: the oral cholesterol drug that lowers LDL and ApoB but is not an Lp(a) therapy
- Lp(a) HORIZON outcomes trial (pelacarsen), ClinicalTrials.gov NCT04023552: the first cardiovascular outcomes trial of an Lp(a)-lowering drug, primary endpoint and design
- Small Interfering RNA to Reduce Lipoprotein(a) (olpasiran, OCEAN(a)-DOSE), NEJM 2022: the Phase 2 reduction of over 95 percent, a surrogate marker result
- Lepodisiran for Lipoprotein(a) (ALPACA), NEJM 2025: the Phase 2 reduction of about 94 percent from a long acting siRNA
- Oral Muvalaplin for Lowering of Lipoprotein(a) (KRAKEN), ACC 2024: the oral agent’s Phase 2 reduction of up to about 85 percent
- Lipoprotein(a) Reduction in Persons with Cardiovascular Disease (pelacarsen Phase 2), NEJM 2020: the antisense agent’s dose dependent reduction of about 80 percent