Podcast episode 89 (in German)
Lipoprotein(a) – the trial that failed on September 4
September 27, 2026
On September 4, the trial that was meant to show that lowering lipoprotein(a) can prevent heart attacks failed. The value itself nevertheless remains one of the most cleanly established risk factors in cardiology.
What it is about
Lipoprotein(a) is an LDL particle with an attachment: the long, twisted apolipoprotein(a), which makes it stickier and apparently more pro-inflammatory. The level is genetically determined, fixed at birth and practically cannot be shifted by diet, exercise or statins. About one in five people has an elevated level without knowing it, because it is not measured in the standard cholesterol check. Pelacarsen was meant to change that, preventing the attachment from being built in the liver in the first place. In the Lipoprotein(a)-HORIZON trial with 8,323 patients, the level did fall markedly — but the number of cardiovascular events did not. The episode goes through three explanations and sorts out what this means for your own prevention.
Key points
- The lipoprotein(a) level is genetically determined and barely changes over a lifetime; a single measurement in your life is enough, and it is not included in the standard cholesterol check.
- About one in five people has an elevated level, and most do not know it, because the test has to be requested separately.
- Mendelian randomization shows very clearly that genetically high lipoprotein(a) leads more often to heart attack — as close to causality as you can get without a drug.
- In Lipoprotein(a)-HORIZON, 8,323 patients with established cardiovascular disease and levels of 70 mg/dl or more received pelacarsen; a group with 90 mg/dl or more had been prespecified.
- In earlier studies the level fell by up to 80 percent, yet the primary endpoint of cardiovascular death, heart attack, stroke and urgent procedures was missed on September 4.
- As early as 2018, Burgess and Ference calculated that an absolute reduction of just over 101 mg/dl would be needed to match the risk reduction of lowering LDL by just under 39 mg/dl.
- Three further drugs are in large trials: olpasiran with results around 2028, lepodisiran around 2029 and muvalaplin, which is given as a tablet.
Where the data stop
What is established is that lipoprotein(a) contributes to causing the damage. What is not established is that lowering it later reverses that damage — two different statements that are regularly lumped together. There is currently no drug that has been proven to prevent heart attacks by lowering lipoprotein(a). None.
Why HORIZON failed is an open question. It is conceivable that the baseline level of those included, from 70 mg/dl upward, was too low to achieve enough absolute reduction in the first place: with an 80 percent reduction, you end up at 60 mg/dl there. It is also conceivable that the participants, who were already comprehensively treated, left little room, or that decades of high levels leave vascular changes that 5 years of medication can no longer reverse. The full data will only be presented at a scientific congress. Getting your level measured remains worthwhile, especially if there are early heart attacks in the family.
Listen (in German)
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Published on September 27, 2026.
The topic in the database
- An LDL-like particle with an additionally attached apolipoprotein(a), whose level is genetically determined and barely changes over a lifetime. …Lipoprotein(a)
Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-09-19.