Lp(a) -- drugs in clinical trials

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https://www.nytimes.com/2025/03/30/health/heart-attack-lpa-protein.html

Drug Reduces Mysterious Particle Involved in Heart Attack Risk

The Eli Lilly drug caused a major drop in the blood levels of Lp(a), but further research is needed to show that it will prevent heart attacks and strokes.

By Gina Kolata, The New York Times,
March 30, 2025

As many as one in five people — an estimated 64 million in the United States — have elevated levels of a tiny particle in their blood. It can greatly increase the risk of heart attacks and strokes.

But few know about it, and almost no doctors test for it, because there was not much to be done. Diet does not help. Neither does exercise. There have been no drugs…

On Sunday, cardiologists announced that an experimental drug made by Eli Lilly, lepodisiran, could lower levels of the particle, Lp(a), by 94 percent with a single injection. The effects lasted for six months and there were no significant side effects.

But it is not yet confirmed that reducing Lp(a) levels also reduces the risk of heart attacks and strokes. That awaits large clinical trials that are now underway…

Eli Lilly is now conducting a large clinical trial asking if its drug can prevent heart attacks or strokes or cardiovascular deaths. It will conclude in 2029. Clinical trials of other drugs targeting Lp(a) will conclude sooner. The first will be a study of a Novartis drug, injected monthly, with results expected in 2026.

Cardiologists caution, though, that there is no guarantee the drugs will protect people… [end quote]

A recent study showed that high Lp(a) coupled with high C-reactive protein (a marker of inflammation) dramatically increases cardiovascular disease.

Because of my heart problem I was approved for these tests (which are not part of regular screening). Fortunately my levels of both are low. My coronary arteries are clear.

Anyone with CVD in their family should have these tests.

If the clinical trial results are positive the drugs will be blockbusters for Eli Lilly and Novartis. It would be a matter of life and death since the level of Lp(a) is genetically controlled and can’t be changed by diet or exercise.
Wendy

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Well, over the past couple of years plus, we’ve had the opportunity to read about Lp(a) in detail thanks to the heads-up given by Peter Attia. Gina Kolata hasn’t done quite such a good job in educating her readership, which is a shame since there’s the potential for reaching a wider audience.

One of the first podcasts that gave me a heads-up on measuring this particle in the general population as a one off and at an early age (as is the case with any genetically derermined disorder) is this…

Not in itself a deep dive into Lp(a) pathophysiology like this one…

…but, in the course of discussing newer lipid lowering compounds (as well as the duds from the past) the effects of high levels as a risk multiplier were discussed and the need for aggressive control of other risk factors from an early age if disease prevention is the goal. Obviously, for me it was a post facto discovery of “why” rather than an exercise in primary prevention and would’ve been an excellent reason to pursue aggressive lipid lowering therapy if I’d needed any further persuading.

Of greater interest for me was has my daughter inherited this predisposition?? On her next physical, she did request advanced testing with Lp(a) and Apo-b lipoproteins added to the Usual Suspects. No problem in getting this as we both use the same primary care practice so our GP was totally on board, even though her LDL-C was in the healthy range. Low scores for both so no further need to measure Lp(a)

I am currently in a pool of potential recruits for a study on Lp(a) lowering medication…which might well not come to pass with the disruption in NIH funding.

Note to self: Repatha shot today!

Edit: I had it in my mind that some countries/cardiovascular organizations recommend the routine testing once for Lp(a) and set about seeing if I’d got it right. Found this straight away..

It’s hard to think of a rational argument not to test, really.

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As an example of passing knowledge on, my daughter has a new man in her life (where was he 15 years ago?) During some discussion on matters of the heart…the practical kind…he mentioned that he had “high cholesterol” and was on a statin. At age 42. In spite of reasonably healthy eating habits and exercise. Daughter sets the wheels in motion…first order of business, CAC scan. Not only a non zero score but into triple digits!!! At 42. Indicative of significant atherosclerotic deposition already. He too is now under the care of an intervention cardiologist and on more aggressive lipid lowering therapy than previously.

Another example of the demise of intellectual curiosity at primary care level. You’d think that, with non invasive tools at their disposal, the folk who don’t fit what seems to have become the accepted phenotype of someone at risk of ASCVD (fat, sedentary, smoker etc…) would warrant a bit of further interest and testing. I guess my experience isn’t that uncommon.

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For now.

This sort of statement is made at this stage a lot of the time. It is not true for many drug candidates once the drug is on the market. Drugs are later pulled from the market.

Conservative medicine do not take a drug that has not been in the market place for less than 5 years.

Anyone can test for LPA. The cost at Quest is $45. My score is 30. If you have a lower risk profile most insurance carriers won’t pay for the test. The issue is trying to determine when to medicate over the next 15 years. Giving the new drugs time to be pulled from the market if there are side effects.

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Well, that’s faulty reasoning. An easy mistake to make and reflective of the low risk tolerance and laissez-faire attitude that comes from not having much of a risk in the first place. 15 years is time enough for disease progression to be such that the cardiovascular events that primary prevention is supposed to avoid have occured.

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Excuse me but not everyone is your age.

Shooting down proper medical advice for the majority of people because of your predicament is not reasonable.

Where will you be when someone else prematurely takes one of these meds?

You do you if you can not figure things out for most people.

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Except the advice surrounding Lp(a) management isn’t advice for the majority, is it? Only about 1 in 5 of the population. Additionally, as a condition that has a strong genetic component, aggressive management is required early on in a person’s life since the disease process is probably underway in the neonate.

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You do not read or hear things with comprehension.

There is no management of this.

If a lot of people get tested 1 in 5 will show up with this. Assuming 4 reasonably low risk people also test.

The majority is from the 1 in 5 who need the development of a medication to treat. Those folks need to be wary of new meds.

This is not an easy topic for those who have the problem or condition. Your muddying the waters in every conversation helps no one.

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Yeah . . . .my LPa score is 205 - bummer. I found that out because I have a high CAC score. Bummer. I found that out because a 58 yr old friend of mine lived through the widowmaker heart attack. Pretty lucky. So I thought I would get a CAC score to see if I had a ticking time bomb in my heart - turns out I do.

So now my LDL level is 48, down from 87. Ezetimibe works very well for lowering LDL levels. Genetics is a b..ch.
My ApoliB is 76 - which is pretty good. HDL level is 64, which is also pretty good. Stress test was excellent. I’m 62 now, have always been in pretty good shape. Was overweight for a while - lost 20 lbs.

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How did you do that?

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Well I’m under the care of the Chief of Vascular Medicine and director of residency and fellowship programmes at Colorado Univ Health Sciences Center. These are the sort of places the studies get done.

One of my girlfriends back in England has already been recruited to a large multicenter European trial. Her LDL-C was even lower than mine, her Lp(a) only just outside of normal range…but she’s had a mild MI (that presented as shoulder pain and her GP ignored it) PLUS a mild stroke. These both happened in the Summer of 2021…shortly after we’d got together during a trip back to the UK and she, along with another of our cronies, were teasing me about all my testing (I’d had my CTangiogram just before the visit … the CAC, Lp(a) and Apo-b lipoproteins a couple of months earlier) and suggesting I was turning into an American with all these doctor’s visits. There you go!

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I should also add that, on a statin and PCSK9 inhibitor, my LDL-C is generally in the 30s now (from the 120s or so when my PCPs were calling it inconsequential). My HDL-C has from from the low 80s to low 70s and my triglycerides from about the same to the low 50s. My cardiologist has some patients with LDL-C down in the low 20s. Like I said upstream…aggressive lipid management is the order of the day for those of us with elevated Lp(a).

I don’t know whether your doctor explained the rationale of the super low level we’re at but, apparently, these numbers not only stop ASCVD from progressing, it’s possible to get actual reversal of the plaques. I would’ve been quite happy to stay where I am in spite of having the sort of functional flow measurement that used to suggest possible stenting…but I’ll take the reduction,TYVM!

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I honestly can not remember who somewhere perhaps not here argued that with me.

In many cases it stops potential plaque as well.

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I did see an article, sometime last year, about a med that clears out the plaques, but function was not recovered, in spite of the plaques being removed.

Steve

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Possibly something totally unrelated

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@steve203 “Clears out plaque” is not the medical language for what statins do to varying degrees at times differently on an individual basis.

A plumber can clear out a pipe but this is different. Cellular behavior would be altered in a more healing way.

Or you saw something different than a statin. I would not trust anything that reams away.

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Yes, different.

Steve