High Lipoprotein(a): Actionable Strategies for Risk Assessment and Mitigation 2024
Novel therapies that target apo(a) are at different clinical trial stages and substantially lower Lp(a) levels in patients with high Lp(a). This is critically important in the context of Lp(a) level population distribution, which is generally skewed, and has more than a 1000-fold range of concentrations between individuals. Therefore, those with the highest levels of Lp(a) will likely require large, absolute reductions in Lp(a) levels to effectively manage their CVD risk.
Two are in Phase 3: pelacarsen & olpasiran. We can expect approval in 2026 at best. Most likely 2027–2028.
They also mention obicetrapib which divides Lip(a) by 2 (see also the dedicated topic: Obicetrapib (CETP inhibitor for dyslipidemia) - #48 by adssx ).
And then the challenge will be coverage/availability. Those of us with high Lp(a) but no history of actual cardiac events may not qualify for coverage for primary prevention. Hopefully it will be available from India 
Chris, can you give a one sentence intro or summary about the video - there are so many videos posted that most of us have to choose which ones to engage
And unlike links to papers or blogs, etc, one cannot “skim” a video to determine if one should invest in it or to just take away the high level.
Think it would be a great best practice for how we all can help each other in the most efficient and impactful ways.
FWIW: This is a short video.
It’s about 20 seconds long. For shorts, the summary is the title.
However, I could say short video at the top and you can read the title of the video.
You wrote: “I take 2.125g of immediate release metformin”
You take two, 125 grams immediate release metformin–that’s a mighty big tablet, I would think since each would contain 125,000mgs Metformin… ??
Pioglitazone seems scary… But then diabetes is scary too…
No, I don’t take it all in one go, and I have cut back on the total dose of metformin I now take. As it’s immediate release, I take it (1/2 of 750mg tablet) an hour before meals, and just before bedtime.
I’m going to order some extended release metformin and do a head-to-head study whilst wearing a CGM.
Yes, Pioglitazone is a bit ‘scary’, with its risk of bone fractures etc, I used to work (in drugs research) with its cousin Rosiglitazone. I take a micro dose 1/4 of a 30mg tablet, so 7.5mg dose, which has been shown to be efficacious
I take the pioglitazone along side a 1g omega 3 soft gel to boost the efficacy
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30237-0
Interesting info! How long have you taken the pioglitazone and did you notice any changes in blood parameters?
I’ve taking it for about a year now, I’ve only started taking measurements recents HbA1c etc so can really say.
Now I’ve got my blood pressure meds sorted, I’m planning on stopping my glucose meds (to get a baseline) and re introducing them slowly to see what works for me and what doesn’t.
Thanks for the feedback, keep us updated!
This is a link to register for clinical trial for Lp(a) - lowering med (I’m not sure which one)
I registered and got a text saying they’ll let me know if/when a trial is taking place in my area 
In fact, not in any way related to the topic of new Lp(a) lowering drugs or Lp(a). Why post it here? You could create a new thread instead of derailing the subject of this one.
Not quite true what you are saying. I thought level of Lp(a) is in fact somehow related to what people eat, no? I guess you could swipe left if you don’t like something you read! Plus, sharing what works and what doesn’t for certain health condition should be considered kosher for these boards, no?
No. Diet has minimal impact on Lp(a), unlike LDL/ApoB.
One of / the top Lp(a) doc in the world is answering questions via twitter tomorrow
https://twitter.com/lpa_doc/status/1781362823689535524?s=46&t=zJMJ1xVdRJYEDYz-DHipTw
https://x.com/Lpa_Doc/status/1781723202785583371
Edit: here’s the link to the actual paper from the photo in the tweet. I think the “may even increase Lp(a)” comment is specific for statins, not “any 3rd med”.
So my interpretation is that if you’re just looking at LDL-C, it can be confusing in those with high Lp(a) because some of that cholesterol is actually carried on Lp(a) not LDL. Which is all the more reason for looking at the actual particle numbers of LDL and Lp(a) instead of a secondary surrogate like cholesterol, or at the very least ApoB instead of LDL-C, since it’s a better surrogate for atherogenic particle number.
Published: 08 May 2024
Discovery of potent small-molecule inhibitors of lipoprotein(a) formation
Pelacarsen, an antisense oligonucleotide that targets LPA , and olpasiran, an LPA small interfering RNA, are both injectable therapeutics that are currently in phase 3 clinical studies. These interventions have shown a robust Lp(a)-lowering effect, with good tolerability16,17. Results from ongoing phase 3 cardiovascular outcome trials, such as HORIZON and OCEAN(a), will provide much-needed evidence about the therapeutic utility of Lp(a)-lowering treatments18,19.
So far, no small molecule that specifically targets apo(a) has been studied in humans; however, the plasminogen inhibitor tranexamic acid was found to reduce the levels of Lp(a) in a small clinical study20. The goal of our research was to develop a potent and selective orally delivered small-molecule therapeutic to inhibit the formation of Lp(a) by blocking the first interaction between apo(a) and apoB to reduce the circulating levels of Lp(a). A potent and selective small-molecule Lp(a)-reducing therapeutic could provide a way to decrease the number of primary and/or secondary major adverse cardiovascular events in patients who are at risk of cardiovascular disease because of their high levels of Lp(a).
Open access:
https://www.nature.com/articles/s41586-024-07387-z
Published: 09 May 2024