adssx
#189
From what I understand the paper doesn’t claim Lp(a) lowering but lowering its oxidation so potentially making it less “harmful”. Could it explain the MACE reduction in REDUCE IT (pure EPA)?
2 Likes
Davin8r
#190
Have we talked about this paper before? It’s a meta analysis of CoQ10 and Lp(a) lowering. At first, the degree of lowering seem trivial, but in the fine print:
[CoQ10 supplementation led to a]…“numerically greater reduction in plasma Lp(a) concentrations in the subset of trials with baseline Lp(a) values ≥ 30 mg/dL (WMD: -11.72 mg/dL, 95% CI: -21.01, -2.42,
p=0.013) compared with the subset with baseline values < 30 mg/dL (WMD: -3.14 mg/dL, 95% CI:
-4.92, -1.35, p=0.001”
Also: “Subgroup analysis suggested that the impact of CoQ10 on plasma Lp(a) was greater at supplemental doses < 150 mg/day (WMD: -9.24 mg/dL, 95% CI: -15.19, -3.29, p = 0.002) compared with doses ≥ 150 mg/day (WMD: -2.75 mg/dL”
So I wonder what the average reduction would be in someone using both a low dose of CoQ10 and who had a higher baseline Lp(a)?
That 11.72 reduction is significantly higher when converted to modern units (nmol/L), this is roughly 12 x 2.5 = 30 nmol/l, right? Not huge, but definitely significant.
Add a daily baby aspirin to that to knock it down a little more (along with platelet inhibition).
CoQ_Lpa_Review.pdf (1.1 MB)
2 Likes
adssx
#191
It would be good to have more recent papers on the topic, but note CoQ10 also has a U-curve for glucose and blood pressure with an optimum around 100 mg/day: Coenzyme Q10 (CoQ10) U-shaped dose-response relation with blood glucose and blood pressure
Bryan Johnson takes 50 mg/day of ubiquinol (reduced Q10).
4 Likes
59vw
#192
Actually it looks like the optimum is closer to 200 mg/day (perhaps splitting hairs here)
Davin8r
#193
Not for reducing Lp(a) – less than 150mg/day
Neo
#194
In what context, can you share the source please, would be helpful to be able to triangulate
59vw
#195
in the link that @adssx posted above (post 182 of this thread). I only commented because I take 200 mg and that is what I’ve found to relieve statin induced muscle soreness most effectively.
Thorin
#196
3 Likes
That looks like a great new drug!
Thorin
#198
I think it is an oral, per the article:
" Lilly’s drug is the only oral treatment in a field of several injectable therapies being tested to treat high Lp(a), a risk factor for heart disease that affects one in five individuals globally.
Unlike low-density lipoprotein, or LDL, the so-called bad cholesterol that can be treated with diet and statins, there are no approved treatments for Lp(a) and few individuals even know they have it."
3 Likes
Thorin
#199
It does seem interesting. "At week 12, the study found:
- Compared to placebo, muvalaplin treatment reduced Lp(a) by up to 70% as measured by the traditional blood test […]"
That is a large reduction!
I am not sure that anyone has actually shown that reducing Lp(a) actually improves health outcomes though. I - and everyone else, I guess - suspect it does, which is the reason for the interest. Anyway, quoting a different article:
“We were encouraged by the degree of Lp(a)-lowering in these patients who are most likely to benefit from its use and by the safety and tolerability,” Nicholls said. “While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes.”
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https://www.reuters.com/business/healthcare-pharmaceuticals/lilly-pill-cuts-genetic-form-cholesterol-nearly-86-study-2024-11-18/
Quote:
“ The drug, muvalaplin, reduced levels of lipoprotein(a), or Lp(a), by 70% using a traditional blood test and by nearly 86% based on a more specific test developed by the company, researchers reported at the American Heart Association meeting in Chicago.”
3 Likes
Recent JAMA article published 18 Nov '24: Zerlasiran–A Small-Interfering RNA Targeting Lipoprotein(a). A Phase 2 Randomized Clinical Trial
Conclusion: Zerlasiran was well-tolerated and reduced time-averaged lipoprotein(a) concentration by more than 80% during 36 weeks of treatment in patients with ASCVD
Little to none adverse effects.
My question to this readership: does anyone know the average length of time from Phase 2 to being available to the public? Thanks
Thank you. I was hoping for a somewhat shorter timeline as would love to have these new drugs available for my high Lp(a).
2 Likes
drfawn
#205
Unless it is a Covid vaccine!!
Neo
#206
Compared to that one that was in Phase 2, these might be approved faster:
-
Olpasiran is currently in a phase 3 clinical trial named OCEAN(a) (NCT05581303)
-
Pelacarsen, another Lp(a)-lowering therapy not previously mentioned, is also undergoing a phase 3 trial called Lp(a)HORIZON (NCT04023552)
And as discussed elsewhere on the forum (do a simple search),
- Obicetrapib, an oral CETP inhibitor, cuts Lp(a) by a lot - and will potentially be approved for other CVD uses already next year or early 2026 (and if so you could perhaps get it off label)
1 Like
Thank you. I actually took it a step further and sent the lead investigator of the JAMA article an email. He informed me that Eli Lilly is entering Phase 3 with lepodisran and they are taking names for people to apply for this clinical trial, which I did. Hoping they accept me and that I do not receive a placebo!
4 Likes
AnUser
#208
https://xcancel.com/Drlipid/status/1870629961377153333#m
So it appears according to Drlipid that non-Apo(a)-LDL’s decrease with statins is between one or two orders of magnitude more than the Lp(a) would increase with statins.
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