#943

Good to know that the empirical data coming from this forum would tend to support efficacy for smaller doses, and congrats for the tiny value of LDL-C!

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#944

I just asked the pharmacist, he said that not only there is no guarantee of perfect homogeneity if an unsplittable (by design) pill is split, but this is true also for a single ingredient pill.
In a few words, we cannot require that a Zetia pill split in two provides exactly one half of the dosage per half-pill.

It also turns out that the homogeneity issue is well-known in the pharmaceutical industry. A small pill is like a volumetric sample drawn from the much larger volume of the mix.
I can only guess they have developed their own procedures with ensuing standards and regulations, as the following article suggests.
In a few words, that appears to be a pretty deep rabbit-hole we may perhaps ignore to dig into.

https://www.sciencedirect.com/science/article/abs/pii/S0378517321011790

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#945

Yes, thanks.
And the rosuvastatin was held constant at 5 mg.
So I went from rosuvastatin 5/ezetimibe 10 mg to rosuvastatin 5/ezetimibe 5 mg. And there was no change in LDL-C at about 30.
This is in line with what has been posted about ezetimibe being as effective at 5 mg as at 10 mg.

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#946

Berberine promotes rosuvastatine uptake. Since I’m planning to use berberine in my scheme (because of potential glycaemic control) I’m considering other combos, even if less powerful, like Simvastatin/ezetimibe 10/10 mg.

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#947

I wouldn’t rely only on an obscure Chinese paper to make decisions for your health.

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#948

Also, just to play the devil’s advocate: the low-dose strategy is perfectly relevant for cost cutting. It can also lower known adverse events for the same LDL target (for instance the risk of diabetes with some statins). But could it also lower potential beneficial side effects?

For instance (and for the sake of the argument, no matter whether the article is correct or not), this paper suggested that ezetimibe might lower the risk of Alzheimer’s: Ezetimibe Reduces Alzheimer's Disease Risk (study)

The authors note that: “While these benefits may have been assumed to be secondary to cholesterol reduction via sparing of vascular inflammation, our human-cell-culture and intact-nematode experiments support a direct neuroprotective effect via disruption of aggregate-specific protein interactions.”

So ezetimibe might be protective via an off-target pathway independently from LDL reduction. If correct, is this neuroprotection dose dependent? If so, one might argue that 20 mg of ezetimibe is even better! (again, I don’t say that’s the case, just theoretically it could be)

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#949

I would agree with your suggestions, although, since berberine has been a part of the traditional chinese and Ayurvedic medicine, it’s maybe obvious that the Chinese and the Indians tend to study more this plant-derived principle.
I’m not able to judge if the substance of the article is reliable enough, although formally it would appear pretty good. I also concur that it would be best if there were more articles on this subject. I also read the literature on the IMPROVE-IT study and relative comments. I’m not 100% convinced, but a choice must be done.
At the end, this choice may turn out to be conservative on the side of safety although less effective on the side of results.
Last, and I did not mention it before, the issue is not just berberine. My GP won’t give me a prescription because these preventional strategies are not contemplated in the guidelines.
The specialist I know, a friend of mine, will give a prescription but has suggested Vytorin (with simvastatin) instead of Rosumibe (with rosuvastatin) because he’s taking this combo without problems after consulting with a cardiologist.
So, in this specific and personal situation, the easiest way now would appear to settle on Vytorin and potentiate it with berberine. I can always change if results are not as desired.

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#950

The lack of good research on non patented compounds is indeed very sad. But as you mentioned you were risk averse and because well studied and affordable alternatives exist (namely statins, ezetimibe and bempedoic acid), I see no reasons to use berberine. The availability is a good point: you can buy anything from IndiaMart and you can get a prescription for anything with EU Doctor (or any other doctor in Europe actually).

Coming back to the general topic of cardiovascular health, a new paper comparing statin + ezetimibe vs high intensity statin alone: Safety and efficacy of moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: A meta-analysis

The combo is better for LDL reduction and achieving target. For MACE, not statistically significant, but only 3 studies looked at that and the OR might still be in favor of the combo: “Lastly, MACE were evaluated by three studies, encompassing 4568 patients, and a non-significant difference in occurrence was found, with an OR of 0.54 (95 % CI [0.14; 2.11]; p = 0.373; I² = 53 %)” And: “Also, no difference was observed with respect to drug intolerance (OR 0.75; 95 % CI [0.32; 1.78]; p = 0.515; I² = 38 %) (Fig. 3C) or drug related adverse events (OR 1.20; 95 % CI [0.78; 1.84]; p = 0.404; I² = 0 %) (FIg 3D).”

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#951

The average OR looks good, were it not for the vast variability in the 95% CI…

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#952

Yes but check Fig 2 F: the wide OR is due to Choi 2023: a small study that found no difference (1 MACE in each group). If you remove it, the OR might become statistically significant in favor of the combo. This is cherry picking but it’s just to say that the trend looks good. We need more studies looking at combo vs single statin therapy to conclude definitely on this though.

#953

adssx, I think the cherry picking (discarding outliers or suspicious values), is acceptable when attempting to reach an objective conclusion and not just pushing an agenda.

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#954

I agree. I just wanted to be clear for those reading us that for now there’s no definite answer as to whether ezetimibe + low or medium dose statin is better than high intensity statin alone in terms of outcome.

Thankfully, several ongoing trials are looking at this question: ClinicalTrials.gov

We’ll have to wait a few years to get the results though… In the meantime we have to rely on the above…

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#955

Effect on LDL up to 40 mg ezetimibe:

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https://x.com/Drlipid/status/1823755001422078178

Atorvastatin is generally considered the first choice.

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#956

Yes, I’m just reading the details now and unfortunately the improvements in the combo with respect to simple statins are statistically significant but not that glamorous in average

LDL-C reduction (Mean Difference (MD) -5.05 mg/dL; 95 % CI [-9.02;-1.07]

Also, ApoB seems unaffected by the combo with respect to the control…

I wonder if there are in commerce reliable devices to check lipids with a finger prick and reactive strip, this would be the best strategy to ascertain on an individual basis the results.

#957

Yes tiny LDL difference but big difference in % of people who reached the 70 mg/dL target.

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#958

Note: thread title is “2019” but the study discussed below is brand new, published in Circulation 8/21/24

I thought this is worth cross posting. Attaching CVD through anti-inflammatory pathways using low dose colchicine appears to be a great option to decrease risk after maximally lowering ApoB. I’ve been on the fence, but this new study pushed me to go ahead and ask my PCP for colchicine Rx.

#959

There is danger in extrapolating an effect of a medication in disease to individuals without disease. Trivial example: two patients with a life threatening bacterial infection - one of them is given a powerful antibiotic and survives, the other one dies. So a paper is written: survival advantage of Powerful Antibiotic. And then longevity fans all start taking Powerful Antibiotic and disaster results.

Drug extends life, has good effect in people with a given disease? I don’t have that disease, should I take it for my health/longevity? That’s the question. Why do I like ITP trials? Because they’re in healthy mice. Not like those studies where they use genetically messed up mice give them “SPECIAL DRUG” to compensate for that particular mess, then declare “life extending benefits of special drug” and we all immediately take it even though we don’t have the mess condition. Here’s my longevity recommendation: pillow taped around the body - my proof, in my experiment, I smashed mice with a hammer, but the ones wrapped in pillows had a survival advantage. Ergo, we should all wrap ourselves in pillows. But ITP studies are still in mice - people, who knows.

Does this drug advantage healthy people, based on studies in sick people?

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#960

Are you talking about colchicine? I doubt such a study will ever be done in humans, but for those of us at high risk due to genetics (Lp(a), FH, etc) this approach could be a real breakthrough. I’m not suggesting they put colchicine in the water supply.

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#961

I really find it hard to believe… at 1 mg, 1/10th the minimum commercial dosage, the effect is just about the same than at 10 mg. I wish there were a way to split the pill in tenths.

Why?

#962

The half life is 22h so you can split in two and take it every other day. It might be doable to split in 3, but the ezetimibe 10 mg pill is already so small…

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