#23

I am not talking injury, just impaired function. But never gave much thought to Bempedoic acid as it is quite expensive in EU out of pocket and I would not qualify for a insurance prescription.
Still what I read did not convince me, but nothing really does for primary prevention in low risk individuals rather than lifestyle and enough omega 3 in diet.
And this effect of 15% reduction in apoB does is probably not worth any potential risk even though it as a better sounding name than statins with all the controversy and pro and con camps.

#24

Unfortunately I donā€™t have much of a choice. Bempedoic Acid and Ezetemibe is what I can get affordably from India. PCSK9i are too expensive and I am intolerant to statins.

Weā€™ll see how effective it is for me in late March when I get tested next.

I do like that BA is a targeted drug that lowers LDL, ApoB and CRP. It also activates AMPK and increases insulin sensitivity. These are all fantastic effects.

6 Likes
#25

Do you think the effect would be beneficial for longevity?

#26

What is your baseline apoB?

#27

My baseline ApoB is 102 which is high. I never had a problem with high cholesterol until I started taking Rapa. I didnā€™t do an ApoB test until after starting Rapa so I donā€™t know what it was before.

My LDL shot up 50% though on Rapa from 81 to 122.

#28

I have put the paper on my reading list.

3 Likes
#29

Have you had your ASCVD risk assessed? DO you have any other risk factors?
Have you tried lowering it with lifestyle interventions? The standard more fiber, less saturated fat diet? Losing extra weight? Dropping your BF down to around 10%? Physical activity? etc.

ps If you have your standard lipid panel you can calculate and approximate apoB here is one such tool https://jscalc.io/calc/QaltoCGzlT7FTf3j

1 Like
#30

I eat a pretty healthy diet. I am losing weight, but not fast enough. I think I need BA to counter the lipid imbalance from Rapa. Iā€™m committed now with a 6 month supply.

I had an arterial scan done by ultrasound and there was no sign of calcification or ASCVD. Thatā€™s why I am being proactive.

3 Likes
#31

Yes, why not, six months wonā€™t do any harm. My apoB went from baseline of 60 to 84 on rapamycin than back to 78 and latest measurement was 58. But I eat CR(ON) all the time and my BF is around 10%. I suppose shutting down mTOR shuts down also organism need for cholesterol and thus the build up. Some dietary intervention might be in order, fasting or something around dosingā€¦ jsut thinking out loudā€¦ I will see how my new regimen of daily rapamycin affects my lipids in march. I have been testing this new protocol since September.

Have you considered semaglutide aka Ozempic?

1 Like
#32

I donā€™t want to lose muscle mass. Iā€™ll continue with a slow loss. I am in no hurry. :slight_smile:

I think I will try empagliflozin before a GLP-1 inhibitor.

In studies, adult patients taking the 10 mg dose of Jardiance (empagliflozin) had an average weight loss of 2.8% from their baseline weight (their weight at the start of the study). Those receiving the 25 mg tablet had an average weight loss of 3.2% of their baseline weight.

#33

My husband takes Ozempic in low dose and with resistance training it is quite effective in weigh loss/management. All people I know that do resistance training with GLP-1i donā€™t have problems with muscle loss or building muscles.

4 Likes
#34

According to that paper (which may or may not be right) it appears to inhibit ACLY (in Liver cells?). I think inhibiting ACLY is bad for longevity as it reduces acetyl-CoA production at a very early stage.

I donā€™t know how many cells it will inhibit ACLY in and that is important as if it only inhibits acetyl-CoA production from citrate in liver cells it may have a balancing beneficial effect, but for me on that basis as far as I am concerned I donā€™t want to try it.

2 Likes
#35

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January 17, 2024

Impact of Bempedoic Acid on Total Cardiovascular EventsA Prespecified Analysis of the CLEAR Outcomes Randomized Clinical Trial

Results A total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients.

Conclusion and Relevance Lowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.

8 Likes
#36

How Will Our Practice Change After the CLEAR Outcomes Trial? 2024

Clinical registries of high cardiovascular risk patients demonstrate that at least 50% of patients fail to be treated with intensive statin therapy and that 50% of patients prescribed a statin will cease therapy within the next 18 months. Predictably, reduced adherence to statin therapy will have implications for suboptimal reductions in LDL-C and cardiovascular risk

I understand that BA+EZE leads to an equivalent LDL reduction as moderateā€“intensity statins without major side effects (in particular no risk of diabetes) and while also significantly reducing CRP: can we expect more and more people to switch to BA+EZE instead of statins? (beyond statinā€“intolerant and diabetic people I mean)

2 Likes
#37

@John_Hemming has a theory about acetyl-CoA, his protocol is partly about increasing it by increasing citrate. Bempedoic acid reduces this in the liver. What does John think of bempedoic acid at this stage?

1 Like
#38

The liver has different citrate transport proteins to most other tissues. I am not intending to take Bempedoic Acid so I have not given it a lot of thought. If it reduced citrate in other tissues I would be more concerned. The liver may not regenerate as well without the extra citrate.

2 Likes
#39

I donā€™t remember if activated bempedoic acid could make it to other tissues than the liver.

#40

At the core the basic function of the Genome is the production of proteins (with various complex systems of logic behind this). Anything that undermines this would cause me concern.

#41

Looks like there is a diminish return here similar for statins, so even low doses provide a lot of the total effect.

So for those of us who prefer not to use medicine from India there there might be a path where we just use a smaller dose.

The 40mg dose below is 22% of the standard 180mg dose in the US. So the cost would be a bit less than 1/5th. (Even 80mg dose would be 44% of the cost).

@AnUser and others what are your thoughts on a strategy along these lines? (As an adjunct/combination therapy to other Apo B lowering medicine(s)).

Monotherapy

Patients treated with bempedoic acid, 40, 80, or 120 mg, daily experienced a reduction in LDL-C levels of 18%, 25%, and 27%, respectively, compared with a 2% reduction in the placebo group (p<0.0001). Levels of atherogenic biomarkers apolipoprotein B (apo B), non-high-density lipoprotein C (non-HDL-C), and LDL particle number were significantly reduced in the bempedoic acid-treated patients compared to those who received placebo (p<0.0001). There was a trend of reduction in high-sensitivity C-reactive protein (hsCRP) levels in patients treated with bempedoic acid versus those treated with placebo (26% versus 2%), which was further amplified in patients with elevated hsCRP at baseline (43ā€“64% versus 7%).

4 Likes
#42

What are your best guess how much it will decrease apoB further as an adjunct to statins? or PCSK9 inhibitors?