Is anyone here on or investigating PCSK9 inhibitors?

#42

PCSK9i isn’t zero risk btw but if my ApoB is high enough - I would have taken them even if it was triple that price. Personally, I will probably take them sparingly in specific situations since it’s injections only for now, but it depends on the situation. Reason is I am not certain enough for the bile acids and colon cancer association. Note that response is variable by individual assuming no immunogenicity.

I would most likely have taken them if they were oral, but unfortunately we aren’t quite there yet besides some initial data for berberine. There are a bunch of potential PCSK9i naturally though.

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#44

Get a concierge physician - the ones who really care tend to offer extraordinary low preferential “wholesale” pricing on labs

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#46

OT

VERY interesting timing of your post. When I replied I considered going into my medical vacation testing experience in… Thailand! Then I considered starting a thread about it when I have more time (I’ll duplicate this post in a new thread, as I think it’s probably a topic of interest).

My experience with medical tests/exam packages in Thailand is mixed, and I don’t really trust my results like I did before. In fact, I’m going to pay to get my CAC redone here in the US just to be sure (having to pay for it because I’m treated like a hypochondriac when I bring it up to a Dr).

Thailand has very good (and VERY efficient) health care. That said, the medical exam side is an assembly line of check-up packages for tourists where quality, well… isn’t. It’s the most junior/least competent doctors (if you think about it, this makes sense- top doctors aren’t doing physicals all day, every day). The exams are rushed and far from thorough and the tests are… suspect, at best. Examples:

  1. My “exam” was clothed until I had a talk with the doctor about what I had paid for. My body loves to make random tumors now and again (usually lipo), so when I had another bulge, that was my first thought. I showed it to the Dr- he said he had no idea what it was and referred me to an oncologist. Didn’t have time for that so saw a Dr when I got back to the US. It’s a textbook sports hernia requiring 20 seconds to diagnose! Wow, great doctor…

  2. As part of my package, I had an ankle brachial index done. It flagged me as advanced peripheral artery disease. Alarming. I do have edema issue, so I was very concerned, but also puzzled combined with a CAC of zero. I paid a different hospital to do another ABI and the results were also bad, but not as bad as the first (moderate).

I returned to the US and told the same doctor who diagnosed the hernia about my ABI results. Given my heart issues in the past (Afib and a fluke minor heart attack at 35!- when I was ripped with 7% body fat, btw. I digress…), she relented and ordered the test. The tech who did the ABI test in the US hospital saw the Thai results in my chart, my heart attack, etc. When the test finished I asked the verdict. He said, “The verdict is- don’t get tests done in Thailand!”. My ABI was perfect. He said they have no idea what they’re doing.

  1. As part of the same package, I had a scan of my Thyroid. Radiologist came back with several large nodules of concern. You guessed it- same test in the US showed inconsequential small nodules. Measurements by the Thai radiologist were off by a factor of 5.

I have had excellent medical care in Thailand (I’ve lived there for a total of about 2 1/2 years). Bumrungrad is a great hospital, but it’s getting very pricey to the point that you’re just paying tourist prices. It’s was much more reasonably priced and twice as good 20 years ago. All the English speaking/advertising hospitals are similar. As you see from your link above, their CAC is 50% more expensive than you can find in the US.

So, I can’t recommend the Thai physical exam factory. I imagine all the blood work was correct and I hope everything else was- but the thing is, based on the above, I have no idea. The whole idea behind paying for this level of physical exam is to catch thing early and, also, to provide peace of mind. Neither box gets checked when you can’t trust the aptitude of both the technician (or pretend “tech”) doing the test, or the radiologist reading the results. I had 2 false positives and a missed diagnosis that any competent doctor (or nurse) would know. Of course, my concern is any false negatives…

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#47

The link showed $159.00 USD for a CAC.

Where in the US do you pay less for a CAC?

#48

Are there any differences people here notice between a weekly dose (140mg) and a monthly dose (420mg) when it comes to efficacy/side-effects?

Also, I’m curious if any of you have used Repatha on-and-off? All things being equal, how long do you think it’d take for LDL-C to return to earlier high levels after stopping Repatha?

#49

I was on Repatha and then changed to Praluent this year per insurance requirements, but I can’t answer your questions. Have you looked at the full prescribing info for time course of lipid lowering effects?

#50

I have FHC (total cholesterol always in the mid 300s). I’m on my third year of Repatha Sureclick 140. The first two years my numbers were excellent. This year however my LDL numbers took a major bounce upwards and I crossed back into the high range. I haven’t seen my cardiologist to talk about this yet but perhaps my body has developed anti-evolocumab antibodies.

Anyone else have a similar experience?

#51

Interesting! I haven’t heard of these meds stopping working, but your antibody hypothesis seems quite reasonable in the absence of obvious changes to diet or other cholesterol meds. Hopefully changing to Praluent or inclisiran will get you back where you need to be.

#52

So, some kind of tolerance to repatha develops?
That’s very interesting, and may have (either positive or negative) implications with use of rapamycin if it involves the immune system.

#53

It’s probably a very rare phenomenon, unlike what we normally think of “tolerance”.

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#54

One additional data point. After starting Repatha my LDL calc plunged from 195 to 7. This is with 20 mg Rosuvastatin also. I tried cutting out the statin for a couple months, and LDL rebounded to 78. Below 40 is preferable for plaque reduction. So I would recommend taking statins with Repatha to get the best result.

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#55

I’ve been trying to convince my doctor to give me Repatha without going through a statin first. He initially resisted, but last visit he told me another one of his patients (who was also a doctor) had convinced him, so he was no willing to do it.

Since my cholesterol numbers are “normal” (ApoB fluctuates between 80 and 100), he suggested that instead of taking the full 420mg dose, I take 70mg once every second week. I just draw it out with a syringe instead of using the automatic applicator. I just started this two weeks ago, so don’t know what my numbers will look like yet.

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#57

We don’t believe that’s what’s happening (yet). When my LDL dropped to the target range, I stopped taking ezetimibe and so this may explain why my LDL went up. I’m doubtful though because dietary cholesterol isn’t supposed to contribute to LDL very much.

In any case, I’m resuming ezetimibe, changing from the 140 mg/two week dose to the 420 mg/month dose, and initiated Ozempic. All three changes were made at the same time so I can’t really draw any conclusions for now.

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#58

Interesting. One reason I was recently reconsidering my beliefs about dietary cholesterol and its impact on LDL-C is that ezetimbe works. Perhaps it acts in multiple ways and reduces LDL-C even while fasting. But i need to read up more about this.

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#59

Yep it’s rare but not analogous to tolerance. Wouldn’t be particularly concerned in general.

#60
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#61

Yeah ezetimibe is not as well known beyond intestinal inhibition. Low-dose rosuvastatin (once weekly) + low-dose ezetimibe can be like <$10/month if one really stretches it with pill-cutters with a bulk of the LDL-lowering effects at relatively low doses.

Pretty unlikely to get myalgia (assuming pharmacogenetics check out) & probably negligible negative cognitive effects if any (no BBB). The main trade-off is a slightly increased potential for diabetes but uncommon. Some minor rare ones as well. May be worth considering talking to doc according to ACC 2022 guidelines, especially if one is already at higher risk in the first place with multiple risk factors.

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#62

Yes it does appear like there’s more to it based on those results in vegetarians.

It’s plausible that even the 10-15% of dietary cholesterol that does reach the serum has a big enough impact for some more than others due to the FH genotype(s) (meaning the limited liver enzyme activity results in faster accumulation in the blood).

Some relevant info about the mechanism of dietary cholesterol absorption.

#63

Here’s a helpful tool if you want to dig into your genotype. Rhonda Patrick’s site gives you a free report by uploading your 23&M raw data. Scroll down for the free ones:

#64

I have been on Crestor 20 mg and 10 mg of Zetia for the last year or so. My last blood test right before i got a heart stend for an 80% blockage of my LAD artery showed that my ApoB was 62, my LDL-C was 55, my Lipo-a was 12, LDL-P was 982m, sLDL-P was <154, HDL 57, and triglycerides was 137.

But probably because of my blockage my cardiologist put me on Repatha Pushtronex monthly injections of 3.5 mL

He wants to push my LDL even lower…

I have just had my first injection and I am going to do my blood work again two weeks after my second injection. It should be interesting to see what happens.

I am going to have some confounding other variables going on having started rapamycin back which i guess could serve to push my lipid levels back higher. I also started taking Pycnogenol 200 mg and Gotu Kola 500 mg daily which hopefully serves to protect my arteries from plaque.

My insurance is paying for the Repatha and I got a discount card online which lowered the copay to $30.

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