First report from Epiterna on the search for drugs that can extend human lifespan

[adssx]

Yes there might be confounders. For instance for viagra, I guess people who use it tend to be in a relationship, maybe a happy one, etc. They’re also probably not hospitalized.

[adssx]

@AnUser

I guess this study shows which drugs have an outsized effect when prescribed to disease process relative to healthy population?

No sure actually. Otherwise why would atorvastatin outperform while rosuvastatin and others failed?

[adssx]

@adssx

Do they plan to publish the whole dataset with the 400 tested and the 14 “winners”?

[…]

I’d like to see the results for lithium, GLP1RAs, and finasteride as well.

Actually, they did: Association between prescription drugs and all-cause mortality risk in the UK population | medRxiv

A few interesting things:

• Telmisartan is the only sartan with a low HR (HR all: 0.86 CI 0.56–1.32, HR males: 0.76 CI 0.46–1.25), but it didn’t reach significance, probably because of the small sample size, as it’s rarely prescribed in the UK (n=306 vs 7860 for losartan, for instance).
• Amlodipine is neutral (HR: 0.99, CI 0.95–1.04). In males, 5 mg (HR 0.98 CI 0.91–1.04) might be better than 10 mg (HR 1.06 CI 0.97–1.16). Lercanidipine is another interesting dihydropyridine CCB: HR 0.93 CI 0.77–1.12.
• They don’t give data for each flozin alone; they only group them (with a small total sample size n=563).
• Indapamide is interesting: HR 0.87, CI 0.756–0.999 but p=0.048 (poke @DrFraser you’ll like this). Contrary to thiazide: HR: 1.0. Indapamide 1.5 mg SR (HR 0.83 CI 0.66–1.04) might be a bit better than indapamide 2.5 mg (HR 0.89 CI 0.75–1.05). (Chlorthalidone is rarely prescribed in the UK)
• Finasteride: HR male: 0.94 CI 0.84–1.05.
• Pioglitazone: HR all: 0.91 CI 0.76–1.08 (30 mg is doing great in males: HR 0.74 CI 0.57–0.97).
• Liraglutide is the only GLP1RA listed: HR 0.81 CI 0.56–1.18.
• Lithium carbonate (but 400 mg!): HR 2.15 CI 1.22–3.80
• Sirolimus and other -rolimus drugs not listed.
• All statins:
  
  
• Ezetimibe: HR 1.11 CI 0.97–1.27 (similar HR among males only).
• Bempedoic acid and PCSK9i: not listed.

[Neo]

@adssx

All SGLTi seem to extend lifespan

This is great, I saw that they said “as a class”, did they also say “all”?

[adssx]

You’re right, they did not, I clarified that point after looking at the raw data: First report from Epiterna on the search for drugs that can extend human lifespan - #10 by adssx

[AnUser]

@adssx

But in the meantime, should people prefer atorvastatin to other statins?

@adssx

Otherwise why would atorvastatin outperform while rosuvastatin and others failed?

Atorvastatin has already been proven to be superior to rosuvastatin in terms of side effects, lower diabetes risk and cataract surgery:

Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial (2023)

The mean daily dosage was 36 mg for atorvastatin and 17.1 mg for rosuvastatin, meaning most were at 40 mg or 20 mg, respectively. It is promising that it showed fewer side effects in this study compared to rosuvastatin. What does @Virilius think?

So this more info in favor of atorvastatin. But has atorvastatin reduced all-cause mortality, which rosuvastatin has?

[desertshores]

I find it odd that Naproxen is on the list as I thought NSAIDs increased the risk of death.
“It is widely considered a strong painkiller and is part of the category of medicines known as non-steroidal anti-inflammatory drugs (NSAIDs).”

“Naproxen and other nonsteroidal anti-inflammatory drugs (NSAIDs) can increase the risk of heart attack and stroke”

“NSAID use causes an estimated 3,300 deaths and 41,000 hospitalizations each year among older adults.”
“NSAID use is associated with an increased risk of death after one year and five years.”

[adssx]

Yes, there are several surprising results.

For instance, they found HR 2.15 for lithium carbonate. And yet, another Swiss team looking at the same dataset (UK Biobank) found that “Subsequent multivariate survival analyses reveal lithium to be the strongest factor in regards to increased survival effects (hazard ratio = 0.274 [0.119–0.634 CI 95%, p = 0.0023]), corresponding to 3.641 times lower (95% CI 1.577–8.407) chances of dying at a given age for lithium users compared to users of other anti-psychotic drugs.” (Lithium treatment extends human lifespan: findings from the UK Biobank 2023)

[DrFraser]

I love that Nystatin made it in the statin’s list … this is actually an anti fungal for candida (usually use for thrush or vaginal candidiasis). Anyway, not a good one for aging apparently. But also not a cholesterol medicine.

[PolishGentleman]

@adssx

For instance, they found HR 2.15 for lithium carbonate

It may be because dose for longevity is much lower than for psychiatric illnesses
Doses of lithium for longevity purposes are about 20 mg / day, doses for illness are about 1800 mg / day - 90x difference

[adssx]

I’m sorry. It was my mistake. I simply filtered for “statin” in my spreadsheet. I’ll edit my message.

[LukeMV]

This one SHOCKED me. I’ve always felt so guilty whenever I took one if I had a headache or felt sick. Now I guess I don’t feel so badly about it. It also reduces pain before working out.

[LukeMV]

Well I guess I might have to ask my doctor to switch me from 5mg Rosuvastatin to 10mg Atorvastatin now.

[adssx]

@AnUser

Atorvastatin has already been proven to be superior to rosuvastatin in terms of side effects, lower diabetes risk and cataract surgery:

I didn’t know, so why do you take rosuvastatin then?

[AnUser]

I see no reason to switch right now to atorvastatin unless there is a large RCT that has showed benefit in all cause mortality like rosuvastatin.

[LukeMV]

Better question: If you were being prescribed statins for the first time and were given your choice of the two, which would you pick?

[AnUser]

I wrote more on rosuvastatin over atorvastatin here:

Rapamycin and risk of cardiovascular disease

I will do 10 mg rosuvastatin + 10 mg ezitimibe instead next. I chose rosuvastatin over atorvastatin: I already had success with rosuvastatin. It is not metabolized at CYP3A4 which mean I can try rapamycin later with GFJ, and also fewer drug interactions I guess. It being hydrophilic might give benefits. I can monitor diabetes risk anyway so it doesn’t matter that much that is has a higher causal risk compared to atorvastatin. Both Trump and Biden takes it. Peter Attia recommends it to start with.

Add in detected benefit for ACM for rosuvastatin. That’s much better. This is an association study. 10 mg atorvastatin had null effect in it.

I am thinking actually about skipping ezetimibe and going to high dose statins, because 20 mgs showed benefit in ACM in JUPITER.

[LukeMV]

Another thing I wonder.

I don’t see Tadalafil mentioned anywhere so I wonder if the mortality benefits were only seen with Sildenafil.

[adssx]

@LukeMV

I don’t see Tadalafil mentioned anywhere so I wonder if the mortality benefits were only seen with Sildenafil.

It’s in the supplementary material: https://www.medrxiv.org/content/10.1101/2024.03.08.24303967v1.supplementary-material

The problem is that they didn’t do the disambiguation between generic names and brand names correctly, so for instance the dataset lists:

• FENBID and IBUPROFEN
• Tadalafil (HR 0.86 CI 0.75–0.99) and Cialis (HR 0.77 CI 0.60–0.99)
• IMIGRAN and Sumatriptan.

If done correctly, this might change the results.

Something else that I don’t understand: Telmisartan HR in males = 0.76 but HR for telmisartan 40 mg = 0.80 and HR for telmisartan 80 mg = 0.82. How can the HR for telmisartan be lower than the one for each telmisartan dose?! I would expect HR (A+B) < min(HR(A), HR(B)).

Also, in drugs, there is “FREESTYLE TESTING STRIPS”…

Not reassuring on the quality of the paper…

[LukeMV]

Yea this is extremely interesting but there still seems to be so many flaws here. I also can’t for the life of me understand how viagra could have more health benefits than cialis when it’s so much shorter acting.