Rilmenidine vs Telmisartan or other BP meds for Longevity

I take ramipril to lower blood pressure and have recently added the beta blocker propranolol in order to lower my resting heart rate.

I’m considering swapping the ramipril with something that has additional longevity benefits, beyond those associated with lowering blood pressure. My two candidates are Rilmenidine or Telmisartan, although I’m open to other options.

Anyone have an opinion on this or experience with either of these drugs?

References:
Rapamycin.news: Rilmenidine Extends Lifespan and Healthspan by 20%

Life Extension Magazine: Telmisartan, Best Drug To Treat Hypertension

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Would a BP of 120-130/70-80 be considered high enough to take Telmisartan?

The average telmisartan dose in monotherapy (73.5 mg) decreases SBP by 13.5 mm Hg and DBP by 8.7 mmHg per Treatment efficacy of anti-hypertensive drugs in monotherapy or combination. But you could take the lowest dose (20 mg) and get a lower reduction (that I estimated at about -10/-7, as it’s nonlinear). So with 120-130/70-80 and 20 mg telmisartan you might be fine. However, antihypertensive drugs show massive differences between individuals. For instance, the same paper says:

When the characteristics of the patients showing the overall best antihypertensive response were assessed, the associated variables were female sex, higher BMI, and Caucasian ethnicity, whereas Afro-American ethnicity and normal weight were associated with a lower response to antihypertensive drugs. Women experienced better antihypertensive response overall, and specifically to thiazides, ARBs, and combinations. Agarwal et al[5] also showed that women had better antihypertensive response to combinations (both, CCBs plus olmesartan and thiazide diuretics plus olmesartan) than men.

And your daily pattern matters as well. You don’t want to be in hypotension. Doing a 24h BP monitor might help to make the best decision. Telmisartan seems to be able to “smooth” your BP variability no matter your pattern, which, if true, would be a great thing: Effect of telmisartan vs. ramipril on ‘dipping’ status and blood pressure variability: pooled analysis of the PRISMA studies

Coming back to the OP’s question, most hypertension guidelines say that “antihypertensive medication should start with SPCs to ensure more rapid, effective BP-lowering” (source). SPC means “single pill combination” such as telmisartan/amlodipine. For instance, the 2023 European guidelines say: “Initiation of therapy with a two-drug combination is recommended for most hypertensive patients. Preferred combinations should comprise a RAS blocker (either an ACE inhibitor or an ARB) with a CCB or Thiazide/Thiazide-like diuretic. Other combinations of the five major drug classes can be used.”

So could you combine telmisartan and rilmenidine? I can’t find data on this…

Sartans are indeed interesting (see, for instance Candesartan inhibits Toll-like receptor expression and activity both in vitro and in vivo) but candesartan failed in the ITP. However, do mice die of hypertension? I don’t know :man_shrugging: It’s also interesting that despite the failure of candesartan, the ITP team decided to test another sartan: telmisartan (this time in combination with a statin). There’s a lot of positive longitudinal data on ARBs (see the related topic: Angiotensin II receptor blocker (ARB) experiences? - #8 by adssx ) and they seem safe. On the other hand, we just have one recent paper showing that rilmenidine extends lifespan in worms. This paper has only been cited 9 times so far. And there are two clinical trials ever registered!

(That being said, friends of mine recently looked at repurposing candidates for Alzheimer’s and they identified Debrisoquine, Guanethidine, Minoxidil, Doxazosin, Hydralazine, Sitaxentan, Pargyline, Reserpine, Bosentan, and Deserpidine as top candidates. Surprisingly, all these drugs belong to the same ATC category as rilmenidineGenerating new drug repurposing hypotheses using disease-specific hypergraphs)

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Conventional doctors diagnose hypertension when a patient’s readings exceed 140/90 . The scientific literature, however, indicates that the ideal range should be around 115/75 . Why Telmisartan Is Best For Blood Pressure - Life Extension

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The best use of things like Aktiia seems to be to monitor the effect/side effects of BP lowering meds.

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Although lower might be better… as in this discussion: Optimal Blood Pressure we Should Target? Systolic Under 110 or 100?

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Hypertension is diagnosed above 130 or 80 since 2017 in the US. Europe still has the old 140/90 guidelines but it may change this year (see https://academic.oup.com/eurheartj/article/43/35/3302/6661233 ). According to the 2017 US guidelines, the “normal” is below 120/80, which means 115/75 in terms of 24h average, see: Hypertension - Wikipedia .

So 115/75 is “normal”. The optimal may well be lower (or not :man_shrugging:) as RapAdmin said. Also, the intraday variability matters more than the mean. Could it be that what matters is “Time spent above 140” and that having a lower average like 110 ensures this? (random guess, not backed by anything)

100% Unfortunately they have the worst customer service in the world: Aktiia Reviews | Read Customer Service Reviews of aktiia.com I ordered last month. No news. I had to contact their boss on LinkedIn to get an answer that… They don’t know yet when they’ll deliver the Nov 2023 orders… Also: we need independent studies confirming that Aktiia works.

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IMO it’s a very good BP! Why to add another drug?

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Wow, that’s a long wait and you’re in the UK. I’m thinking of ordering and being in Canada I expect a longer wait. However, I did see a unit on Amazon and the promised delivery time seems reasonable.

I would guess that those on Amazon are the old models. I ordered the “new Aktiia” which is (supposed to be) waterproof, smaller and more accurate.

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Anybody figure out how to circumvent the country restriction to be able to download and use the Aktiia app in the US?

You can probably use a separate phone with the app store / google play store region set in a European country. The Aktiia app is free so you don’t need a European credit card.

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See this thread/post: Has Anyone Seen a Rise in Blood Pressure Using Rapamycin? - #239 by RapAdmin

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@ageless64 thanks for starting the thread. It made me look into how important is to keep BP low enough with current research.
I decided I would stay on Telmisartan and if needed use Amlopidine as a combination treatment. The optimal ratio of Telmisartan to Amlopidine is said to be 6: 1. Here is some research on Telmisartan:

Telmisartan is also unique in its ability to reduce fasting plasma glucose and increase adiponectin and insulin sensitivity (in addition to its anti-hypertensive properties)

And the fact that “The ITP is currently testing the ARB telmisartan, although in combination with atorvastatin. I find this a little odd considering they’ve tested neither drug in isolation, but at least a positive result would provide further support for telmisartan.” @jnorm

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I think they are trying to see if lower cholesterol and BP affects mouse longevity. I have a feeling it probably won’t as mice almost always die from cancer. However we know that LDL and BP do affect human lifespan. This is why mouse models don’t always apply to humans.

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Telmisartan alone and in combination can be ordered from India at very low prices.

Also statins can increase sugar levels while telmisartan increases insulin sensitivity so the combination could balance things out and have a neutral effect on glucose, while having positive effects on cholesterol + BP, in addition to telmisartan’s systemic benefits on mitochondrial and endothelial health. However, statin alone failed and sartan alone failed (candesartan, not telmisartan though), so the combination is unlikely to succeed, but it’s worth trying and if it does it may be informative about the potential of other combinations (GlyNac comes first to my mind) where (a + b combined) >>> (a alone) + (b alone).

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before you stop the Ramipril, read the Hope Trial
New Engl J Med 2000; 342:154-160 . The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and Micro-HOPE substudy.

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For blood pressure, lowering homocysteine also lowers blood pressure;

I have a MTHFR mutation which causes higher homocysteine levels;

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.114.013311

I started daily supplementing with methyl folate and trimethylglycine (as recommended by and my homocysteine went down, as did my BP.

Interesting, thanks. I have rs1801133(T;T) (homozygous for C677T of MTHFR = 10-20% efficiency in processing folic acid = high homocysteine, low B12 and folate levels) and a tendency to elevated BP as well :thinking:

Do you take 5-methyltetrahydrofolate (5-MTHF)?