Thanks. No sources provided by Gemini so hard to comment. Telmisartan is indeed a great drug, probably the best antihypertensive. I’m taking 80 mg.
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That’s interesting. I am currently on 80mg/day of telmisartan and interested in 160mg. I was going to pair it with pioglitazone 7.5mg/day, but all my plans went out the window because of unexpected surgery coming up (ACDF) involving fusion of a couple vertebra in my neck with titanium plate and screws. The bone fusion is critical and can take up to 18 months. Since pioglitazone is a negative for bone health (suppresses osteoblasts, can enhance osteoclasts), I don’t want to risk poor bone fusion in my cervical spine. This means at least an 18 month delay of the pioglitazone for me.
Can you speak to your experiences/results of the 160mg telmisartan dose? Thx.
I too had a cervical fusion, except no Ti plates but bone graft from iliac crest. I had broken C5 and C6 at the age of 18! Anyways many moons ago!
I am afraid other than my potassium levels I cannot speak to anything. My BP did not change between 80 and 160 other than day to day fluctuations, nothing ascribable. Tell me what I should be looking for and I will respond. My Hba1c is around 7.2, had been as high as 12, but this decrease is due to Semaglutide and Tirzapetide. I am continuing with 160 because I did not experience anything negative and I can tolerate the added cost.
Among other good things, combining Telmisartan and an SGLT2 inhibitor creates a “bookend” geroprotective for aging kidneys. Telmisartan acts primarily at the efferent arteriole (glomerular exit), while SGLT2 inhibitors act at the proximal tubule and afferent arteriole (glomerular entrance). The two create synergistic hemodynamic and metabolic protection. It is a combination worth considering by older adults, including those whose BP is at least toward the middle of the normal range. My long term mean systolic BP was 118 before initiating telmisartan but the standard deviation was high. Adding 80 mg. Telmisartan lowered the mean to ~108 and significantly lowered the SD below the equivalence of the lower mean (another discussion but adding 250 mg. aged black garlic dropped my mean systolic further to ~104 – I’m leaving it there). Currently, I’m taking 5 mg. Canagliflozin but may increase that to 10 mg. at some point after re-assessing kidney function metrics.
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After controlling for major modifiable lifestyle factors such as diet and physical activity, ARB use was linked to a significantly reduced risk of dementia compared with ACEI use (hazard ratio [HR] = 0.72; 95% confidence interval [CI]: 0.65-0.80, p < 0.001). In exploratory agent-level analyses, compared with lisinopril, olmesartan (HR = 0.32; 95% CI: 0.16-0.62), candesartan (HR = 0.41; 95% CI: 0.24-0.69), telmisartan (HR = 0.42; 95% CI: 0.25-0.71), irbesartan (HR = 0.45; 95% CI: 0.27-0.75), and perindopril (HR = 0.52; 95% CI: 0.31-0.87) were associated with a significantly lower risk of dementia, while captopril showed a significantly increased risk (HR = 4.9; 95% CI: 1.04-23.4).
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Thanks for that study - no paywall! this is an Australian 250k cohort followed for 11 years. Also in there is a statistically significant reduction in all cause mortality with ARB vs ACEi. And what seems to be a decent look at compliance - an issue since ACEi have more annoying side effects than ARB so there could be a significant compliance effect on outcome.
Does make you wonder why everyone hasn’t switched entirely to ARBs?
The Captopril number is based on only 36 events and the confidence interval is so wide. They mention that in the discussion.
Also, all the various ARB confidence intervals overlap quite a lot. So their overall interpretation is class effect rather than any particular drug which seems reasonable to me. But then so much for talmisartan being unique here although I know there are other studies.
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The olmesartan signal is pretty interesting. Not even for the dementia effect, but the much bigger and in my eyes more significant effect of ACM. From the paper:
“All-cause mortality risk
Results indicated a significant reduction in the risk of death for ARB users compared to ACEI users (HR = 0.77; 95% CI: 0.73–0.82, p < 0.001). In exploratory agent-level analyses, olmesartan showed the greatest risk reduction (HR = 0.64; 95% CI: 0.56–0.74), followed by telmisartan (HR = 0.91; 95% CI: 0.85–0.97) and candesartan (HR = 0.92; 95% CI: 0.86–0.98) compared with irbesartan (Table S9).
ARBs showed varied mortality risk compared to lisinopril. Olmesartan was associated with the greatest reduction in mortality risk (HR = 0.34; 95% CI, 0.24–0.48) (Table S9). Perindopril was linked to the lowest risk of death among ACEIs (HR = 0.70; 95% CI: 0.50–0.86) compared with lisinopril (Table S9). After excluding patients whose hypertension diagnosis was based solely on AHM records, ARBs were significantly associated with the reduction of all-cause mortality compared with users of ACEIs (HR = 0.80; 95% CI: 0.75–0.85) (Table S9).”
For dementia the HR difference between olmesartan and telmisartan is a more modest 0.32 vs 0.42, but look at that giant chasm in ACM - 0.64 vs 0.91! That is huge! And to me the most important aspect of this is not even the size of the difference, but the fact that in the case of the other ARBs like telmisartan the ACM lowering is barely there at 0.91, whereas the impact of olmesartan is a hefty, substantial, meaningful 0.64. You could almost say that olmesartan lowers ACM and telmisartan does not(of course we are talking comparatively here!). Again, all this is comparatively, important not to forget.
What good is it to natter on about ppar-gamma, glucose, lipid control and pleiotropic effects of telmisartan if it doesn’t lower ACM? Well, olmesartan may have no impact on ppar-gamma, but so what, it impacts what ultimately really matters, all cause mortality.
Of course, there’s a giant asterisk to all of this. The ACM effect here is observed in hypertensive subjects. Additionally, we don’t know if this is down to the BP lowering effect - and let us note, olmesartan is a more powerful BP lowering agent among ARBs than any other including telmisartan. And this - BP lowering size effect - was not controlled for in this study (Strengths and Limitations section):
“Finally, the lack of blood pressure (BP) measurements and longitudinal data prevented adjustment for differences in baseline BP, achieved targets, or treatment intensity. As BP management is central to vascular and brain ageing, class- or agent-specific dementia protection reported in this study should be interpreted cautiously without such data.”
Nonetheless olmesartan is an interesting drug, and deserves more attention from biohackers who mostly hyperfocus on telmisartan - ACM is what matters. I have posted about olmesartan before on this site, it has a different pleiotropic profile than telmisartan, and slightly more side effects (though that’s not saying much, seeing as telmisartan has virtually none!).
Obviously nobody should make decisions about picking a drug based on one observation study, but the study can still identify a drug worth further exploration, in this case olmesartan. YMMV.
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Angiotensin II–Stimulating Antihypertensive Medications and Dementia-Related Neuropathology
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2844919
“In this cohort study with 756 decedents, cumulative angiotensin II–stimulating exposure was associated with lower risk for some types of neuropathology relative to angiotensin II–inhibiting exposure. Long-term angiotensin II–stimulating exposure (≥15 years) was associated with a 24% lower risk for arteriolosclerosis.”
“In this community-based autopsy cohort study, angiotensin II–stimulating antihypertensive medications were associated with lower risk of neuropathological burden, supporting findings from epidemiologic dementia studies. Additional mechanistic research examining the effects of individual antihypertensive classes on Alzheimer disease–related biomarkers is warranted.”
Another win for ARBs.
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For comparison some mortality and morbidity data for other HT med classes.
Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker
“A total of 32 804 participants (mean [SD] age, 66.9 [7.7] years; 17 411 men [53.1%]; and 11 772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22 754 participants (mean [SD] age, 68.7 [7.2] years; 12 772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]).”
I don’t know how to link, but table 3 is especially interesting, with ACM a big nothing in difference between these classes, which makes the ARB result in the other study quite interesting.
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Say more please… My BP was always between 105-110/65-75 until last year or so now it is usually 115-125/75-80 still good but I’d like to start a BP lowering drug. Did we establish which one of these drugs is best in terms of overall benefits (not just blood pressure lowering effects) with least side effects. I was thinking low doses of either Telmisartan, Captopril, or Nebivolol. Any insight is greatly appreciated.
I’d prefer an ARB like telmisartan if I only needed one med to bring down BP by a relatively small amount. Not medical advice, just what I’d do personally.
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