Yeah, but I concider it a pain in the a$$ compared to the Omron wrist versions.
Have any of you use Candesartan? I was thinking to switch, but given that I just switched and up-dosed the telmisartan, I will wait. The thing is Candesartan is an inverse-agonist and block mechanotransductive signalling of angiotensin II receptor subtype-1 (AT1R), something the other ARBs do not do. This signalling (can) persists even if the AT1R is blocked, and is involved in cardiac remodelling.
Have you guys ever heard of compound 21? It is an highly selective AT2R agonist that I would like to use. But it only has a 4 hour half life, some off target effects (low-affinity antagonist of the thromboxane TP receptor), and would need to be special-order synthesized. There are some short lived peptides as well, but they need to be refined, like semaglutide has been, to extend its short plasma half life.
Haven’t used candesartan or really researched it, but recently I’ve been intrigued by olmesartan which is highly potent against HBP (most among ARBs) with a good safety profile and some really good recent data on effectiveness in lowering dementia risk and ACM in hypertensives. Reasonable half life. Another option you may want to look into.
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Note, that for people with both HT and T2DM, olmesartan looked very good compared to either candesartan or telmisartan, including renal impact. Older study and open label, but nice crossover design.
Difference in the effects of switching from Candesartan to Olmesartan or Telmisartan to Olmesartan in hypertensive patients with type 2 diabetes: the COTO study
“Data from all patients in the CO group (n=165) and the TO group (n=152) were analyzed. Clinic and morning home BP and urinary albumin levels showed a significant decrease from baseline at 16 weeks after switching to olmesartan in both the CO and the TO group (clinic BP, morning home diastolic BP, and urinary albumin, P <0.05; morning home systolic BP, P <0.01). In contrast, clinic BP, morning home BP, and urinary albumin were significantly increased again 16 weeks after switching back to candesartan or telmisartan (clinic BP, morning home diastolic BP, and urinary albumin, P <0.05; morning home systolic BP, P <0.01). No subjects experienced an adverse reaction that required withdrawal from the study. No adverse reactions attributable to the study drugs were observed.”
The more I study olmesartan, the more I like it!
But, then again an older study finds candesartan to be superior:
Effect of Switching from Telmisartan, Valsartan, Olmesartan, or Losartan to Candesartan on Morning Hypertension
But ultimately, olme noses ahead:
Comparative effect of candesartan and amlodipine, and effect of switching from valsartan, losartan, telmisartan and olmesartan to candesartan, on early morning hypertension and heart rate
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Hey Cronos, thanks a lot for this. I did my own lil research and it turns out that while candesartan is capable of stopping the mechanosensing stretch signal, which goes beyond just AT1R inhibition, it doesn’t bind AT1R in its ‘active’ form.
AT1R inverse agonism mechanism: ARBs stabilise AT1R in inactive conformation. Inverse agonists suppress not just Ang II-driven activation but also constitutive (ground-state) and mechanical stress-driven (stretch-induced) AT1R activation — critical distinction for aortic disease where haemodynamic wall stress is a constant stimulus independent of Ang II.
Active-state AT1R problem: When AT1R is already constitutively active, candesartan and telmisartan lose inverse agonist potency because their receptor contacts are altered in the active conformation. Olmesartan and eprosartan maintain full inverse agonism against constitutively active receptor.
This isn’t just about blood pressure anymore.
Now I have to try to explain to my GP why I want to switch again.
I wonder if a blend is a possibility?
A blend of what?
| Drug | t½ (hrs) | BP ↓ (approx) | Inverse agonism | Blocks stretch (mechanotransduction) | Active-state AT1R suppression | Notes |
|---|---|---|---|---|---|---|
| Azilsartan | ~11 | −14 to −20 / −8 to −12 | Very strong | Yes (robust) | High (likely preserved) | Highest potency ARB clinically |
| Candesartan | ~9 (active ~9–12) | −10 to −15 / −6 to −9 | Strong | Yes (well proven) | Moderate (reduced in active state) | Gold standard inverse agonist |
| Eprosartan | ~5–7 | −8 to −12 / −5 to −8 | Strong (unique binding) | Yes (good evidence) | High (preserved) | Distinct non-biphenyl ARB |
| Irbesartan | ~11–15 | −10 to −14 / −6 to −9 | Moderate | Partial | Moderate | Balanced PK/PD |
| Losartan | ~2 (metabolite 6–9) | −8 to −10 / −4 to −6 | Weak |
 Minimal |
Poor |
Surmountable antagonist |
| Olmesartan | ~13 | −12 to −18 / −7 to −11 | Very strong | Yes (robust) | Very high (preserved) | Best evidence for active-state control |
| Telmisartan | ~24 | −12 to −16 / −7 to −10 | Moderate–strong | Partial | Moderate–low | Longest half-life, PPAR-γ |
| Valsartan | ~6 | −8 to −12 / −5 to −8 | Moderate | Partial | Moderate | Dose-dependent effects |
I believe that the mechanotransduction signalling is an overlooked aspect of cardiac and aortic remodelling. It’s not just your blood pressure. I like the PPAR activity of telmisartan, but I will trade it for the mechanotransduction signalling.
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It is, but it’s dangerous since it increases mortality risks.
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