Angiotensin II receptor blocker (ARB) experiences?

[Neo]

The main point throughout has been around the following, can you please help clarify as I thought we had aligned and then from your last message I’m no longer sure.

You later said *“more likely”. Do you agree that that is a better way to characterize the level of certainty / can we agree that “for sure” based on longitudinal data you provided is too strong or are you saying that you believe “for sure” based on longitudinal data is actually correct?

[adssx]

Again, this is what I wrote:

So for telmisartan some effects are for sure independent of BP control. Telmisartan reduces insulin resistance and tumor necrosis factor alpha (TNF-alpha), it is a PPAR inhibitor and it clears alpha α-synuclein in some models.

The “for sure” relates to “some effects” and these effects are listed after (insulin sensitivity, PPAR-γ inhibition, etc.).

[Neo]

Your selective selection of this part of your message to quote and focus on is not fair:

@adssx

So for telmisartan some effects are for sure independent of BP control. Telmisartan reduces insulin resistance and tumor necrosis factor alpha (TNF-alpha), it is a PPAR inhibitor and it clears alpha α-synuclein in some models.

You are cutting out the whole sentence that “So” connects to.

“So” connects back to something - not forward to something.

You should include the top part also in here if you want to have a accurate representation of the issue.

@adssx

In longitudinal studies, from what I remember, people on telmisartan have 30% less AD and PD than people on other ARBs, who themselves have 20% less AD and PD than people on other antihypertensive.

So for telmisartan some effects are for sure independent of BP control.

Do you agree that “So” is referring back to what you said before “So” and especially that that is how many people would read or at least would risk reading it since that is language wise what it actually says?

[adssx]

@Neo

Do you agree that “So” is referring back to what you said before “So” and especially that that is how many people would read or at least would risk reading it since that is language wise what it actually says?

I’ve already addressed this here in my previous answer:

@adssx

It’s true that the “So” and the previous paragraph (about longitudinal studies) can make readers believe that it’s a conclusion. But I posted that at 7:35am while on the toilet (sorry for the details): can’t ask too much from me

[Neo]

Ok, that is all this was about - that “So… for sure” in the context of optimal blood pressure was too strong certainty/conclusion.

Now, onward and upward!

On my end, I’ll read up more on whether someone with optimal BP would benefit from Tel and what risks might be (and will try and get an Aktiia from Europe to stress test whether my BP in fact is optimal or not).

[Ziegelhausen]

Re: using EU Aktiia in USA:
I purchased the EU Aktiia and have been able to activate it in the USA with the following steps (for Android; hpefully IOS similar):

1. Download free VPN APP such as Windscribe
2. Create new google account; log in to that
3. Activate German VPN
4. Download Aktiia APP from new Google login and from within Germany VPN
5. Activate bracelet through App.
6. I was then able to log back into my normal Google account on my phone, and the App continues to work fine.

As an aside, Aktiia says they will be rolling out the bracelet in the USA in 2025

[desertshores]

@adssx

ARBs

Jeesh. This reminds other debates with @anuser and others on different topics in this forum.

No one is asking you to take telesmartan! If you think that there is a superior ARB take that instead!

Most self-prescribed users of telmisartan are also intelligent enough to keep track of their blood pressure and get blood work done regularly.

A retrospective analysis of 50 studies suggests that telmisartan has a tolerability profile similar to placebo:

The safety profile of telmisartan as monotherapy or combined with...

[adssx]

@desertshores

A retrospective analysis of 50 studies suggests that telmisartan has a tolerability profile similar to placebo:

Not only telmisartan btw, all ARBs: “A difference between ACEis and ARBs is their tolerability profile, with ARBs having a rate of side effects similar to placebo.” (2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension)

[Tim]

Does a BP med’s half-life have a bearing on its effectiveness as a BP medication? For example, telmisartan’s 24 hours against losartan’s 4.

[adssx]

Yes, that’s one of the reasons why telmisartan is the best ARB. Half-life matters because BP variability is as important, if not more, than mean BP for longevity. Guidelines recommend long-acting drugs to ensure efficient BP lowering over the whole day and night (and also in case you forget it one day or change the hour you take it). Besides telmisartan, the longest-acting dihydropyridine CCB is amlodipine and the longest-acting thiazide/thiazide-like is indapamide SR or chlortalidone.

[Tim]

Thank you the comprehensive answer. One more question. Would you say that idapamide is the most benign of the diuretics? I had a rough time with chlorthalidone.

[adssx]

This review indeed suggests that indapamide 1.5 mg SR has a better safety profile than other HCTZ and chlorthalidone (which themselves might have a better safety profile than other non-thiazide diuretics): Redefining diuretics use in hypertension: why select a thiazide-like diuretic? 2019

However, they cite old and/or small studies, so I’m not 100% convinced.

I find it more interesting that in many countries, such as Canada, the use of indapamide is slowly increasing: wisdom of the crowd? See: Prescription Trends of Thiazide Diuretics in a Canadian Primary Care Population from 2015-2021 2024:

Which chlorthalidone dose did you use? What is the dose equivalence between indapamide and chlorthalidone?

[Tim]

I took 25 mg of Chlothalidone, and my BP dropped like a rock. But it was hard to deal with. My GFR went down 6 points, my BUN went up 40, and I got a case of gout. Meanwhile, a mere 5 mg of amlodipine gave me pedema, a most unwelcome development for a runner.

I’m thinking of replacing the losartan with telmisartan, replacing the chlothalidone with1.25 mg or less of indapamide, and cutting the amlodipine from 5 to 2.5 mg.

I appreciate your extensive research into this subject. Have you delved so deeply because you struggle to control your own BP, or are you in the medical profession?

[Davin8r]

What about telmisartan along with an SGLT2 inhibitor such as empagliflozin or dapagliflozin instead of indapamide? You’d get a diuretic effect (mild and transient), but most importantly you’d get lasting effects of decreased glucose and blood pressure, possible modest body fat loss along with other potential health/longevity benefits. Might be worth considering with your medical provider (this is not meant to be medical advice).

[Tim]

Thanks for the suggestion @Davin8r. I’ll have to study the question further. I’ll read a little and then talk it over with my clinicians, although sometimes I make independent decisions. Rapamycin, for example.

[Ziegelhausen]

I’ve had good success with telmisartan 40mg and amlodipine 2.5 mg. I got pedema with amlodipine 5 mg, but it went away at 2.5. I also take empagiflozan 10 mg, but did not see an effect on BP from that. I’ve gotten my BP from low 120s systolic to my target of <115…

[adssx]

@Tim

Have you delved so deeply because you struggle to control your own BP, or are you in the medical profession?

I’m struggling to control my own. Usual disclaimer: I’m not a doctor and this is not medical advice. (In my case dapagliflozin 10 mg + telmisartan 40 mg + amlodipine 5 mg only reduced my 135 mmHg SBP by about 10 mmHg so I’m now considering indapamide 1.5 mg SR…)

I don’t think there’s any good reason to use losartan instead of telmisartan. Losartan does not reduce insulin resistance for instance. (I won’t cite sources because I’ve already posted them in this thread or the other one on telmisartan).

Amlodipine 5 mg combined with telmisartan has an edema risk barely higher than placebo: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172077/figure/f3-ibpc-4-027 So amlodipine 2.5 mg with telmisartan has probably a rate of edema lower than placebo. Another reason to ditch losartan for telmisartan.

SGLT2i such as empagliflozin or dapagliflozin can indeed decrease SBP but this is NOT a diuretic effect, stop saying this @Davin8r: SGLT2 Inhibition: Neither a Diuretic nor a Natriuretic and Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.

Regarding diuretics, I found this dose equivalence table: https://www.consultant360.com/articles/hydrochlorothiazide-hypertension-it-diuretic-choice

There hasn’t been large trials comparing indapamide to chlorthalidone so I think this table is mostly a guesstimate. It is still useful and it tells us that indapamide 2.5 mg won’t decrease BP more than the CTD 25 mg you tried. So you could try indapamide 1.5 mg SR (equivalent in BP reduction to 2.5 mg IR with lower side effects according to some paper). Please note that it takes three MONTHS for indapamide to reach its full effect on BP reduction.

You mentioned an eGFR dip: any drug that significantly decreases BP (including SGLT2i and ARBs that are renoprotective!) might cause an initial eGFR dip that normally bounces back to normal after a few weeks.

[adssx]

Just published in The Lancet: Antihypertensive medication classes and risk of incident dementia in primary care patients: a longitudinal cohort study in the Netherlands 2024

Compared to ACEi, ARBs [HR = 0.86 (95% CI = 0.80–0.92)], beta blockers [HR = 0.81 (95% CI = 0.75–0.87)], CCBs [HR = 0.77 (95% CI = 0.71–0.84)], and diuretics [HR = 0.65 (95% CI = 0.61–0.70)] were associated with significantly lower dementia risks. Regarding competing risk of death, beta blockers [HR = 1.21 (95% CI = 1.15–1.27)] and diuretics [HR = 1.69 (95% CI = 1.60–1.78)] were associated with higher, CCBs with similar, and ARBs with lower [HR = 0.83 (95% CI = 0.80–0.87)] mortality risk.
Moreover, a recent network meta-analysis suggested that specific AHM-classes, particularly angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs), reduce dementia risk beyond their BP lowering effects.
Dementia risk was similar within CCB subclasses (dihydropyridine/non-dihydropyridine), and within diuretic subclasses (thiazide/loop/K-sparing) versus ACEi.
Within diuretic subclasses, mortality risk was lower for thiazides (HR = 0.87; 95% CI = 0.83–0.93), and higher for loop (HR = 3.05; 95% CI = 2.89–3.22) and K-sparing (HR = 1.50; 95% CI = 1.42–1.59) diuretics versus ACEi
Among patients receiving AHM, ARBs, CCBs, and Ang-II-stimulating AHM were associated with lower dementia risk, without excess mortality explaining these results. Extensive subgroup and sensitivity analyses suggested that confounding by indication did not importantly influence our findings. Dementia risk may be influenced by AHM-classes’ angiotensin-II-receptor stimulating properties. An RCT comparing BP treatment with different AHM classes with dementia as outcome is warranted.
The lower dementia risks associated with ARBs and beta-blockers compared to ACEi slightly attenuated with increasing age. This may be a chance finding. Alternative explanations are speculative. Possibly, some classes, such as ARBs, rely more on neuroprotective properties that are particularly exerted before extensive neuropathological changes associated with late life dementia develop, thereby potentially extending their therapeutic benefits, especially in younger age groups. Alternatively, ARBs might particularly reduce the risk of dementia with (micro-)vascular origin, which could represent a larger proportion of dementia cases in younger patients.
Several hypotheses suggest how individual AHM-classes might reduce dementia risk beyond BP lowering effects. For example, dihydropyridine CCBs may prevent neuronal cell death and AD neuropathology by regulating cellular calcium influx, and ARBs may reduce inflammation, oxidative stress, and AD neuropathology by improving cerebral blood flow. The more recent “angiotensin hypothesis” suggests that several AHM-classes lower dementia risk by stimulating the angiotensin-II-receptors type (ATR) 2 and 4, involved in cerebral ischemia and memory function (Fig. 1). ARBs directly block ATR1, increasing ATR2 and ATR4 stimulation, and upregulating angiotensin-II production. Thiazide diuretics and dihydropyridine CCBs stimulate ATR2 and ATR4 by increasing renin and thereby angiotensin-II production. BBs and non-dihydropyridine CCBs decrease renin and thereby angiotensin-II production. Finally, ACEis inhibit angiotensin-II production, inhibiting ATR2 and ATR4, and may also decrease cerebral Amyloid-Beta degradation wherein ACE is involved. This would fit with ACEi generally being associated with the highest dementia risk, ARBs versus ACEi most consistently with lower dementia risk, and the consistent results of studies evaluating Ang-II-stimulating versus inhibiting medication, discussed above. Our results do not fully support the angiotensin hypothesis. This could be attributed to residual confounding within the observational data or to other, as-yet-unknown mechanisms that might also influence the differential associations between antihypertensive medication classes and the risk of dementia.
Moreover, a large meta-analysis reported that the association between blood pressure lowering with AHM and lower risk of dementia or cognitive decline was not affected by baseline blood pressure or cumulative systolic blood pressure change. Finally, in a different cohort with similar characteristics where BP values were available, we found no apparent differences in BP values between AHM-classes. Therefore, we expect that the differential associations in our study represent class-specific mechanisms affecting dementia risk beyond BP lowering effects.
ARBs, CCBs, and thiazide diuretics were associated with lower dementia incidence rates compared to ACEi-use, without excess mortality. Combined with previous studies, our study makes a compelling case for differential associations between AHM-classes and dementia risk, particularly for lower risks associated with ARBs versus ACEi and Ang-II-stimulating versus Ang-II-inhibiting AHM-classes.

The HRs are even better in those who started medication before age 60:

Quite an amazing paper!

Unfortunately, they did not address combinations well. So we don’t know if the effects are additive, and therefore the HR multiplicative, which, for example, would give, in the best-case scenario, for the combination of ARB + dihydropyridine CCB + Thiazide(like): 0.85x0.79x0.75 = 0.50 for dementia. If among each of these classes there is a best-in-class drug that reduces dementia risk even more and if the effects are still additive then we might have an HR for the combination as low as 0.3 (the proof is left as an exercise to the reader ).

[Davin8r]

@adssx

NOT a diuretic effect, stop saying this @Davin8r

It’s a diuretic for a short time, until counter-regulatory mechanisms kick in. It still lowers blood pressure. And there are ways to offer corrections/amendments without being patronizing.

[adssx]

@adssx

I dug more, almost all research papers on Aktiia are conducted by… Aktiia. One recent exception is Evaluation of the ability of a commercially available cuffless wearable device to track blood pressure changes. They found that the daytime average found by Aktiia was correct but that the night-time one was significantly off (+15.5 mmHg). They concluded: “This cuffless wearable device did not accurately track night-time BP decline and results suggested it was unable to track medication-induced BP changes.”

Aktiia answered: Inadequate study designs for the evaluation of blood pressure monitoring devices and their potential misleading conclusions - PMC

I find their answer unconvincing… They even “agree with the results showing that the nighttime dip measured by Aktiia was significantly smaller compared to ABPM”

A paper from this month by Aktiia themselves confirms that their device isn’t reliable during the night: COMPARATIVE EVALUATION OF THE AKTIIA CUFFLESS MONITOR AND STANDARD 24-H AMBULATORY BLOOD PRESSURE MONITOR

No significant differences were found between Aktiia and ABPM monitors in 24-h and daytime SBP readings (24-hour: mean ± SD [95% CI] 2.6±12.3 [-0.2, 5.4] mmHg, correlation r=0.57, P=0.06; daytime: 1.2±12.4 [-1.6, 4.0] mmHg, r=0.60, P=0.38). However, night-time SBP readings showed more pronounced differences (12.5±14.4 [9.3, 15.8] mmHg, r=0.39, P<0.001). DBP readings were significantly different but within clinical acceptance for 24-h and daytime (24-hour: -2.9±7.9 [-4.7, -1.1] mmHg, r=0.63, P=0.002; daytime: -3.1±8.2 [-5.0, -1.3] mmHg, r=0.64, P=0.001), with notable night-time differences (4.1±8.5 [2.2, 6.0] mmHg, r=0.57, P<0.001).
The findings reveal the Aktiia monitor’s promising performance in continuous, long-term BP monitoring, especially during daytime, while noting important differences at night. Further research is underway to investigate nocturnal measurements.

Another team (not Aktiia), published a paper in the same journal, this time comparing office measurements to the daytime average BP from Aktiia, and the figure doesn’t look great to me in terms of individual measures but it confirms that the average daily BP found is close to the office measurements:

Bland and Altman analysis revealed a difference of 0.015 (CI -0.734 to 0.763) in systolic BP and of 0.380 (CI -0.216 to 0.975) in diastolic BP (Figure 1). The agreement for the diagnosis of hypertension was 92.4% with a kappa of 0.61±0.04 for systolic BP and 94.7% with a kappa of 0.50±0.04.

---

This is really bad for 24h and night… But still reassuring for daytime measurements…