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Synergistic ARB + Nebivolol combination

Huehnerbruestchen

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Hey guys.

I found these articles and studies online and I wanted to share them with you.


So this one is about ARB long term use and aldosteron breakthrough within 6-12 months. So this can harm our kidneys and also reduce the effect of the used ARB if im right?

And furthermore there is another article about Nebivolol and it seems that Nebivolol not only prevents this aldosteron breakthrough but also they seem to be synergistic in the best way possible, meaning both can be taken in a low dose and we would see a much stronger reduction in BP and also prevent the long term aldosteron breakthrough.


Lowering the dose would also mean that most ARBs wont fuck around with potassium that much while maintaining the same blood pressure.
Sounds great to me. Is anyone taking that mentioned combination?
 

MyNameIsJeff

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I'm afraid that I know much less about this than nothuman gives me credit for. The RAAS is pretty darn complicated and mechanisms behind aldosterone breakthrough (AB) are not properly understood: https://www.medscape.org/viewarticle/561424_3

When we classify AB as the occurrence of supra-physiological levels of aldosterone (i.e. levels higher than typically in healthy people), then the incidence is as low as 10%. It is not unexpected that aldosterone levels would return to baseline levels following the disruption caused by an ARB, and is necessary to restore electrolyte homeostasis. This is in line with the finding that an increase in serum potassium levels due to the use of ARBs and lower sodium intake are predictors of AB. There is also no evidence that AB (however defined) leads to a decrease in kidney function:

[...] aldosterone breakthrough noted at 6 months did not predict the change in kidney function measures at 1 year (decline in eGFR or increase in albuminuria).

Further note that the effects of ARBs are only partially mediated through lowering aldosterone levels. Even when AB occurs, ARBs will still have BP-lowering and renoprotective effects. Furthermore, the incidence of AB appears to be independent of ARB dose:

Three studies directly addressed whether the incidence of aldosterone breakthrough was related to the dose or class of RAAS blockade. MacFadyen et al. enrolled subjects who were taking a variety of ACE inhibitors, normalized treatment to a bioequivalent daily dose of enalapril, and found no association between dose of ACE inhibitor and incidence of breakthrough.[6] Similarly, Tang et al. found no significant difference in the incidence of breakthrough between groups of patients randomly assigned to low-dose or high-dose enalapril.[29] Horita et al. found equal rates of breakthrough among subjects on ACE inhibitors, ARBs, or a combination of both.[31]

With that being said, there is solid evidence that lower aldosterone levels have benefits on their own. To the extent that Nebivolol achieves this, it is another good reason to take. But I believe that the effects of ARB+Nebivolol are additive rather than synergistic. They are both ideal drugs to take for bodybuilders, regardless. As pointed out above, there is no reason to try to limit the ARB dose since there is no relationship between dose and AB occurrence. I would take as much of Telmisartan and Nebivolol as necessary to achieve acceptable BP levels. A standard dose combination would be 80mg Telmisartan and 5mg Nebivolol. Some people (especially when on TRT or on a cruise) may already achieve satisfactory results on 40mg Telmisartan + 2.5mg Nebivolol. It does make sense, however, to periodically check Potassium and Aldosterone levels as part of one's blood work when using ARBs, just to be on the safe side.

The user gotgame on here was the first to advocate the use of Temisartan+ Nebivolol, I suggest you search his posts.
Also see this thread for more information about these 2 drugs: https://www.professionalmuscle.com/...maintaining-heart-health-while-on-aas.142419/
 

Huehnerbruestchen

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Hey Jeff,

appreciate your reply. And also thank you for linking me that thread. It seems that nebivolol and telmisartan make a good match. Also from what I found in studies online is that nebivolol is one of the only beta blockers matching with amlodipin and can certainly decrease blood pressure without bringing any side effects to the table beside the harsh blood pressure reduction (only this combination seemed safe if anyone wants to try this like me).

Really good forum here guys and so much information on here. (y)

So my next try will be to lower my Telmisartan dose from 60mg to 40mg and to also bring down my amlodipin from 5mg to 2,5mg and see if I can get the same or even greater bp reduction by throwing in some nebivolol low dose.

Telmisartan is really superb in regards to heart health and all the other benefits that it brings to the table.
 

madg

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I'm afraid that I know much less about this than nothuman gives me credit for. The RAAS is pretty darn complicated and mechanisms behind aldosterone breakthrough (AB) are not properly understood: https://www.medscape.org/viewarticle/561424_3

When we classify AB as the occurrence of supra-physiological levels of aldosterone (i.e. levels higher than typically in healthy people), then the incidence is as low as 10%. It is not unexpected that aldosterone levels would return to baseline levels following the disruption caused by an ARB, and is necessary to restore electrolyte homeostasis. This is in line with the finding that an increase in serum potassium levels due to the use of ARBs and lower sodium intake are predictors of AB. There is also no evidence that AB (however defined) leads to a decrease in kidney function:



Further note that the effects of ARBs are only partially mediated through lowering aldosterone levels. Even when AB occurs, ARBs will still have BP-lowering and renoprotective effects. Furthermore, the incidence of AB appears to be independent of ARB dose:



With that being said, there is solid evidence that lower aldosterone levels have benefits on their own. To the extent that Nebivolol achieves this, it is another good reason to take. But I believe that the effects of ARB+Nebivolol are additive rather than synergistic. They are both ideal drugs to take for bodybuilders, regardless. As pointed out above, there is no reason to try to limit the ARB dose since there is no relationship between dose and AB occurrence. I would take as much of Telmisartan and Nebivolol as necessary to achieve acceptable BP levels. A standard dose combination would be 80mg Telmisartan and 5mg Nebivolol. Some people (especially when on TRT or on a cruise) may already achieve satisfactory results on 40mg Telmisartan + 2.5mg Nebivolol. It does make sense, however, to periodically check Potassium and Aldosterone levels as part of one's blood work when using ARBs, just to be on the safe side.

The user gotgame on here was the first to advocate the use of Temisartan+ Nebivolol, I suggest you search his posts.
Also see this thread for more information about these 2 drugs: https://www.professionalmuscle.com/...maintaining-heart-health-while-on-aas.142419/

Any advice on when to dose ? Morning,night ? Or irelevant ?

I not use anything for BP and never needed to but i love learning

Thank you jeff for all your knowledge
 

jaxino

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I am on 40mg Telmisartan ed which is a minimal dose.... My creatine never went over 0,8 since i use it... Tren or not.
My bp on 700 test 875 EQ 350 Tren 350 mast is 70 over 120 on Telmi... Without it can go higher. I am 108kg at 10-12%bf since October, weights fluctuates a bit due to my hgh and slin experiments.

Tbh if you need some bp control you should think about using an ARB and not a betablocker.

I used 5mg Nebivilol instead of 40mg Telmi ed for a month and i was very very very lethargic, bp was a bit lower but it hit me mentally very bad.

I did some research and it seems that 20mg Valsartan+15mg Pioglitazone will be better than using Telmisartan but i am still waiting to receive pioglitazone.... It's very hard to source here in my country since it's Hospital only.
 

Huehnerbruestchen

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For some 40mg Telmisartan wont do much. And even 80mg wont do enough regarding blood pressure thats why some have to add nebivolol. Or any other component. Nebivolol just seems to make a good match besides amlodipine or hctz.
 

Bobik

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I am on 40mg Telmisartan ed which is a minimal dose.... My creatine never went over 0,8 since i use it... Tren or not.
My bp on 700 test 875 EQ 350 Tren 350 mast is 70 over 120 on Telmi... Without it can go higher. I am 108kg at 10-12%bf since October, weights fluctuates a bit due to my hgh and slin experiments.

Tbh if you need some bp control you should think about using an ARB and not a betablocker.

I used 5mg Nebivilol instead of 40mg Telmi ed for a month and i was very very very lethargic, bp was a bit lower but it hit me mentally very bad.

I did some research and it seems that 20mg Valsartan+15mg Pioglitazone will be better than using Telmisartan but i am still waiting to receive pioglitazone.... It's very hard to source here in my country since it's Hospital only.
why do you want to change what works for you? Telmi is fine, isn't it?

what are the benefits Valsartan + Piogli? Thnx
 

MyNameIsJeff

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Aims
The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.
Methods and results
In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio—adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event—of the primary CVD outcome [0.55 (95% CI 0.50–0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34–0.56)], myocardial infarction [0.66 (0.52–0.84)], coronary revascularization [0.60 (0.47–0.75)], heart failure [0.58 (0.49–0.70)], and stroke [0.51 (0.41–0.63)].
Conclusion
Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.
 

warlock

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Nothuman and MyNameIsJeff,

I appreciate the info you both shared regarding BP meds. I wasn't aware that taking this med before bed would bring better health benefits than if one takes it in the AM. How about if one is on both nebivolol and telmisartan? Would it be wise to take both before bed too?
 

Huehnerbruestchen

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Wouldnt I get the benefits of both worlds, if I split my bp meds into half and take them in the morning and also before bed?
Its also what the doc told me when taking higher doses, to split them up.
 

MyNameIsJeff

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In the study, all BP-lowering meds (if multiple were used) were taken at the same time (either before bed or in the morning).
[...]either ingestion of the entire daily dose of ≥1 prescribed BP-lowering medications of the major therapeutic classes (ARB, ACEI, CCB, β-blocker, and/or diuretic) at bedtime (bedtime-treatment regimen; n = 9552) or ingestion of all of such medications upon awakening (awakening-treatment regimen; n = 9532; Figure 1). Participating primary care physicians were allowed to prescribe without restriction any BP-lowering medication approved by the Spanish Agency of Medications and Health Products for once-daily dosing from any of the five listed recommended therapeutic classes as first-line therapy for untreated participants and as combination therapy for uncontrolled patients (those above target ABP thresholds). Dual and triple therapies were prescribed, when available, in single-tablet fixed combinations to improve adherence. The protocol required avoiding division of prescribed medications for ingestion as split doses, e.g. one-half upon morning arising and other half at bedtime. Thus, individuals of the bedtime-treatment group ingested the entire daily dose of the medications at this time and not a portion of one or more of them also in the morning.

It was for the bedtime dosing that reduced CVD morbidity and mortality (and improved kidney markers, btw) were observed. Since no comparison to a (morning/bedtime)-split dosing scheme for multi-drug regimens was made, we cannot say whether that would be better or worse. But based on our current understanding of the importance of adequate asleep BP control and the prevention of non-dipping, I'd speculate that taking all BP meds at bedtime should be better.
 

whacked

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In the study, all BP-lowering meds (if multiple were used) were taken at the same time (either before bed or in the morning).


It was for the bedtime dosing that reduced CVD morbidity and mortality (and improved kidney markers, btw) were observed. Since no comparison to a (morning/bedtime)-split dosing scheme for multi-drug regimens was made, we cannot say whether that would be better or worse. But based on our current understanding of the importance of adequate asleep BP control and the prevention of non-dipping, I'd speculate that taking all BP meds at bedtime should be better.

MyNameisJeff
Awesome contributions. Than you

What is dipping and non-dipping?
 

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