It’s unfortunate that blood pressure medication can’t only target systolic (to my knowledge). Most people don’t want to lower their diastolic since it could get too low. I know I’m one of these people who has to watch out for low diastolic.
Yes, isolated systolic hypertension (ISH) can be harder to treat: Unsolved Problem: (Isolated) Systolic Hypertension with Diastolic Blood Pressure below the Safety Margin 2020
The general recommendations for (I)SH treatment mostly agree in various international and national guidelines. They differ in terms of a class of recommendations and level of evidence, but most guidelines recommend thiazide(-like) diuretics and dihydropyridine calcium-channel blockers (CCBs). The Korean Society also recommends angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers as first-line drugs for (I)SH. Experts in Canada do not recommend α-/β-blockers as the first choice of antihypertensive drug for (I)SH unless there is a compelling indication. The authors of The National Institute for Health and Care Excellence (NICE) guidelines from Great Britain recommend the same therapy as for other patients with HTN.
The 2023 European guidelines say:
Based on the data in aggregate, CCBs and Thiazide-like diuretics emerged as the drugs of choice for the management of ISH, whereas ACEis/ARBs showed less efficacy, suggesting that they should be used as first-line agents when there are compelling indications such as HF, coronary artery disease, CKD, metabolic syndrome and diabetes.
See also: Isolated Systolic Hypertension: An Update After SPRINT 2016
Drugs to Avoid: Beta-Blockers
Evidence has shown that beta-blockers have little, if any, efficacy in management of hypertension.As noted in the isolated systolic hypertension substudy of the Losartan Intervention For Endpoint reduction (LIFE-ISH) trial, atenolol was inferior to losartan for cardiovascular risk reduction.In the second Swedish Trial in Old patients with Hypertension (STOP-2) trial subgroup, the combination of diuretics and beta-blockers had the highest events for stroke, compared with ACEi and CCBs.
It’s hard to get good data on how much each antihypertensive reduces SBP and DBP as it depends on the dose but also on the individual (men and women might respond differently, there might be differences between ethnic groups as well). For thiazide-like diuretics, this paper claims that indapamide 1.5 mg SR is better than amlodipine and candesartan: Indapamide SR Versus Candesartan and Amlodipine in Hypertension: The X-CELLENT Study 2006
For the patients with isolated systolic hypertension (n = 388), the three treatments significantly reduced systolic BP, but only indapamide SR did not change diastolic BP and thus reduced pulse pressure significantly relative to placebo (P = .005). […] In patients with isolated systolic hypertension (n = 106), indapamide SR reduced 24-h systolic BP significantly more than amlodipine (P = .037), and only indapamide SR reduced 24-h pulse pressure significantly relative to placebo (P = .03).
If you need even more BP lowering, another study looked at indapamide 1.5 mg SR (the sustained release version seems better than the normal indapamide 2.5 mg) + amlodipine (5 mg or 10 mg) and you can see that this combo is clearly the best at massively lowering SBP while keeping DBP in range: Effectiveness of indapamide/amlodipine single-pill combination in patients with isolated systolic hypertension: post-hoc analysis of the ARBALET study 2022
At study entry, 68.5% were prescribed indapamide/amlodipine SPC at a dose of 1.5/5 mg and 31.5% were prescribed a dose of 1.5/10 mg.
At 3 months, 60.7% of patients were receiving a dose of 1.5/5 mg, and 39.3% were receiving 1.5/10 mg
Unfortunately, they don’t give the results by dose, but I assume that 1.5/5 mg reduced DBP less than 1.5/10 mg and if that’s still too much you can use 2.5 mg amlodipine instead.
On a personal note, I’m actually considering adding indapamide 1.5 mg SR. Telmisartan 40 mg + amlodipine 2.5 mg reduced my BP only by -7/-6 mmHg to reach 127/75 (24h Aktiia), so although I’m not hypertensive anymore per Europe guidelines (<130/80), I’m still a bit higher than the US guidelines (<125/75) and I’m definitely not “optimal” (<115/75). Although it could have other benefits, pushing telmisartan to 80 mg won’t bring more SBP reduction. Increasing amlodipine to 5 mg is another option (FDA):
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For most patients - and there are exceptions, beta blockers come later once we’ve not had adequate success with the stepwise progression. I don’t like the blocking of maximal heart rate and potential effects in ability to exert oneself - if an elite athlete. There is a fair bit of controversy in that space.
Overall, seeing more patients get into symptomatic bradycardia with age must also be monitored.
There are situations such as heart failure where there are likely benefits - but for dual use for longevity and hypertension - I think there are probably better choices.
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If I look at the NICE recommendations they seem all over the place, has someone showed that telmisartan for example is recommended by medical societies over other treatments? It’s not as clear as is the case for atorvastatin within cholesterol lowering medications.
For me, the case for telmisartan is way clearer and stronger than for atorvastatin.
But yeah, the hypertension guidelines really rarely recommend specific drugs and mostly deal with class (although if you read the whole document, they might address some intra-class differences). Here are the latest European guidelines; other countries are almost identical (in terms of overall strategy and choice of classes):
I meant as a drug-specific recommendation for hypertension as atorvastatin is for primary prevention of heart disease. I see so it’s up to us to figure out the best drug within each class.
Exactly. Still, most guidelines (and I think everyone) agree that long-acting agents should be preferred to maintain BP control over a long period of time and decrease BP variability as much as possible. The longest acting ACEi is ramipril, ARB is telmisartan, CCB is amlodipine, and thiazide/thiazide-like is chlorthalidone (or maybe indapamide SR?). For beta blockers I think it’s nadolol. Then for dementia prevention (and potentially longevity?) the best seems to be ARB (over ACEi), DHP CCB (over non DHP CCB), and thiazide (over non thiazide diuretic and beta blockers). Which gives us telmisartan + amlodipine + indapamide SR (chlorthalidone did not outperform HCTZ in a recent trial).
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This is so incredibly helpful. You have convinced me to switch from Nebivolol to Indapamide 1.5 SR to go along with my 40mg Telmisartan. My diastolic sometimes goes below 60 which I don’t like. Just want to keep the systolic controlled.
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Check potential counter indications (if any, I don’t know) before switching.
Yup, Beta blocker is a rev limiter
By the way @LVareilles some researchers consider that DBP can go as low as 60: New research could change how doctors treat some patients with high blood pressure
I don’t know much about that.
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Mine hovers between 54 and 67 depending on when I measure it. Some instances I’ve even seen lower.
Do I need to watch out for my sodium levels going too low on Indapamide?
Wow that’s very low indeed.
Yes indapamide affects electrolyte levels (also uric acid) so do a blood test before / after maybe. And talk to a doctor who has experience prescribing it.
Ah yes, my uric acid runs low at around 3.8 so glad you said something. I’ll look more into it.
Indapamide increases uric acid, so it should be fine for you: “At daily doses of 2.5 mg and 5 mg a mean decrease of serum potassium of 0.5 and 0.6 mEq/Liter, respectively, was observed and uric acid increased by about 1 mg/100 mL.” (source)
Please note that indapamide 1.5 mg SR is more neutral in terms of impact on electrolytes and uric acid compared to normal release 2.5 mg and 5 mg:
- “Serum uric acid level was slightly increased after short-term therapy, but was restored to baseline values during long-term therapy with indapamide SR 1.5 mg/day.” (Metabolic Profile of Indapamide Sustained-Release in Patients with Hypertension 2013)
- “The indapamide sustained release 1.5 mg dose was also associated with smaller increases in uric acid than the immediate release 2.5 mg dosage (34 versus 51 μmol/l)” (Redefining diuretics use in hypertension: why select a thiazide-like diuretic? 2019)
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Perfect. This just might be the right drug for me then. Thank you for posting that.
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Please let us know how it goes!
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I liked this article, but I need to spend another 100 hours actually understanding all of it. I thought it’d fit in well w/ the forum.
Angiotensin II blockade: a strategy to slow ageing by protecting mitochondria?
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This paper is old. Most recent papers suggest that you should stimulate (and not inhibit) type 2 and 4 angiotensin II receptors. Drugs that do that are ARBs (as opposed to ACEIs), DHP CCBs (as opposed to non DHP CCB) and thiazide/thiazide-like diuretics (as opposed to beta blockers): Type 2 and 4 Angiotensin II Receptor Antihypertensives and Dementia