Blood pressure control – take the low road

Take the low road

Parts I and II of this series explain why this is important and how to recognize hypertension. This post is about how to get it all under control.

Your target and how to bullseye it

We need ‘normal’ [young person] levels of <120/<80 to minimise cardiovascular risk. For example, a level of 110/70 would be wonderful.

Two Key Questions:

1. How do we get to that level when our BP is up?
2. Is this degree of reduction safely achievable?

There are lifestyle and medical approaches.

The best approach is a combined one. Don’t say ”I will try the lifestyle approach first and see about medication if that fails”, because any time spent with high BP is damaging, and the acute events like heart attack and stroke that may occur with untreated BP are life threatening. SO do not delay getting your BP down. Fortunately, as modern BP medication is non-harmful there is no reason to be shy of taking treatment. 

The optimum approach is start on medication, get control, do the lifestyle change, too, and maybe later, reduce the meds a bit. Moreover, if you are overweight, a drinker, eat a lot of salt, and have insulin resistance you will only get optimum control by making lifestyle changes to alter those factors alongside your medication. Around 50% of you will need only one drug to get your BP down but equally 50% will need two.

Salt reduction is always helpful but has a low impact; magnesium supplementation at around 300mg daily has a significant effect.

The Short Answer

Reduce alcohol; lose 5-10 Kg depending on how over-heavy you are; try for 10,000 steps a day and a more active life overall; take either candesartan 8mg [potentially increasing to 16mg] or indapamide Slow Release 1.5 mg as your first line agent and add the other drug if you need a combination to get the needed result. It is possible that taking a magnesium supplement as I recommend for all over 60’s may have a beneficial effect.

To get the whole inside story read more

The evidence – you betta believe it!

In the SPRINT study, participants moving systolic below BP 120 mmHg gained a 25% reduction in cardiovascular mortality after one year, when compared to a systolic treatment target of 140 mmHg [1]. Likewise, the 2021 STEP (“Chinese SPRINT”) study found that lowering systolic BP to <130 mmHg rather than <150 mmHg reduced composite cardiovascular outcomes by 26% [2]. This high quality study data has revolutionized medical guidelines which now recommend taking a more aggressive treatment approach.

Too much of a good thing - can you overtreat?

Twenty years ago trying to get to these treatment targets would have incurred significant side effects from the drugs then in use. Today a combined approach including a clear commitment to modify lifestyle will not cause problems. Using combination therapies allows your physician to use different BP lowering mechanisms to increase effectiveness whilst limiting dose related side effects.

A single agent may do it for YOU, but combo’s get maximum change with least problems.

Real life scenarios.

Although it is possible to reduce BP to the target level some may find the lifestyle changes challenging and with ‘resistant’ hypertension medication may only partially succeed. Hypertension is a multifactorial condition and the choice of drugs used can be critical. If you are having trouble get a specialist involved. If weight is a problem consider a GLP-1 agonist like Wegovy or Mounjaro. If you only get to 130/90 it is way better than 150/100.

Which treatment should you get?

I give very specific information here so you can discuss treatment options with your doctor. The options appear complex at first sight because treatment may involve 5 classes of drugs. The technical bit – the method of action and class – you can skip this if you aren’t into the fine detail.

The 5 classes (including abbreviations and examples) are  

1. ARB (Angiotensin II receptor Blockers). Examples: Candesartan, Losartan
2. ACEi (Angiotensin Converting Enzyme inhibitors). Examples: Lisinopril, ramopril [“x-pril”]
3. DhpCCB  (DiHydroPyridine Calcium Channel Blockers). Examples: Amlodipine, nifedipine [“x-pine”]
4. Non-DhpCCB (Non-DiHydroPyridine Calcium Channel Blockers). Examples: Verapamil, Diltiazem
5. ThZ (Thiazide/ thiazide-like diuretics). Examples: Hydrochlorthiazide, Bendrofluazide, Chlorthalidone, Indapamide

By the way your treatment should NOT be a beta blocker - expert guidelines no longer advise this except as management of a more complex situation where there is heart failure.

Frequently Asked Questions - and the key things you need to consider

1. Who should be treating you? When your BP is diagnosed, initial treatment is usually from a family doctor. If single or two drug treatment succeeds and you have no problems with the medication, then that is ideal. If you already have some heart or kidney issues, then a management by a specialist may be more appropriate to take your cardiac issue into account in choice of drugs used. This also follows if the initial treatment doesn’t work out.

2. What starting point? A first line option from the list below – then when that is established and the effect is seen, a second drug may be used to improve control if needed. I advise against starting with a combination. If problems occur on a starting combination, it is difficult to know which drug is causing it. Secondly, if there are problems with your first line then using an alternative single agent is appropriate.

3. Does it matter what the first line drug is? In terms of efficacy a comprehensive study suggests no, except for specific situations [see below]. The first line probably should be one with low side effects. A comparison of ACEi’s and ARBS showed no difference in major outcomes like stroke and heart attack or heart failure but … ARBs had fewer side effects and therefore would be a good choice [3]. Similarly the thiazide-like drug indapamide is the most effective of that class and is very well tolerated by all, so would be an equal candidate for your first line. My preference would therefore be for Candesartan or Indapamide, as first choices.  [World-wide the CCB, amlodipine, is often used as the first agent. There is a risk of side effects with higher doses. If you get good control with no side effects, then that is a perfectly OK choice].

4. What are the special situations that affect starting drug choice? Some opinion suggests that Blacks respond better to CCBs than other first line options [4 , 5]. ThZs help in BP where there is salt retention and blood volume expansion but are less good for diabetics or those with gout as they may raise blood sugar and uric acid. If you have any pre-existing heart or kidney problems, then ACEi’s and the two types of CCB may be appropriate choices. My conclusion is that unless a cardiologist or nephrologist advises an ACEi or CCB then starting with an ARB or indapamide is going to achieve an equal BP lowering effect and more patient compliance [it is easier to stick to the medication]. The very special situations are below  

• Patients with heart failure with reduced ejection fraction should be treated initially with a beta blocker and an ACEi or ARB (or an angiotensin receptor–neprilysin inhibitor), followed by add-on therapy with a mineralocorticoid receptor antagonist and a diuretic based on volume status.
• Treatment for patients with chronic kidney disease and proteinuria should include an ACEi or ARB plus a thiazide diuretic or a calcium channel blocker. 
• Patients with diabetes mellitus should be treated similarly to those without diabetes unless proteinuria is present, in which case combination therapy should include an ACEi or ARB [6].

5. What are the best drugs in each class? 

• The thiazide-like diuretics indapamide and chlorthalidone are more effective than hydrochlorothiazide [HCTZ] [which I would not accept]. Chlorthalidone reduces systolic blood pressure (BP) better than HCTZ at equivalent doses with similar effects on potassium levels [7]. Indapamide comes out best of all when the three are compared head to head and has both a longer duration of action [it lowers BP overnight as well as daytime]. It reduces cardiovascular events, as well [8]. The slow release formulation [Indapamide SR] is as effective with a lower dose and a more even blood level profile [9]. 
• ARBs. Candesartan is more effective than Losartan both singly and in combination with other drugs like indapamide because it lowers the peak and trough pressures more, has a more sustained effect and covers the loss of control that may occur through missed tablets [10].
• ACEi’s.  There is no data to support one over another. Ramipril is used for those with kidney disease and Lisinopril is the most frequent other prescription.
• DPH CCB. Amlodipine is the most effective [11].
• Non DPHCCB. Diltiazem comes out best [10].

6. Possible combinations (first line drug, second line drug for each class)  

• ARB/ ThZ:  1st line: Candesartan, 2nd line: Indapamide SR
• ThZ / ARB: 1st line: Indapamide, 2nd line:  SR Candesartan
• ACEi/ ThZ: 1st line: Ramipril/ Lisinopril, 2nd line:  Indapamide
• DHPCCB/ThZ: 1st line: Amlodipine, 2nd line:  Indapamide
• Non DHPCCB/ThZ: 1st line: Diltiazem, 2nd line:  Indapamide
• DHP/ nonDHPCCB: 1st line: Amlodipine, 2nd line: Diltiazem

Conclusion

Be proactive and energetic in dealing with your BP – it may save your life. There are plenty of options, one of these will work for you. 

Sources

[1] SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2Roush GC, Ernst ME, Kostis JB, Tandon S, Sica DA. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension. 2015 May;65(5):1041-6. doi: 10.1161/HYPERTENSIONAHA.114.05021. Epub 2015 Mar 2. PMID: 25733245.103-2116

[2] Zhang W, Zhang S, Deng Y, et al. Trial of intensive blood-pressure control in older patients with hypertension. N Engl J Med. 2021;385(14):1268-1279.

[3] Chen R, Suchard MA, Krumholz HM, Schuemie MJ, Shea S, Duke J, Pratt N, Reich CG, Madigan D, You SC, Ryan PB, Hripcsak G. Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study. Hypertension. 2021 Sep;78(3):591-603. doi: 10.1161/HYPERTENSIONAHA.120.16667. Epub 2021 Jul 26. PMID: 34304580; PMCID: PMC8363588.

[4] Suchard MA, Schuemie MJ, Krumholz HM, et al. Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis. Lancet. 2019;394(10211):1816-1826.

[5] Gardner NJ. Treating hypertension in Black patients. JAAPA. 2022;35(2):15-18

[6] Smith DK, Lennon RP, Carlsgaard PB. Managing Hypertension Using Combination Therapy. Am Fam Physician. 2020 Mar 15;101(6):341-349. PMID: 32163253.

[7] Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JJG, Phillips BB, Zimmerman MB, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006;47(3):352–8. doi: 10.1161/01.HYP.0000203309.07140.d3.

[8] Cardiovascular Protective Properties of Indapamide. Bruce Campbell, D. et al. American Journal of Cardiology, Volume 65, Issue 17, H11 - H27.

[9] Robinson DM, Wellington K. Indapamide sustained release: a review of its use in the treatment of hypertension. Drugs. 2006;66(2):257-71. doi: 10.2165/00003495-200666020-00011. PMID: 16451099.

[10] Bakris G, Gradman A, Reif M, Wofford M, Munger M, Harris S, Vendetti J, Michelson EL, Wang R; CLAIM Study Investigators. Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study. J Clin Hypertens (Greenwich). 2001 Jan-Feb;3(1):16-21. doi: 10.1111/j.1524-6175.2001.00826.x. PMID: 11416677; PMCID: PMC8101876.

[11] Basile J. The role of existing and newer calcium channel blockers in the treatment of hypertension. J Clin Hypertens (Greenwich). 2004 Nov;6(11):621-29; quiz 630-1. doi: 10.1111/j.1524-6175.2004.03683.x. PMID: 15538095; PMCID: PMC8109670.