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Out of Hours

The chronotherapy of hypertension: or the benefit of taking blood pressure tablets at bedtime

Gervase Vernon
British Journal of General Practice 2017; 67 (657): 171. DOI: https://doi.org/10.3399/bjgp17X690269
Gervase Vernon
John Tasker House Surgery, Dunmow, Essex.
Roles: GP
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The chronotherapy of hypertension is a relatively new practice in the UK. Yet the latest RCT (MAPEC)1 shows that taking blood pressure (BP) tablets at bedtime instead of in the morning (for those of our patients who are on more than one BP tablet per day) lowers the night-time blood pressure and reduces the relative risk of major cardiovascular disease (CVD) events by about 60% (P = 0.33) over 5 years.2

This translates (very roughly) into a number needed to treat (NNT) of 300 to prevent one major cardiovascular event per year. This is comparable to the NNT for primary prevention with statins. In a practice of 10 000 patients, based on the figures in our practice, this would translate into about four fewer major cardiovascular events per year, a clinically significant benefit.

WHAT IS THE EVIDENCE?

The idea is not that new, but was suggested by Bartter over 35 years ago.3 There have been three positive trials of night-time antihypertensives: HOPE (ramipril),4 Syst-Eur5 (nifedipine), and MAPEC1 (which was a Spanish RCT of 2000 patients randomised to morning or night-time tablets over 5 years). Of note, the intervention, according to the MAPEC authors, appears to be particularly appropriate in diabetics,6 those with chronic kidney disease (CKD),7 those with nocturnal hypertension, but not those with obstructive sleep apnoea (OSA).8

There is clearly scope to repeat a trial similar to MAPEC in a UK general practice population. These trials also raise questions about the use and funding of 24-hour ambulatory BP monitoring not just for diagnosis, but also for monitoring. This is because the best results in terms of preventing major cardiovascular events occurred in those whose night-time BP was controlled to goal (<120/70).9 Clearly one should not neglect daytime blood pressure targets of less than 150/90 for patients with essential hypertension aged ≥60 years, as recommended by current guidelines,10,11 although these targets are often difficult to reach.

To those who might ask, ‘Why have we not heard of these results?’, the answer is straightforward. This intervention has no cost; therefore there is no budget to publicise it. In the case of statins, the pharmaceutical industry, standing to profit from them, had a large marketing budget. However, a no-cost intervention is particularly suited to today’s NHS budget.

This is an evidence-based intervention suitable for individual GPs and for clinical commissioning groups (CCGs). Changing patients to bedtime BP tablets should, however, be tailored to the individual, because, if patients fail to take their BP tablets as a result of the intervention (reduced concordance/compliance), harm rather than benefit will result.

  • © British Journal of General Practice 2017

REFERENCES

  1. 1.↵
    1. Hermida R,
    2. Ayala D,
    3. Mojón A,
    4. Fernández JR
    (2010) Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int 27(8):1629–1651.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Smolensky MH,
    2. Hermida RC,
    3. Ayala DE,
    4. Portaluppi F
    (2015) Bedtime hypertension chronotherapy: concepts and patient outcomes. Curr Pharm Des 21(6):773–790.
    OpenUrl
  3. 3.↵
    1. Bartter FC,
    2. Delea CS,
    3. Baker W,
    4. et al.
    (1976) Chronobiology in the diagnosis and treatment of mesor-hypertension. Chronobiologia 3(3):199–213.
    OpenUrlPubMed
  4. 4.↵
    1. Sleight P
    (2000) The HOPE Study (Heart Outcomes Prevention Evaluation). J Renin Angiotensin Aldosterone Syst 1(1):18–20.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Staessen J,
    2. Fagard R,
    3. Thijs L,
    4. et al.
    (1997) Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 350(9080):757–764.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Hermida RC,
    2. Ayala DE,
    3. Mojón A,
    4. Fernández JR
    (2011) Influence of time of day of blood pressure–lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care 34(6):1270–1276.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Hermida RC,
    2. Ayala DE,
    3. Mojón A,
    4. Fernández JR
    (2011) Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol 22(12):2313–2321.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Serinel Y,
    2. Yee BJ,
    3. Grunstein RR,
    4. et al.
    (Dec 14, 2016) Chronotherapy for hypertension in obstructive sleep apnoea (CHOSA): a randomised, double-blind, placebo-controlled crossover trial. Thorax, pii: thoraxjnl-2016-209504.
  9. 9.↵
    1. Orías M,
    2. Correa-Rotter R
    (2011) Chronotherapy in hypertension: a pill at night makes things right? J Am Soc Nephrol 22(12):2152–2155.
    OpenUrlFREE Full Text
  10. 10.↵
    1. James PA,
    2. Oparil S,
    3. Carter BL,
    4. et al.
    (2014) 2014 evidence-based guideline for the management of high blood pressure in adults report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311(5):507–520.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Qaseem A,
    2. Wilt TJ,
    3. Rich R,
    4. et al.
    (Jan, 2017) Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med, 17, doi:10.7326/M16-1785.
    OpenUrlCrossRef
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British Journal of General Practice: 67 (657)
British Journal of General Practice
Vol. 67, Issue 657
April 2017
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The chronotherapy of hypertension: or the benefit of taking blood pressure tablets at bedtime
Gervase Vernon
British Journal of General Practice 2017; 67 (657): 171. DOI: 10.3399/bjgp17X690269

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The chronotherapy of hypertension: or the benefit of taking blood pressure tablets at bedtime
Gervase Vernon
British Journal of General Practice 2017; 67 (657): 171. DOI: 10.3399/bjgp17X690269
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