Intended for healthcare professionals

Rapid response to:

Practice Guidelines

Hypertension in adults: summary of updated NICE guidance

BMJ 2019; 367 doi: (Published 21 October 2019) Cite this as: BMJ 2019;367:l5310

Rapid Response:

Re: Hypertension in adults: summary of updated NICE guidance

Martin Kittel has made important comments in his rapid response to the publication of new NICE guidelines on hypertension in adults (Nov 2). He points out that the new guidelines omit any comment on the time of day of administration of medication for hypertension, despite the publication from the Hygia trial this year by Hermida and colleagues (1) which provides strong evidence from a well conducted trial, with a mean follow up period of 6.4 years, that evening administration results in better outcomes. In 2017 a meta-analysis by Wang and colleagues (2) had reviewed 25229 studies of hypertension management, concluding that evening dosing contrasted with morning, was more effective and did restore ‘dipping’ and decrease urinary albumin in those few studies that made that comparison.

The new guidelines support the use of ambulatory blood pressure monitoring (AMBP) and favour this over domiciliary self-measurement, but without comment on the merits of considering “dipping” of nocturnal blood pressure when deciding on when to start treatment or in evaluating the response to treatment or to detect those patients that may need management of sleep apnoea before blood pressure can be controlled. The combined use of both methods is useful in clinical practice, The guidelines do advise measuring renal function but have not provided guidelines on those “with chronic renal disease” with hypertension. They do not comment on the importance of repeat renal function measurements to establish if there may be progressive renal dysfunction which, if present, make control of blood pressure, including of nocturnal hypertension, even more important.

In 1961, with colleagues in Bristol, we reported on the first automated device for BP measurement over 24 hours and established that BP did not fall during sleep in patients with “malignant” hypertension, but “dipped” in “essential” hypertension (2). We postulated that no nocturnal dip contributed to progression into malignant hypertension with its association with rapid progression into renal failure (CRF). In more recent publications (4,5) I have advocated n-of-1 analysis of data from individual patients, to establish in cross-over studies of time of administration, in both trials and in clinical practise, if progression to end-stage renal failure has been influenced by timing of therapy. In the clinic changes in the time of medication, eg from morning to bedtime, can be evaluated by graphical presentations, or/and with results of N-of-1 statistical analysis, to demonstrate change points in blood pressure control and in renal failure progression. The method used by me when in clinical practise demonstrated statistically significant changes in progression, with alteration in administration time, slowing or arresting progression in individuals (5). I suggest that guidelines should encourage trend analysis in real time in clinical practise to define statistically favourable change points associated with time of administration in individuals, especially in those progressing to end-stage kidney failure, and the use of n-of-1 analysis as an indication to review management when progression towards renal failure needing dialysis is not arrested.

• 1 Hermida RC et al. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. European Heart Journal (2019) 0, 1–12

• 2 Wang C, Ye Y, Liu C, Zhou Y, Lv L, Cheng C et al. Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis. Intern Med J 2017; 47: 900–6.

• 3 Shaw DB, Knapp MS, Davies DH. Variations in the blood pressure of hypertensives during sleep. Lancet 1963; 281: 797–9.

• 4 Knapp MS, Smith AFM, Trimble IM, Pownall R, Gordon K. Mathematical and statistical aids to evaluate data from renal patients. Kidney Int 1983; 24: 474–86.

• 5 Knapp MS. A transverse and longitudinal audit of pre-dialysis renal failure in a non-metropolitan clinic. Nephrology2003; 8(Suppl): A90.

Competing interests: No competing interests

19 November 2019
martin s knapp
physician (retired)
previously Universities of Melbourne, Nottingham, Bristol
Ivanhoe, Vic.,3079, Australia