How long should treatments be continued?
BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c4102 (Published 19 August 2010) Cite this as: BMJ 2010;341:c4102
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
The editorial by Craig and colleagues summarise some very relevant
questions regarding when a treatment should be discontinued [1]. It is all
too often that a hospital doctor sees patients coming to hospital on one,
two or three antihypertensives for their 'good control' of blood pressure.
Some of these patients also present with low blood pressure secondary to
dehydration, blood loss, cardiac dysfunction and infection-related
vasodilatation. The antihypertensives are appropriately stopped and very
often on discharge, these medications are not recommenced on their take-
home prescriptions. Does this have a negative impact on the long-term
outcome for these patients?
The success of withdrawal of antihypertensives has been studied
mainly in general practice. A longitudinal observational study in 18
general practices reported by Aylett et al showed one-fifth of well-
controlled hypertensives in British primary health care could have their
medication withdrawn without the relapse of their hypertension or any
negative consequences [2]. Also those who relapse, they are more likely to
do so in the first three months. An American publication reviewed eighteen
studies of antihypertensive medication withdrawal and reported average
success rates of 40% after 1 year of follow-up and 27% after 2 years were
achieved [3]. This was also extendable to older individuals with an
average success rate of over 25%. The TONE (Trial of Nonpharmacologic
Interventions in the Elderly) Cooperative Research Group studied the
predictors of successful antihypertensive withdrawal include patients with
well-controlled hypertension with a recent diagnosis and treatment, and
who adhere to life-style interventions involving weight loss and sodium
reduction [4]. Predictors of normotension on withdrawal of
antihypertensive drugs in elderly patients are being between 65-74 years,
lower "on-treatment" systolic blood pressure, monotherapy, and
interestingly patients with a greater waist:hip ratio [5].
It would be worthwhile assessing the outcomes of similar
interventions on new hypertensive patients who are commenced on treatment
in the hospital, or required additional medications for blood pressure
control during hospital stay. The negative and positive impact of
discontinuation of antihypertensive for various reasons whilst in the
hospital also requires examination with long term follow-up. These
analyses should provide answers to the hospital physicians to the not so
uncommonly asked question can I stop my blood pressure tablets?
References
1.Craig JC, Webster AC, Loy C. How long should treatments be
continued? BMJ. 2010 Aug 19;341:c4102.
2.Aylett M, Creighton P, Jachuck S, Newrick D, Evans A. Stopping drug
treatment of hypertension: experience in 18 British general practices. Br
J Gen Pract. 1999; 49: 977-80.
3.Froom J, Trilling JS, Yeh SS, Gomolin IH, Filkin AM, Grimson
RC.Withdrawal of antihypertensive medications. J Am Board Fam Pract.
1997; 10: 249-58.
4.Espeland MA, Whelton PK, Kostis JB, Bahnson JL, Ettinger WH, Cutler
JA, Appel LJ, Kumanyika S, Farmer D, Elam J, Wilson AC, Applegate
WB.Predictors and mediators of successful long-term withdrawal from
antihypertensive medications. TONE Cooperative Research Group. Trial of
Nonpharmacologic Interventions in the Elderly. Arch Fam Med. 1999; 8: 228-
36.
5.Nelson MR, Reid CM, Krum H, Muir T, Ryan P, McNeil JJ. Predictors
of normotension on withdrawal of antihypertensive drugs in elderly
patients: prospective study in second Australian national blood pressure
study cohort. BMJ. 2002; 325: 815.
Competing interests: No competing interests
Three questions for prescribers
Craig, Webster, and Loy suggest three questions to answer before introducing a therapeutic intervention:
- Does it do more good than harm?
- How intense should treatment be?
- For how long should it be given?
The first question illustrates a difficulty with evidence-based medicine - that it is generally based on the results of studies in populations, which are not always relevant to individual patients, particularly since some harms may be more acceptable to some patients than to others, and individual susceptibility factors alter the chance of benefit and the risks of harms [1].
Furthermore, the answer to the first question depends in part on the answers to the second and third questions. For example, prolonged treatment with low-dose prednisolone has a less favourable benefit to harm balance than a short high-dose course, and folinic acid rescue is needed after high doses of methotrexate but not low doses.
In addition, the second and third questions are only two aspects of how to proceed after a positive answer to the first question. For example, important questions to ask when a pharmacological intervention is planned include how to start therapy (e.g. with a test dose, a low dose, or a loading dose), how to change the dose in order to optimize the benefit to harm balance, the appropriate route of administration and formulation, and the frequency and duration of administration. Comparable questions for other types of intervention (e.g. surgical) can be formulated.
Thus, the three questions posed by Craig, Webster, and Loy could be replaced by two:
- Is the benefit to harm balance likely to be favourable in this case [i.e. in this patient and for a given treatment regimen]?
- If so, what is the appropriate regimen?
To these, one should add a third question: "How should therapy be monitored?" Although this is closely linked to the second question, it is worth asking separately, since it is often badly done [2] or not at all [3].
For a more detailed set of principles see the British Pharmacological Society's "Ten Principles of Good Prescribing" [4].
References
1. Aronson JK, Ferner RE. Joining the DoTS. New approach to classifying adverse drug reactions. BMJ 2003; 327: 1222-5.
2. Glasziou P, Irwig L, Aronson JK, editors. Evidence-based Medical Monitoring: From Principles to Practice. Oxford: Wiley-Blackwell, 2008.
3. Coleman JJ, McDowell SE, Evans SJ, Gill PS, Ferner RE. Oversight: a retrospective study of biochemical monitoring in patients beginning antihypertensive drug treatment in primary care. Br J Clin Pharmacol. 2010l; 70: 109-17.
4. British Pharmacological Society. Ten Principles of Good Prescribing. http://www.bps.ac.uk/uploadedfiles/PMeBulletinUploads/
BPSPrescribingStatement03Feb2010.pdf (last accessed 1 September 2010).
Competing interests: No competing interests