Using thresholds based on risk of cardiovascular disease to target treatment for hypertension: modelling events averted and number treatedBMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7236.680 (Published 11 March 2000) Cite this as: BMJ 2000;320:680
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In a recent article by Baker et al.  the impact of using
thresholds based on absolute risk of cardiovascular disease to target drug
treatment of hypertension on the number of people treated and the number
of disease events averted over 5 years was predicted. We recognize the
relevance of this analysis and would like to emphasize the importance of
investigating the likely impact of treatment recommendations on patients
The impact of treatment of hypertension on the number of
cardiovascular disease events averted in the population was predicted on
the basis of Framingham risk equations and results from randomised
controlled trials (RCTs). Although the Framingham risk equations have been validated in several
populations, the use of real follow-up data to estimate the actual
absolute risk of cardiovascular disease would have been more accurate.
Moreover, the actual benefit of treatment of hypertension in the reduction
of the incidence of cardiovascular diseases under circumstances of daily
medical practice is unknown. RCTs provide evidence of what can be achieved
with drug treatment of hypertension in the most favourable circumstances
(efficacy), because RCTs usually exclude certain categories of patients
and are mostly conducted under strict, protocol-driven conditions .
Therefore, the generalizability of findings from RCTs to the general
population is limited and emphasizes the need for assessments of the
effect of drug treatment of hypertension in daily medical practice
(effectiveness). The results from several observational studies suggest a
less beneficial effect than achieved in RCTs, or even a harmful effect of
pharmacological treatment of hypertension in daily medical practice .
Therefore, extrapolation of results from RCTs to daily medical practice
may not be valid. However, these observational studies were probably
biased because of confounding by indication .
Recently, we used the Dutch guidelines on the management of
hypertension to create a prognostically similar untreated reference group
to which treated hypertensive patients were compared . In this
prospective population-based cohort study we estimated that drug treatment
of hypertension was associated with a 39% reduced risk of stroke and that
about 46 hypertensive patients need to be treated pharmacologically for 5
years to prevent one stroke in the general Dutch population .
findings support extrapolation of results from RCTs to daily medical
practice. Similar analyses should be undertaken to estimate the effect of
drug treatment of hypertension on the incidence of other cardiovascular
disease events in order to justify extrapolations from RCTs. We realize
that extrapolations of results from RCTs to daily medical practice are the
only alternative in the absence of valid estimates of the effectiveness of
drug treatment of hypertension in daily medical practice. However, we
suggest that valid assessments of the effect of treatment of hypertension
in daily medical practice should complement predictions of the effect of
drug treatment of hypertension based on RCTs.
1. Baker S, Priest P, Jackson R. Using thresholds based on risk of
cardiovascular disease to target treatment for hypertension: modelling
events averted and number treated. BMJ 2000;320:680-5.
2. Messerli FH, Grodzicki T. Antihypertensive therapy in the elderly:
Evidence-based guidelines and reality. Arch Intern Med 1999;159:1621-2.
3. Grobbee DE, Hoes AW. Confounding and indication for treatment in
evaluation of drug treatment of hypertension. BMJ 1997;315:1151-4.
4. Klungel OH, Stricker BHC, Paes AHP, Seidell JC, Bakker A, Voko Z,
Breteler MMB, de Boer A. Excess stroke among hypertensive men and women
attributable to undertreatment of hypertension. Stroke 1999;30:1312-8.
5. Klungel OH, Stricker BHC, Breteler MMB, Seidell JC, Psaty BM, de
Boer A. Effectiveness of pharmacological treatment of hypertension under
everyday circumstances with regard to the reduction of stroke incidence.
Value in Health 1999;5:355-6 [abstract].
Olaf H. Klungel, PharmD, PhD,
Assistant Professor of Pharmacotherapy.
Hubert G.M. Leufkens, PharmD, PhD,
Professor of Pharmacoepidemiology.
Anthonius de Boer, MD, PhD,
Associate Professor of Pharmacotherapy.
From the department of Pharmacoepidemiology and Pharmacotherapy,
Utrecht Institute of Pharmaceutical Sciences, Utrecht University, the
Correspondence to O.H. Klungel, department of Pharmacoepidemiology
and Pharmacotherapy, Utrecht Institute of Pharmaceutical Sciences, Utrecht
University, Sorbonnelaan 16, 3584 CA Utrecht, the Netherlands
Competing interests: No competing interests