Beta-Blockers in Hypertension
Adding Insult to Injury*
Norman M. Kaplan, MD
Beta-blockers have been found not to be effective for
primary prevention of cardiovascular disease in patients with
primary hypertension. The problem was first recognized by
Messerli et al. (1) in 1998. They pointed out the signifi-
cantly lesser benefit of beta-blocker therapy in 2 trials versus
diuretic-based therapy in 7 separate trials. Their presenta-
tion could not have been clearer: “Diuretic therapy was
superior to blockade with regard to all end points. . .
?-blocker therapy only reduced the odds for cerebrovascular
events but was ineffective for preventing coronary heart
disease, cardiovascular mortality and all-cause mortality.”
See page 1482
This clear distinction was not referenced in the 2003 Joint
National Committee (JNC) report (2), which favored a
diuretic for first drug but indicated that beta-blockers were
suitable alternatives, particularly when a “compelling” indi-
cation was present, including heart failure, post-myocardial
infarction, high coronary disease risk, or diabetes mellitus.
A few months after the 2003 JNC report was published,
Messerli et al. (3), with 3 well-established hypertension ex-
perts, said it again, even more clearly: “The time has come to
admit that beta-blockers should no longer be considered appro-
priate for first-line therapy of uncomplicated hypertension.”
The British and European Hedges
Even after this indictment, however, the 2004 British
Hypertension Society (BHS) guidelines (4) put beta-
blockers alongside angiotensin-converting enzyme inhibi-
tors (ACEIs) and angiotensin II receptor blockers (ARBs)
as initial therapy for hypertensive patients under age 55
years and for nonblack patients. The 2004 BHS guidelines
did, however, hedge their position, stating that according to
their AB/CD algorithm, either an ACEI or an ARB (A) or
a beta-blocker (B) should be chosen for younger and
nonblack patients whereas either a calcium-channel blocker
(C) or a diuretic (D) should be chosen for patients who are
over age 55 years or black, but the algorithm does place the
“B” in brackets. The report says, “the reason is to emphasize
the fact that recent trials have reported an increase in onset
of diabetes in patients treated with B or D drugs compared
with A or C drugs, especially when B and D are combined.
We advise caution when using B?D in patients at especially
high risk of developing diabetes as for example, patients
with a strong family history of type 2 diabetes, obesity,
impaired glucose tolerance, features of metabolic syndrome
or of South Asian and African-Caribbean descent” (4).
Note that the warning did not relate to the lesser benefit
of beta-blockers in general, only to their propensity to bring
The British did amend their position in a statement on
their website on June 28, 2006, providing a new algorithm
without a B (beta-blocker) anywhere to be found and
including the statement that “beta-blockers are no longer
preferred as a routine initial therapy for hypertension” (5).
This good advice, however, did not get through to the
writers of the 2007 European Society of Hypertension and
European Society of Cardiology guidelines (6). They stated:
“Beta-blockers may still be considered an option for initial
and subsequent antihypertensive treatment strategies. Be-
cause they favor an increase in weight, have adverse effects
on lipid metabolism and increase (compared with other
drugs) the incidence of new-onset diabetes, they should not
be preferred, however, in hypertensives with multiple met-
abolic risk factors including the metabolic syndrome. . .” (6).
The Swedish Explosion
Messerli et al. (7) said it again in 2007, in this Journal,
adding a litany of side effects from beta-blockers, including:
1) precipitation of diabetes; 2) little effect on regression of
left ventricular hypertrophy; 3) likely failure to improve
endothelial function; 4) weight gain; and 5) decrease in
To emphasize their position, they added: “For every
myocardial infarction or stroke prevented in the Medical
Research Council study (8), 3 patients treated with atenolol
withdrew from the study secondary to impotence and
another 7 withdrew because of fatigue” (7).
Despite the persistence of Messerli et al. (1), the beta-
blocker atenolol was the fourth most prescribed drug in the
U.S. in 2005, with 44 million prescriptions per year (7). It
required 2 papers in the Lancet from 3 Swedish authors
(9,10), with their accompanying editorials, to bring the issue
to the currently almost unanimous agreement that beta-
blockers are no longer an appropriate choice for initial or, as
stated in the 2006 BHS addendum, subsequent therapy of
uncomplicated hypertension. In retrospect, it took the
exhortation of Messerli et al. (1) to set the stage but, perhaps
with Americans being generally less accepted in the rest of
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the University of Texas Southwestern Medical Center, Hypertension
Division, Dallas, Texas.
Journal of the American College of Cardiology
© 2008 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 52, No. 18, 2008
the world these days, it took the Swedes to lower the
Rather surprisingly, in view of the prior analyses by
Messerli et al. (1) showing equal protection against stroke by
beta-blockers, the problem shown by the Swedish meta-
analyses was lesser protection against strokes by beta-
The Additional Blow
The paper by Bangalore et al. (11) in this issue of the Journal
adds another post-mortem explanation for the fall of beta-
blockers, showing higher mortality associated with the
slower heart rate they induce. Of interest, the fall in pulse
rate is an obvious mechanism for the higher central blood
pressure with beta-blocker–based therapy noted by Williams
et al. (12) in the CAFE (Conduit Artery Function Evaluation)
study. With this addition to the evidence, beta-blockers will
surely remain as indicated for heart failure, for after myocardial
infarction, and for tachyarrhythmias, but no longer for hyper-
tension in the absence of these compelling indications.
Reprint requests and correspondence: Dr. Norman M. Kaplan,
University of Texas Southwestern Medical Center, Hypertension
Division, 5323 Harry Hines Boulevard, Dallas, Texas 75390.
1. Messerli F, Grossman E, Goldbourt U. Are beta-blockers efficacious
as first-line therapy for hypertension in the elderly? A systematic
review. JAMA 1998;279:1903–7.
2. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the
Joint National Committee on prevention, detection, evaluation, and
treatment of high blood pressure: the 2003 JNC report. JAMA
3. Messerli FH, Beevers DG, Franklin SS, Pickering TG. Beta-blockers
in hypertension—the emperor has no clothes: an open letter to present
and prospective drafters of new guidelines for the treatment of
hypertension. Am J Hypertens 2003;16:870–3.
4. Williams B, Poulter NR, Brown MJ, et al. British Hypertension
Society guidelines for hypertension management 2004 (BHS-IV):
summary. BMJ 2004;328:634–40.
5. The National Collaborating Centre for Chronic Conditions. Hyperten-
sion. Management in adults in primary care: pharmacological update.
Available at: http://www.nice.org.uk/nicemedia/HypertensionGuide.pdf.
Accessed July 15, 2008.
6. Mancia G, De Backer G, Dominiczak A, et al. 2007 guidelines for the
management of arterial hypertension: the Task Force for the Manage-
ment of Arterial Hypertension of the European Society of Hyperten-
sion (ESH) and of the European Society of Cardiology (ESC).
J Hypertens 2007;25:1105–87.
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protection using beta-blockers: a critical review of the evidence. J Am
Coll Cardiol 2007;50:563–72.
8. Medical Research Council. Medical Research Council trial of treat-
ment of hypertension in older adults: principal results. MRC Working
Party. BMJ 1992;304:405–12.
9. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension:
is it a wise choice? Lancet 2004;364:1684–9.
10. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers
remain first choice in the treatment of primary hypertension? A
meta-analysis. Lancet 2005;366:1545–53.
11. Bangalore S, Sawhney S, Messerli FH. Relation of beta-blocker–
induced heart rate lowering and cardioprotection in hypertension.
J Am Coll Cardiol 2008;52:1482–9.
12. Williams B, Lacy PS, Thom SM, et al. Differential impact of blood
pressure-lowering drugs on central aortic pressure and clinical out-
comes: principal results of the Conduit Artery Function Evaluation
(CAFE) study. Circulation 2006;113:1213–25.
Key Words: beta-blockers y cardiovascular events y heart rate y
JACC Vol. 52, No. 18, 2008
October 28, 2008:1490–1
Beta-Blockers in Hypertension