Individualized Beta-Blocker Treatment For High Blood Pressure Dictated by Medical Comorbidities: Ind

ADVERTISEMENT
SCIENCE VOLUNTEER WARNING SIGNS Search  Advanced Search DONATE
Hello Guest!
MY ALERTS SIGN IN JOIN
OpenAthens/Shibboleth »
Submit your article  
AHA Journals Journal Information All Issues Subjects Features Resources & Education For Authors & Reviewers

 
 
 
 
 
 

Home Hypertension Vol. 79, No. 6 Individualized Beta-Blocker Treatment for High Blood Pressure Dictated by Me…
  
   
Details Related References Figures
 FREE ACCESS Individualized Beta-Blocker Treatment for High
REVIEW ARTICLE
Blood Pressure Dictated by Medical
 PDF/EPUB
Comorbidities: Indications Beyond the 2018
European Society of Cardiology/European
Society of Hypertension Guidelines
 Tools  Share
Giuseppe Mancia, Sverre E. Kjeldsen , Reinhold Kreutz , Atul Pathak,
Guido Grassi and Murray Esler
Jump to Originally published 5 Apr 2022
June 2022
https://doi.org/10.1161/HYPERTENSIONAHA.122.19020
Abstract Hypertension. 2022;79:1153–1166 Vol 79, Issue 6
Other version(s) of this article 
The 2018 Guidelines and
Treatment With Beta-
ADVERTISEMENT
Blockers
Abstract
Other Cardiac
Indications for Beta- Several hypertension guidelines have removed beta-blockers
Blocker Treatment from their previous position as first-choice drugs for the
Noncardiac Indications treatment of hypertension. However, this downgrading may not
for Beta-Blocker be justified by available evidence because beta-blockers lower
Treatment Related to the
blood pressure as effectively as other major antihypertensive
Peripheral Circulation
drugs and have solid documentation in preventing cardiovascular
Discussion complications. Suspected inconveniences of beta-blockers such
Article Information as increased risk of depression or erectile dysfunction may have
been overemphasized, while patients with chronic obstructive
Footnotes pulmonary disease or peripheral artery disease, that is,
References conditions in which their use was previously restricted, will
benefit from beta-blocker therapy. Besides, evidence that from Article Information
eLetters
early to late phases, hypertension is accompanied by activation
of the sympathetic nervous system makes beta-blockers Metrics
Supplemental Material
pathophysiologically an appropriate treatment in hypertension.
Beta-blockers have favorable effects on a variety of clinical
conditions that may coexist with hypertension, making their use
either as specific treatment or as co-treatment potentially
common in clinical practice. Guidelines typically limit See more details
recommendations on specific beta-blocker use to cardiac Picked up by 1 news outlets
conditions including angina pectoris, postmyocardial infarction, Posted by 13 X users
or heart failure, with little or no mention of the additional On 1 Facebook pages
cardiovascular or noncardiovascular conditions in which these 71 readers on Mendeley
drugs may be needed or preferred. In the present narrative
review, we focus on multiple additional diseases and conditions Article Metrics View all metrics
that may occur and affect patients with hypertension, often more
frequently than people without hypertension, and that may favor
the choice of beta-blocker. Notwithstanding, beta-blockers Downloads Citations
represent an in-homogenous group of drugs and choosing beta-

blockers with documented effect in prevention and treatment of
800
disease is important for first choice in guidelines.
600
400
200
0
In recent years, several hypertension and cardiovascular AP
R
20
JU
L
20
OC
T
20
JA
N
20
AP
R
20
JU
L
20
OC
T
20
JA
N
20
prevention guidelines1–4 have removed beta-blockers from their 22 22 22 23 23 2 3 23 24
previous position as first-choice drugs for the treatment of

7,488 16
hypertension, recommending their use only for some specific
clinical conditions or, in absence of or insufficient blood pressure
Total First 30 Days 6 Months 12 Months
(BP) lowering response to initially administered agents, as a later
treatment step. However, this downgrading may not be justified
Total number of downloads
by the available evidence because beta-blockers lower elevated and citations
BP as effectively as all other major antihypertensive drugs.5

Furthermore, beta-blockers have been shown to sizably reduce
the risk of cardiovascular outcomes in placebo-controlled trials.6 Sources of Funding
Finally, with 2 exceptions,7,8 in several randomized clinical trials The present work had no funding or
(RCTs), beta-blockers have shown an association with secretarial assistance.
cardiovascular outcomes similar to that of other major
© 2022 American Heart Association, Inc.
antihypertensive drugs,9–14 with a superimposable or an only
slightly less evident overall protective effect in trial meta- https://doi.org/10.1161/HYPERTENSIONAHA.
analyses.6,15,16 As mentioned by the 2018 guidelines of the 122.19020
European Society of Cardiology (ESC) and the European Society PMID: 35378981
of Hypertension (ESH),1 the observation that beta-blockers are
less protective against stroke than other drugs in meta-analyses Originally published April 5, 2022
of RCTs17 should be interpreted with caution for several reasons.
(1) This difference may have originated from between-trial small
differences in achieved BP, which can hardly be neutralized by
Keywords
adjustment procedures and to which stroke is especially
sensitive.8,18,19 (2) No evidence has ever been obtained of a antihypertensive drugs beta-blockers
direct damaging effect of beta-blockers on cerebral tissue and its
blood flow autoregulation. (3) Beta-blockers substantially reduce blood pressure heart rate
the risk of stroke in placebo-controlled trials on hypertensive
patients.17 On the other side, recent observations provide hypertension
evidence that favors the use of beta-blockers. That is, PDF download
inconveniences of beta-blockers such as increased risk of
depression20 or erectile dysfunction21 seem to be
overemphasized. ADVERTISEMENT
These drugs now have been shown to be protective and safe in

conditions such as chronic obstructive pulmonary disease
(COPD) and peripheral artery disease, for which their use has
been traditionally restricted or even regarded as
contraindicated.22,23 Importantly, from early to late phases,
hypertension and related diseases and conditions such as heart
failure (HF), ischemic heart disease, obesity, or obstructive sleep
apnea are accompanied by activation of the sympathetic nervous
system,24 which makes beta-blockers pathophysiologically an
appropriate treatment in individuals with elevated BP.
Further important advantages of beta-blockers are their favorable

effects on a large variety of clinical conditions that may coexist Subjects
with hypertension, thus making their use either as specific
Heart Failure
treatment or as co-treatment potentially common in clinical High Blood Pressure
practice. Although in line with the growing tendency to Hypertension
personalize medical treatments, this is not or only partly,
addressed by most guidelines. Guidelines limit recommendations
on beta-blocker use typically to cardiac conditions including
angina pectoris, heart rate control, postmyocardial infarction or
HF, with little or no mention of several additional cardiovascular
or noncardiovascular conditions in which these drugs may be
needed or preferred. In the present narrative review, we aim to
focus on these additional diseases and conditions, which may
occur and affect patients with hypertension, often more
frequently than people without hypertension, favoring a beta-
blocker in the choice of drug treatment. A more detailed
assessment of BP lowering effects of beta-blockers in
monotherapy in uncomplicated, essential hypertension is
discussed in the Supplemental Material S1. Because some of us
are also members of the European Guidelines Committee, we
have in the Supplemental Material S2 added a short
organizational explanation for why the present review is needed.
We have further elaborated on our motivation and the general
use of beta-blockers in medicine in the Supplemental Material S3
and the benefits of combinations RAS-blocker/calcium channel
blocker/diuretic in Supplemental Material S4. Our focus is on
chronic conditions where comorbid hypertension should often,
incidentally and/or as consequence of comorbid disease‚ be
treated with a beta-blocker as a preferable choice compared to
other antihypertensive drugs. In this context, we find it too
extensive to discuss the sympatholytic effects of other
antihypertensive drugs such as the indirect effects of blockers on
the renin-angiotensin-aldosterone system or α-blockers.
The 2018 Guidelines and Treatment With Beta-Blockers

The 2018 ESC/ESH Hypertension Guidelines stated the following
recommendations regarding the usage of beta-blocker.1 Beta-
blockers have been shown to be particularly useful for the
treatment of hypertension in specific situations such as
symptomatic angina, for heart rate control, postmyocardial
infarction, HF with reduced ejection fraction and as an alternative
to ACE (angiotensin-converting enzyme) inhibitors or ARBs in
younger hypertensive women planning pregnancy or of child-
bearing potential.” Treatment with beta-blockers is
recommended by the European guidelines in the text describing
prevention and treatment of atrial fibrillation, and in case of aortic
dissection. These comorbidities (Table 1) are well-recognized
indications for treatment of hypertension with beta-blocker and
therefore not discussed further in detail in the present article‚
with 2 exceptions namely benefits of heart rate lowering and HF
with preserved ejection fraction (HFpEF).
Table 1. The 2018 ESC/ESH Hypertension Guidelines Mention

Beta-Blocker Treatment if Hypertensive Patients Suffer the
Following Concomitant Diseases or Conditions
Symptomatic angina
Postmyocardial infarction
HFrEF
Women with childbearing potential/planning pregnancy
Heart rate control (<80 beats/min)
Atrial fibrillation
Prevention
Rhythm control
Heart rate (frequency) control
Aortic dissection
ESC indicates European Society of Cardiology; ESH,

European Society of Hypertension; and HFrEF, Heart failure
with reduced ejection fraction.
Beta-Blockers and Heart Rate Reduction

Elevated resting heart rate values are detectable in a consistent
fraction of hypertensive patients as schematically illustrated in
Figure 1, particularly young or middle-aged mild-to-moderate
hypertensive patients with a so-called hyperkinetic
circulation.24,25 Elevated heart rate in hypertensive patients has
detrimental effects on the cardiovascular system, increasing
cardiac work and myocardial oxygen demand, augmenting
arterial wall stress, decreasing arterial distensibility and
facilitating coronary plaque disruption.26 Taken together, these
adverse effects explain why increased heart rate represents an
independent risk factor in the hypertensive population,
associated with an elevated probability of development of fatal
and nonfatal cardiovascular events as well as target organ
damage, particularly at cardiac level.26 Evidence has been also
provided that elevated heart rate values at rest depend on the
alteration in cardiac autonomic regulation of sinus node activity,
reflecting in particular an increased sympathetic function and a
reduced parasympathetic tone to the heart. This is supported by
the recent finding that in hypertensive patients heart rate values
greater than 80 beats/minutes, a value indicated by recent
ESC/ESH guidelines,1 reflect an increased sympathetic
cardiovascular drive, as assessed by the microneurographic
technique and the assay of the circulating venous plasma levels
of the neuro-adrenergic transmitter noradrenaline.27 In
hypertensive patients with an elevated heart rate the cardiac
sympathetic outflow is specifically activated, evident in increased
cardiac noradrenaline spillover values.28 As far as the therapeutic
intervention is concerned, despite the lack of direct Randomized
Clinical Trial evidence, ESC/ESH guidelines recommend beta-
blockers as first choice drug treatment of the hypertensive
patients with resting heart rate values >80 beats/min. The
guidelines are recognizing the clinical relevance of reducing
elevated heart rate in this group of patients for decreasing
cardiac sympathetic overdrive and the related increase in
cardiovascular risk.1
Download figure | Download PowerPoint

Figure 1. Schematic relationship between plasma
catecholamines, heart rate, and blood pressure in
hypertension. Adr indicates adrenaline; BP, blood
pressure; HR, heart rate; and NA, noradrenaline.
The Use of Beta-Blocker Treatment in Patients With HF With Mid-

Range and Preserved Ejection Fraction
The 2018 ESC/ESH Hypertension Guidelines1 did not discuss HF
with mid-range (heart failure with medium range ejection fraction)
or HFpEF while the ESC HF guidelines make the point that there
is no specific drug treatment for HFpEF.29 However, the
SENIORS (Study of the Effects of Nebivolol Intervention on
Outcomes and Rehospitalisation in Seniors With HF)30
investigated nebivolol versus placebo in unselected patients with
HF in whom low ejection fraction was not a selection criterion,
and the results were positive for the primary end point
(composite of hospitalization for HF and death). In a prespecified
sub-group analysis, there was no difference in outcome (primary
end point) in patients with reduced compared to patients with
preserved ejection fraction.31
Though no RCT of beta-blocker treatment on composite death

and HF has been performed in patients with HFpEF, there is an
extensive use of free add-on beta-blockers in all RCTs performed
in this group of HF patients in whom hypertension is typically
extremely common. Up to 96% of the study participants had
hypertension irrespective of which HF agent was investigated in
the RCTs.32
Figure 2 illustrates more in detail the use of beta-blockers in

RCTs in HFpEF patients. Beta-blocker treatment was given as
free add-on to >55% of all patients groups irrespective of
placebo or active drug. In I-PRESERVE (Irbesartan in HF With
Preserved Systolic Function Trial),33 the use of beta-blocker
increased to 72% of the patients during the course of the trial. In
PARAGON (Angiotensin-Neprilysin Inhibition in HF With
Preserved Ejection Fraction)34 as many as 80% were on beta-
blockers at baseline. In EMPEROR-PRESERVED (Empagliflozin in
HF With a Preserved Ejection Fraction),35 87% were taking beta-
blocker at baseline in the placebo group and 86% in the
empagliflozin treatment group. Percentages at study end were
probably higher as it was shown in I-PRESERVE33 although
follow-up data on concomitant medications were not included in
other publications.34,35 Thus, dedicated HF trial investigators
treat most of the patients with typical hypertensive HF (HFpEF)
with beta-blockers. We have briefly commented upon this issue
also in the Supplemental Material S5.

Figure 2. Overview of the use of beta-blockers on
clinical indications in the randomized clinical trials of
patients with heart failure with preserved ejection
fraction (HFpEF). ACEi indicates angiotensin-converting
enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi,
angiotensin receptor blocker neprilysin inhibitor; CHARM-
PRES, Candesartan in patients with chronic heart failure
and preserved left ventricular ejection fraction; EMPEROR-
PRES, empagliflozin in heart failure with a preserved
ejection fraction; HFpEF, heart failure with preserved
ejection fraction; I-PRESERVE, Irbesartan in patients with
heart failure and preserved ejection fraction; MRA,
mineralocorticoid receptor antagonist; PARAGON,
Prospective Comparison of ARNI with ARB Global
Outcomes in HF with Preserved Ejection Fraction; PEP-
CHF, Perindopril in Elderly People with Chronic Heart
Failure; RCT, randomized clinical trial; SGLT2i, sodium
glucose cotransporter inhibitor; and TOPCAT, Treatment of
Preserved Cardiac Function Heart Failure With an
Aldosterone Antagonist.
Moreover, a recent individual patient-level analysis of RCTs

indicated that beta-blocker therapy improved left ventricular (LV)
ejection fraction, all-cause mortality and cardiovascular mortality
in patients with mid-range/mildly reduced ejection fraction (LV
ejection fraction 40%–49%) in patients in sinus rhythm to a
similar extent as in patients with HF with reduced ejection
fraction.36
Other Cardiac Indications for Beta-Blocker Treatment

There is a number of other cardiac indications for beta-blocker
treatment not covered in the 2018 ESC/ESH Hypertension
Guidelines (Table 2). These concomitant diseases or conditions
are complications of hypertension or they occur more frequently
in patients with hypertension than in normotensive people.
Table 2. Other Cardiac Indications for Treatment With Beta-

Blockers
Acute coronary syndrome
Chest pain
LQTS
HOCM, subaortic stenosis, septal thickness
Uncontrolled rapid atrial fibrillation combined with diltiazem or verapamil to

avoid toxic amiodarone
Paroxysmal supraventricular arrhythmias, ventricular arrhythmias, other

arrhythmias
Post ICD implantation
Attacks of tachycardia after PM implantation for tachy-brady syndrome
After CABG, valve and other major cardiac surgery, consider in HF with
medium range (HFmrEF) and HFpEF
Unpleasant palpitations
CABG indicates coronary artery bypass graft; ICD, implantable

cardioverter defibrillator; HF, heart failure; HFpEF, heart failure
with preserved ejection fraction; HOCM, hypertrophic
obstructive cardiomyopathy; LQTS, long QT syndrome; and
PM, pacemaker.
Acute and Chronic Coronary Syndromes

Chronic coronary syndrome relates to the indication of beta-
blocker treatment in postmyocardial infarction and symptomatic
angina pectoris, described in the hypertension guidelines.1,37 The
postmyocardial infarction RCTs were performed before
fibrinolytic treatment and invasive treatment with PCI and
implantation of stents were introduced,38,39 and beta-blocker
treatment was effective in preventing sudden cardiac death. All
these trials have reinforced the indication for beta-blocker
treatment of postmyocardial infarction in presence of additional
conditions. If there is hypertension, tachycardia, angina,
arrhythmias, HF, or ischemia because of incomplete myocardial
revascularization beta-blockers are indicated. This is the case
also for an unstable acute coronary syndrome with persistent
ischemia, angina pectoris, or arrhythmias, usually showing
ischemia on ECG or leakage of troponins into blood. In these
patients, beta-blockers are first-choice treatment regardless
whether patients have hypertension or not. In postmyocardial
infarction patients in stable conditions and without any of these
strong indications for beta-blocker treatment several ongoing
RCTs may clarify the beta-blocker indication.
Unspecific Chest Pain, Reduced Coronary Reserve, and

Myocardial Infarction With Nonobstructive Coronary Arteries
Beta-blockers may be indicated for uncharacteristic or atypical
chest pain, which may not necessarily be related to
macrovascular coronary disease. In a number of patients, main
epicardial coronary arteries are open and normal, but chest pain
still has a cardiac origin because of extensive structural
alterations of the microcirculation. This is typically associated
with hypertension, which increases the wall thickness and wall-
to-lumen ratio of small precapillary arteries and causes capillary
rarefaction (The Hallmark of Hypertension).40 Compromised
arterial microcirculation is compatible with reduced coronary
reserve41—these days referred to as myocardial infarction with
non-obstructive coronary arteries,42 a term used to describe
patients with a diagnosis of myocardial infarction who are found
to have nonobstructive or normal coronary arteries following
coronary angiography. With these conditions chest pain has
been more common in nonbeta-blocker arms of large outcome
trials, justifying the indication for beta-blocker treatment. For
example, in the close out phase of the LIFE (Losartan
Intervention for End point Reduction in Hypertension) Study,7
patients were recommended further treatment with both losartan
and atenolol irrespective of in-trial blinded medication. One of
the reasons beside insufficient BP control was reports of
significantly more unspecific chest and back pains on losartan
(23%) versus the atenolol (20%) treated patients with LV
hypertrophy.7
Long QT Syndrome
Long QT syndrome is an abnormal feature of the heart’s electrical
system that can lead to a potentially life-threatening arrhythmia
called torsades de pointes. Torsades de pointes may result in
ventricular fibrillation, syncope (fainting), or sudden cardiac
death. Catecholaminergic polymorphic ventricular tachycardia
may for example benefit from nadolol versus others beta-
blockers.43 When Long QT syndrome is diagnosed, it is
important to remove any triggering mechanism including drugs
that prolong QT and may cause the condition. Long QT
syndrome may have a genetic nature but even when acquired it
may be difficult to resolve. Thus, antiarrhythmic drugs as beta-
blockers maybe indicated,44 especially in people with
hypertension. Some patients may nevertheless need a
pacemaker or an implantable cardiodefibrillator.45
LV Outflow Tract Obstruction

Various cardiac conditions are characterized by a LV outflow tract
obstruction towards the aortic valve. One of them may be due to
extensive thickness or hypertrophy of the septum, a condition
common in patients with hypertension,46 or to a classic subaortic
stenosis with loud and high frequent systolic murmur.
Alternatively, the cause can be a hypertrophic obstructive
cardiomyopathy at an advanced stage.47 Treatment with beta-
blockers will slow down heart rate, increase the length of
diastole, and thus improve ventricular filling.48 Auscultation of
patients with subaortic stenosis soon after initiation of beta-
blocker therapy may reveal their effects by demonstrating that
the preceding systolic murmur is weaker or even absent. This is
a sign of successful treatment.
Uncontrolled Rapid Atrial Fibrillation and Combination of Beta-

Blocker and Nondihydropyridine Calcium Antagonist
Rapid atrial fibrillation is treated with a beta-blocker or a
nondihydropyridine calcium channel blocker such as diltiazem or
verapamil, although beta-blocker is the option of choice if HF
with reduced ejection fraction is involved, because of the
pronounced negative-inotropic effect of nondihydropyridine
CCBs.29 Moreover, unlike beta-blockers, drug interactions must
be considered when using verapamil or diltiazem, due to their
inhibitory effect on drug transport mediated by P-glycoprotein
and metabolism by the cytochrome P 450 3A4 enzyme. The
latter may affect several other cardiovascular and
noncardiovascular drugs‚ including direct oral anticoagulants for
which co-administration with nondihydropyridines would result in
higher drug levels and thereby increase bleeding risk.49
However, there are patients who do not respond satisfactorily to

separate treatment with either drug class, in which a cautious
use of their combination may be indicated. This is particularly the
case when single agent treatment reduces heart rate to 110 to
120 beats/min or less, but patients are still short of breath,
complain of palpitations, or feel uncomfortable. The combination
of beta-blocker with diltiazem or verapamil may also be a
treatment alternative to avoid the toxic side effects of
amiodarone. Their administration alone or in combination may
reduce symptoms and improve well-being in hypertensive
patients with high risk of atrial fibrillation who may have an
increased LV mass or LV hypertrophy, that is, conditions in which
slowing heart rate down to <100 beats/min or lower (ideally <84
beats/min) improves filling of the LV in diastole.
One may wonder whether the combination of beta-blocker and

nondihydropyridine CCB may cause an excessive reduction of
heart rate or even cardiac arrest. However, in the NORDIL (Nordic
Diltiazem) study, about 700 patients took this drug combination
(mostly because of crossover between open treatment arms) and
syncope or need for pacemaker implantation was not reported.50
Because crossover between randomized study arms was
foreseen, the NORDIL investigators assessed the safety issue on
beforehand. The question was whether the combination could
cause severe bradycardia and/or cardiac arrest. However, in
clinical practice, the beta-blocker plus diltiazem or plus
verapamil combination treatment had not been reported to cause
severe bradycardia with the subsequent need for pacemaker
treatment in the NORDIL countries (Norway and Sweden) except
for a very few patients.51 It should nevertheless be mentioned
that worsening of HF could happened in selected patients
because of excessive negative inotropic and chronotropic
effects, in which case amiodarone would be the remaining
treatment choice of therapy usually combined with beta-
blocker.29
Other Arrhythmias, Cardiac Devices, Palpitations, and Cardiac

Surgery
There are various paroxysmal supraventricular arrhythmias,
ventricular arrhythmias, and other tachy-arrhythmias with an
indication for beta-blocker treatment not specifically mentioned
or described in the 2018 ESC/ESH hypertension guidelines.1
Patients are routinely given beta-blockers after cardiodefibrillator
implantation and in tachy-bradycardia syndrome (after PM
implantation) to suppress the attacks of tachycardia and
unneeded device activity. In absence of heart disease, some
people are bothered by unpleasant palpitations, which may be
associated with findings of X-systolic beats or not, at the work
up of the cardiologist. Although, no prognostic documentation is
available, treatment with beta-blockers may relieve symptoms. In
the first days or even longer after coronary artery by-pass graft
surgery (CABG), valve surgery or other major cardiac surgery the
myocardium maybe particular sensitive to arrhythmias and beta-
blocker treatment has to be frequently used—whether patients
have hypertension or not. Cardiology textbooks provide further
details on the conditions mentioned in this paragraph.
Noncardiac Indications for Beta-Blocker Treatment

Related to the Peripheral Circulation
There is a number of indications for beta-blocker treatment
related to the peripheral circulation (Table 3).
Table 3. Indication for Beta-Blocker Treatment Related to

Peripheral Circulation
Emergency, urgency, and parenteral administration of labetalol
Perioperative hypertension
Major noncardiac surgery
Excessive pressor response to exercise and stress
Hyperkinetic heart syndrome
POTS
Orthostatic hypertension
Obstructive sleep apnea syndrome
Peripheral arterial disease with claudication
Portal hypertension, cirrhosis-related oesophageal varices and recurrent

variceal bleeding
Pregnancy related disorders (eclampsia, preeclampsia)
POTS indicates postural orthostatic tachycardia syndrome.
Emergency, Urgency, and Parenteral Administration of Labetalol

For simplicity reasons, it is referred to textbooks.
Perioperative Hypertension and Major Noncardiac Surgery

The 2017 ACC/AHA defines perioperative hypertension as a BP
≥160/90 mm Hg or a systolic BP elevation ≥20% of the
preoperative value that persists for longer than 15 minutes. Beta-
blockers is a first treatment choice in patients undergoing
vascular procedures or in those with an intermediate or high risk
of cardiac complications.52 Postcarotid endarterectomy
hypertension is a well-recognized phenomenon closely related to
surgical complications in which the perioperative use of beta-
blockers protects against the BP elevation and contributes to
stabilizing the postoperative peak systolic BP for days after the
intervention.53 Beta-blocker treatment is also widely used for any
type of major noncardiac surgery associated with an increased
response to the stressful condition or environment, which can
make the body vulnerable to untoward outcomes. Beta-blockers
attenuate this stress response, resulting in a slowing of heart rate
and a fall in BP. On one side, such effects are desirable to fight
the stress response, but the same effects, if pronounced, may
cause very low BP and heart rate.54 Thus, beta-blocker use for
major noncardiac surgery is controversial unless patients have
known cardiac disease including history and findings by
presurgical assessment.
Excessive Pressor Response to Exercise and Mental Stress and

Hyperkinetic Heart Syndrome
Excessive elevations of BP induced by physical exercise and/or
mental stress and beta-blocker treatment may be a good
choice.55
Hyperkinetic heart syndrome may occur in some hypertensive

individuals who have a higher heart rate and stroke volume at
rest and thus a higher cardiac output than hypertensive patients
without this particular syndrome. Therefore, BP is high although
peripheral resistance is lower than normal. After beta-adrenergic
blockade,56 heart rate and cardiac output decrease, whereas
peripheral resistance increases. Mean BP mostly remains
unchanged.
Postural Orthostatic Tachycardia Syndrome and Orthostatic or

Postural Hypertension
Postural orthostatic syndrome is characterized by an excessive
tachycardia, quantified as either an increase of 30 beats per
minute or as a rate of >120 beats per minutes after up to half an
hour of standing. Distressing symptoms are common and so is
beta-blocker prescribing. Orthostatic or postural hypertension is
a less well-known form of hypertension that occurs abruptly
when someone moves into an upright position. An increase in BP
of 20 mm Hg or more when standing is the diagnostic criterion. In
severe cases, orthostatic hypertension can result in patients
experiencing the same complications that they would with
regular hypertension. However, in the majority of patients with
orthostatic hypertension, symptoms are only present in the
upright position. Beta-blocker is a natural choice for treating
postural orthostatic tachycardia syndrome57,58 while beta-
blockers are used with much less justification in the other
orthostatic intolerance variants including nonpostural orthostatic
syndrome forms of orthostatic hypertension. In other words,
beta-blockers do not directly influence orthostatic intolerance per
se apart from postural orthostatic tachycardia syndrome.
Obstructive Sleep Apnoea Syndrome

This syndrome is of interest to various medical fields. It is
certainly of interest in the present context because obstructive
sleep apnoea is common in obese hypertensive patients in
whom it further activates the sympathetic nervous system. This
justifies treatment with beta-blockers.
Peripheral Arterial Disease with Claudication

Peripheral arterial disease with claudication, the smokers’ leg, is
a common condition characterized by ischemia of skeletal
muscle tissue in the lower limbs, caused by extensive arterial
atherosclerosis. Beta-blocker treatment achieve anti-ischemic
effects and relieve pain.23,59 Dihydropyridine CCBs may have
similar anti-ischemic effects and combine with beta-blocker on
this indication. Smokers frequently have COPD. One should
always be alert regarding worsening of pulmonary function
(increased airway resistance) when treating patients with
peripheral artery disease with beta-blockers (Table 5).
Nonselective beta-blockers such as propranolol or timolol seem
to be worse compared to the selective beta-1 blockers, or alpha-
beta blockers. We refer to the section on COPD in the text below.
Portal Hypertension, Liver Cirrhosis–Related Oesophageal

Varices, and Recurrent Variceal Bleeding
Treatment with beta-blockers is widely recommended because
these drugs lower the portal pressure and prevent life-
threatening bleedings.60
Pregnancy-Related Disorders (Eclampsia, Preeclampsia)

In hypertension in pregnancy and pregnancy-related disorders
(eg, preeclampsia and eclampsia), blockers of the renin-
angiotensin system and diuretics are not recommended,1 while
alpha-methyldopa, nifedipine, and the unique beta-blocker
labetalol with an additional alpha-blocking mode of action are
recommended as first treatment choice.61 However, as recently
emphasized, these therapeutic options are based on small
individual investigations and recommendations vary between
national and international guidelines, while there is no clear
evidence that one drug is preferable to another.1 This applies
also to other beta-blockers including metoprolol and bisoprolol,
which are considered to be safe in pregnancy and are used in
many European countries, particularly in countries in which
labetalol is not available (eg, Germany), due to its hepatotoxic
effect that may also occur in pregnancy.62
Indications for Beta-Blocker Treatment Not Directly Related to

the Heart or Peripheral Circulation
There is a number of indications for beta-blocker treatment not
directly related to the heart or peripheral circulation (Table 4).
Table 4. Other Indications for Beta-Blocker Treatment Not

Directly Related to the Heart or Peripheral Circulation
COPD
Diabetes
Thyrotoxicosis, hyperthyroidism, thyroiditis, and Graves’ disease
Hyperparathyroidism in uremia
Migraine headache
Essential tremor
Glaucoma
Performance anxiety and anxiety disorders
Olympic sports (negative) as doping and sabotage
Psychiatric disorders (posttraumatic stress)
COPD indicates chronic obstructive pulmonary disease.
Chronic Obstructive Pulmonary Disease

As a general warning, one should always be alert for worsening
of pulmonary function with increased airway resistance when
giving beta-blockers to patients with pulmonary diseases (Table
5).
Table 5. Various Problems With the Use of Beta-Blockers to

Treat Concomitant Diseases and Disorders in the Treatment
of Hypertension
Worsening of bronchial asthma (increased airway

Nonselective
resistance) (also with low beta-1 selectivity as for
beta-blockers
atenolol)
Nonselective Male impotency—may choose vasodilating beta-

beta-blockers blocker
Nonselective Lower HDL cholesterol, increase TG, may cause

beta-blockers type-2 diabetes
Bradycardia, occasional need for pacemaker, in

Nonselective general lowering heart rate too much in the elderly
timolol with beta-blocker treatment may cause serious
adverse event (Supplemental Material S7)
Nonselective
Occasional proarrhythmic effect limits the use
sotalol
Intrinsic
Insufficient reduction of heart rate, no beneficial
sympathomimetic
effect in heart failure
activity
Hydrophilic beta- Do not pass blood-brain barrier, alternative if

blockers unpleasant dreaming
Beta-1 selective
Ultra-short acting, emergency use only
esmolol
Inferior in 2 RCTs (vs losartan, LIFE, and vs

Beta-1 selective
amlodipine, ASCOT) and untoward metabolic effects
atenolol
like nonselective beta-blockers indicated above
May mask symptoms of hypoglycemia and thus

Beta-blockers in
impair awareness particularly in patients with type-1
type-1 diabetes
diabetes or patients treated with insulin
Beta-blockers in
Labetalol and metoprolol considered safe
pregnancy
ASCOT indicates Anglo-Scandinavian Cardiac Outcomes Trial;

HDL, high-density lipoprotein; LIFE, Losartan Intervention for
End Point Reduction in Hypertension; RCT, randomized
controlled trial; and TG, triglycerides.
Patients with COPD frequently have coronary heart disease or

peripheral arterial disease because of their smoking habits.
However, patients with COPD have frequently been excluded
from treatment with beta-blockers, because of the unjustified
fear that blocking beta2-receptors in the bronchial system could
put these patients at risk. This was pointed out many years
ago22,63 and reiterated more recently.51 Importantly, a recent
meta-analysis64 demonstrated that the use of beta-blockers
(including both beta1- selective and nonselective agents) in
patients with COPD and cardiovascular disease is not only safe
but also reduces their all cause and in-hospital mortality. Of
interest, this analysis indicated also that beta1-selective beta-
blockers may even reduce COPD exacerbations.65 In addition,
cardio-selective beta-blockers do not affect the action of
bronchodilators but reduce the heart rate acceleration caused by
their use.65 It should be mentioned, however, that patients with
classical pulmonary asthma may worsen their condition by use of
nonselective beta-blockers or agents with low beta1-selectivity.
Diabetes
Patients with diabetes may occasionally experience
hypoglycemia and thus impaired awareness particularly in
patients with type 1 diabetes or patients treated with insulin
(Table 5). Beta-blockers in general may mask symptoms of
hypoglycemia, which are activation of the sympathetic nervous
system including tachycardia. However, patients with diabetes
may because of neuropathy, have silent ischemia in their
myocardium and elsewhere and may benefit from beta-blocker
treatment. Because of an extensive destruction of the
microcirculation type 2 diabetes is also a main cause of HF and,
though not proven specifically, probably the cause of the high
prevalence of type-2 diabetes in patients with HFpEF and one of
the reasons for the increasing concomitant use of beta-blockers
in RCTs of HFpEF medications (Figure 2).
First and second generation beta-blockers are associated with

increased incidence of new onset diabetes shown in several
RCTs including in LIFE7 and ASCOT (Anglo-Scandinavian
Cardiac Outcomes Trial).8 The importance of such findings is
uncertain as it could simply be earlier de-masking of latent type-
2 diabetes which would then receive more intensified preventive
treatment. First- and second-generation beta-blockers are also
associated with apparently unfavorable changes in blood lipids
(Table 5).
Thyrotoxicosis, Hyperthyroidism, Thyroiditis, and Grave’s Disease

In patients with thyrotoxicosis (thyroid storm) or symptomatic
hyperthyroidism, thyroiditis, and Graves’ disease, the excess of
thyroid hormone production and secretion may result in
increased heart rate, tremor, and nervousness. Propranolol is the
most widely studied nonselective beta-blocker to treat the
increased heart rate and tremor under these circumstances.65
Beta-blocker may additionally reverse some of the reduced
systemic vascular resistance associated with the hormonal
disease and inhibit the peripheral conversion of T4 to the more
biologically active hormone, T3.66 The American Association of
Clinical Endocrinologists Medical Guidelines for the Evaluation
and Treatment of Hyperthyroidism and Hypothyroidism67 have for
many years discussed the use of beta-blockers in conditions
characterized by an excess of thyroid hormones without
specifically recommending one beta-blocker over another.
Hyperparathyroidism in Uremia
Various beta-blockers suppress PTH secretion in patients with
uremia and hyperparathyroidism.68
Migraine Headache
Beta-blockers may prevent migraine or reduce the severity of
attacks. Efficacy has been established for metoprolol,
propranolol, and timolol, it is probable for atenolol and nadolol,
and possible for nebivolol and pindolol. Timolol and propranolol
are Food and Drug Administration approved for migraine
prevention69 while off label (unapproved) use of metoprolol is
also common.
Essential Tremor
Propranolol has been used to treat essential tremor for more than
40 years. Other beta-blockers, for example, metoprolol, may also
be effective depending on the case.70
Glaucoma
Topical beta-blockers reduce intraocular pressure by decreasing
the production of aqueous humor. Oral beta-blockers also
reduce intraocular pressure, but they are not used primarily to
treat or prevent glaucoma because of the systemic effects. If
used for other indications, for example, hypertension or cardiac
disease, lower intraocular pressure may be a major additional
benefit especially in the elderly. However, in the elderly both
topical and systemic co-administration of beta-blockers is
frequently observed71 and may result in additive effects including
the risk of bradycardia. Hence, topical administration of timolol
eye drops72 is a potent treatment for glaucoma that may cause
bradycardia and other systemic effects. Some patients with a
strong need of timolol against glaucoma may even need
pacemaker implantation because of the associated bradycardia.
Anxiety Disorders and Performance Anxiety

In psychiatry, beta-blockers are used in the treatment of anxiety
disorders with somatic manifestations such as palpitations,
sweating, and tremor.73 As such, performance anxiety that may
affect public speakers, musicians, or those taking an examination
also seem to be well suited for beta-blocker treatment. Beta-
blockers have a relaxing effect on muscle function, gaining the
drug class a popular reputation as illegal, performance-
enhancement drugs for athletes who benefit from the adrenaline-
blocking effects of the medication. Some athletes use
propranolol specifically for its anxiety-reducing effects, resulting
in steadier hands, an even heart rate and an increased ability to
focus. From 2010, beta-blockers were banned by the World Anti-
Doping Agency for all Olympic sports, including archery,
gymnastics, shooting, and golf.74 Athletes who need beta-
blockers for other indications must therefore stop taking this
treatment for several days (depending on the halflife of agents)
before competition. Further, regarding sport activities, timolol eye
drops are so potent that mixed in sport drinks they ruin chances
of high-level performance (and for example Olympic medals in
runners).
Panic Disorder
In panic disorder, beta-blockers are commonly prescribed75 for
symptom relief, combined with cognitive behavior therapy and/or
a selective serotonin reuptake inhibitors and/or a
benzodiazepine. This joins performance anxiety as a psychiatric
comorbidity treated with beta-blockade.
Posttraumatic Stress Disorder

The National Institute of Mental Health (Bethesda, MD) reports
that approximately 5.2 million Americans experience
posttraumatic stress disorder each year.76 Posttraumatic stress
disorder can be severely debilitating and diminish quality of life
for patients and those who care for them. Studies have indicated
that beta-blocker treatment reduces consolidation of emotional
memory. When administered immediately after a psychic trauma,
it is efficacious as a prophylactic for posttraumatic stress
disorder.77
Discussion
We have scrutinized the medical field for diseases and conditions
for which beta-blocker treatment is indicated in patients with
hypertension. Tables 1 to 4 summarize our findings‚ that there
are roughly 50 different diseases and conditions documented to
benefit from beta-blocker treatment. Thus, an overwhelming
number of diseases and conditions needs consideration for beta-
blocker treatment in patients with hypertension compared with
those few key indications mentioned up front in the guidelines.1
In general, as a thumb rule, beta-blockers with higher beta1-
selectivity are indicated in a large number of cardiovascular
diseases while nonselective beta-blockers are indicated for
endocrine diseases, anxiety, and other psychiatric disorders and
more when the aim of the beta-blocker treatment is to target
noncardiovascular tissue in general. However, this is not always
so clear-cut and we have not aimed to discuss this topic in detail
as we feel it is beyond the question of beta-blocker as first
choice in the treatment of hypertension.
There are also problems related to treatment with beta-blockers,

which are important to highlight, and which we have touched
upon in this review. We have summarized the most common
problems in Table 5 and partly also mentioned how to resolve
them when they appear. Although observational data from the
RCTs clearly show morbidity and mortality benefits of keeping
heart rate below approximately 80 to 84 beats/min, lowering
heart rate further below 70 toward 60 beats/min in the elderly
hypertensive patients may be related to serious adverse and
even cardiovascular events and should be prohibited
(Supplemental Material S6).
Our main point is that beta-blocker treatment is indicated for

numerous diseases and conditions that patients may suffer from
concomitant with hypertension. In a time developing toward
personalized medicine, there are multiple opportunities for
targeting both hypertension and the concomitant disease with
the same treatment namely a beta-blocking drug. Hypertension
is a risk factor for more or less all cardiac and vascular diseases,
which we have reviewed, and hypertension may result from some
of the other diseases such as hyperthyroidism. This means that
more patients with hypertension have these concomitant
diseases and conditions than have people with normal BP. This is
a general statement from our side, which we have not attempted
to support with exact data in as much as this point does not
affect the main message of this article. However, it could be of
interest in the future to investigate in details fractions of
hypertensive patients who suffer from the various concomitant
diseases.
It is quite striking that beta-blocker treatment is indicated in

common diseases such as COPD22,63–65 and peripheral arterial
disease. For many years, physicians and the RCTs that were
performed excluded patients with these diseases from therapy
with beta-blockers. Reasons could be for example lack of
separation between pulmonary asthma and COPD—2 very
different diseases of the lungs.
Overall‚ beta-blockade is a key principle of treatment in

medicine. Beta-blockers inhibit the actions of adrenaline and
noradrenaline in various organs and systems as schematically
shown in Figure 3. This holds true from classic physiology with
the fright, fight, and flight reaction to mostly chronic diseases on
which beta-receptor stimulation has a worsening effect. Beta-
blocker treatment has been investigated in hypertension and
heart disease RCTs together with numerous other cardiovascular
drugs that lower BP at the same time, which we have illustrated
in Figure 4. Beta-blockers provide documented cardiovascular
prevention together with several other drugs and in particular
together with diuretics of the thiazide/thiazide-like type. In fact,
the overwhelming evidence for combination therapy with beta-
blockers comes from beta-blockers plus diuretics (Supplemental
Material S7). It is also good clinical practice to combine beta-
blockers with other cardiovascular drugs, for example,
dihydropyridine CCBs by buffering reflex tachycardia. There is
usually close connection with drugs that work in HF with those
drugs that provide cardiovascular prevention in hypertension.
Angiotensin receptor blocker neprilysin inhibitor,
mineralocorticoid receptor antagonist, and SGLT2i (sodium
glucose cotransporter 2 inhibitor) are drug classes that never
have been investigated for end point prevention in patients with
hypertension without HF or diabetes; however, all these drugs
lower BP substantially, and they have powerful protective effects
in HF of mostly hypertensive etiology. The Food and Drug
Administrations in the United States has approved angiotensin
receptor blocker neprilysin inhibitor, mineralocorticoid receptor
antagonist, and SGLT2i for treatment of HF irrespective of LV
ejection fraction. It means that these drugs lower hospitalizing
and mortality in patients with HFpEF, related to hypertension in
90% of these patients or more. Beta-blockers have been less
studied in HFpEF but as shown in Figure 2 the heart specialist
investigators in the HF RCTs gave almost all the study
participants concomitant beta-blocker treatment on clinical
indications.

Figure 3. Schematic overview of sympathetic
transmitter activity in which adrenaline facilitates
noradrenaline release. Adr indicates adrenaline; and NA,
noradrenaline.

Figure 4. Overview of drugs classes suited as first
choice combination treatments of hypertension. Solid
lines connect drug classes in combinations
documented to prevent cardiovascular complications in
hypertension, or hospitalization and death in
randomized placebo controlled clinical trials in patients
with heart failure with predominantly hypertensive
etiology. ACEi indicates angiotensin-converting enzyme
inhibitor; ARB, angiotensin receptor blocker; ARNi,
angiotensin receptor blocker neprilysin inhibitor; DH-CCB,
dihydropyidin calcium channel blocker (calcium-
antagonist); MRA, mineralocorticoid receptor antagonist;
and SGLT2i, sodium glucose cotransporter inhibitor.
Regarding the 2018 ESC/ESH Hypertension Guidelines,1 it

intuitively feels incorrect that beta-blocker treatment was
removed from the first-choice treatment in the core-treatment
strategy for uncomplicated hypertension, that is, in patients
without specific indications including cardiac conditions and in
younger women with or planning pregnancy.1 There are
numerous additional indications for beta-blocker treatment in
hypertension, which need assessment before any decision of not
giving beta-blocker for hypertension. Frequently, the choice
would then be that the physicians will prescribe beta-blocker,
and we wonder whether a more positive attitude for beta-blocker
as first choice should be indicated up front in the guidelines.1
Beta-blocker may be combined with all other BP lowering drugs;
regarding the nondihydropyridine CCBs diltiazem and verapamil
care should be taken if suspected HF is involved because of
combined negative chronotropic and inotropic effects, but for
heart rate control in uncontrolled rapid atrial fibrillation, a
common cause of hospitalization, this combination may be
excellent.50,51
Regarding hypertension and renal disease, it is well known that

beta-blockers are well tolerated and do not deteriorate renal
function. It has not been extensively investigated, but some data
suggest that renal tissue oxygenations improves if patients with
hypertension and renal artery stenosis are treated with beta-
blocker.78
In conclusion, we suggest that beta-blockers as a group of BP

lowering medication should again be included in the first choice
armamentarium of available antihypertensive drugs by the
guidelines.
Article Information
Acknowledgments
We thank the Centre Hospitalier Princesse Grace, Monte Carlo,
Monaco for generously paying for author payment charges.
Sources of Funding
The present work had no funding or secretarial assistance.
Nonstandard Abbreviations and Acronyms

angiotensin-converting enzyme
ACE
Anglo-Scandinavian Cardiac Outcomes

ASCOT Trial
chronic obstructive pulmonary disease

COPD
Empagliflozin in Heart Failure With a

EMPEROR-
Preserved Ejection Fraction
PRESERVED
European Society of Cardiology

ESC
European Society of Hypertension

ESH
heart failure
HF
heart failure with preserved ejection

HFpEF fraction
Irbesartan in Heart Failure With

I-PRESERVE Preserved Systolic Function Trial
left ventricular
LV
Angiotensin-neprilysin inhibition in
heart failure with preserved ejection
PARAGON
fraction.
Losartan Intervention for End Point

LIFE Reduction in Hypertension
Nordic Diltiazem
NORDIL
mineralocorticoid receptor antagonist

MRA
Study of the Effects of Nebivolol

Intervention on Outcomes and
SENIORS Rehospitalization in Seniors With Heart
Failure
sodium glucose cotransporter 2

SGLT2i inhibitor
Disclosures G. Mancia has received honoraria from Astra

Zeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic,
Menarini, Merck, Novartis, Recordati, Sandoz, Sanofi and Servier.
S.E. Kjeldsen reports lecture honoraria from Getz Pharma, Merck
Healthcare KGaA, Sanofi-Aventis and Vector-Intas. R. Kreutz
reports support for research by Bayer, honoraria for lectures from
Bayer, Berlin-Chemie/Menarini, Daiichi Sankyo, Ferrer, Merck,
Sanofi and Servier. A. Pathak has received honoraria from
Ablative Solution, Air Liquide, Astra Zeneca, Boehringer
Ingelheim, Medtronic, Menarini, Merck, Novartis, Recordati,
Recor Medical, Sanofi and Servier. G. Grassi has received
honoraria for lectures from Medtronic, Merck Healthcare KGaA,
and Servier. M. Esler reports honoraria for participating in the
Renal Denervation advisory boards of Medtronic (United States)
and SyMap (China).
Footnotes
The opinions expressed in this article are not necessarily those of
the editors nor the American Heart Association.
The Data Supplement is available with this article at

https://www.ahajournals.org/doi/suppl/10.1161/HYPERTENSION
AHA.122.19020.
For Sources of Funding and Disclosures, see page 1164.
Correspondence to: Sverre E. Kjeldsen, Institute of Clinical

Medicine, Medical Faculty, University of Oslo, Oslo, Norway,
Email s.e.kjeldsen@medisin.uio.no
Correspondence to: Reinhold Kreutz, Charité –
Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt-Universität zu Berlin, Institute of Clinical
Pharmacology and Toxicology, Berlin, Germany, Email reinhold.
kreutz@charite.de
References
1. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M,
Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, et
al; Authors/Task Force Members. 2018 ESC/ESH Guidelines for
the management of arterial hypertension: The Task Force for the
management of arterial hypertension of the European Society of
Cardiology and the European Society of Hypertension: the Task
Force for the management of arterial hypertension of the
European Society of Cardiology and the European Society of
Hypertension. J Hypertens. 2018; 36:1953–2041. doi:
10.1097/HJH.0000000000001940
Crossref | Medline | Google Scholar
2. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ,
Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA,
Jones DW, et al. 2017
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA
Guideline for the prevention, detection, evaluation, and
management of high blood pressure in adults: a report of the
american college of cardiology/american heart association task
force on clinical practice guidelines. J Am Coll Cardiol. 2018;
71:e127–e248. doi: 10.1016/j.jacc.2017.11.006
3. Unger T, Borghi C, Charchar F, Khan NA, Poulter NR,

Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS,
Tomaszewski M, et al. 2020 International society of hypertension
global hypertension practice guidelines. Hypertension. 2020;
75:1334–1357. doi: 10.1161/HYPERTENSIONAHA.120.15026
Link | Google Scholar
4. Jones NR, McCormack T, Constanti M, McManus RJ.

Diagnosis and management of hypertension in adults: NICE
guideline update 2019. Br J Gen Pract. 2020; 70:90–91. doi:
10.3399/bjgp20X708053 Crossref | Medline | Google Scholar
5. Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose
combination treatment with blood pressure lowering drugs:
analysis of 354 randomised trials. BMJ. 2003; 326:1427. doi:
10.1136/bmj.326.7404.1427
6. Thomopoulos C, Parati G, Zanchetti A. Effects of blood

pressure lowering on outcome incidence in hypertension: 4.
Effects of various classes of antihypertensive drugs–overview
and meta-analyses. J Hypertens. 2015; 33:195–211. doi:
10.1097/HJH.0000000000000447
7. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de

Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-
Pedersen O, et al; LIFE Study Group. Cardiovascular morbidity
and mortality in the Losartan Intervention For Endpoint reduction
in hypertension study (LIFE): a randomised trial against atenolol.
Lancet. 2002; 359:995–1003. doi: 10.1016/S0140-
6736(02)08089-3 Crossref | Medline | Google Scholar
8. Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG,

Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT,
et al; ASCOT Investigators. Prevention of cardiovascular events
with an antihypertensive regimen of amlodipine adding
perindopril as required versus atenolol adding
bendroflumethiazide as required, in the Anglo-Scandinavian
Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-
BPLA): a multicentre randomised controlled trial. Lancet. 2005;
366:895–906. doi: 10.1016/S0140-6736(05)67185-1
9. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG,

Kowey P, Messerli FH, Mancia G, Cangiano JL, Garcia-Barreto D,
Keltai M, et al; INVEST Investigators. A calcium antagonist vs a
non-calcium antagonist hypertension treatment strategy for
patients with coronary artery disease. The International
Verapamil-Trandolapril Study (INVEST): a randomized controlled
trial. JAMA. 2003; 290:2805–2816. doi:
10.1001/jama.290.21.2805 Crossref | Medline | Google Scholar
10. Wilhelmsen L, Berglund G, Elmfeldt D, Fitzsimons T,

Holzgreve H, Hosie J, Hörnkvist PE, Pennert K, Tuomilehto J,
Wedel H. Beta-blockers versus diuretics in hypertensive men:
main results from the HAPPHY trial. J Hypertens. 1987; 5:561–
572. doi: 10.1097/00004872-198710000-00009
11. Wikstrand J, Warnold I, Tuomilehto J, Olsson G, Barber HJ,

Eliasson K, Elmfeldt D, Jastrup B, Karatzas NB, Leer J.
Metoprolol versus thiazide diuretics in hypertension. Morbidity
results from the MAPHY Study. Hypertension. 1991; 17:579–
588. doi: 10.1161/01.hyp.17.4.579 Link | Google Scholar
12. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA.
10-year follow-up of intensive glucose control in type 2 diabetes.
N Engl J Med. 2008; 359:1577–1589. doi:
10.1056/NEJMoa0806470 Crossref | Medline | Google Scholar
13. Hansson L, Lindholm LH, Ekbom T, Dahlöf B, Lanke J,

Scherstén B, Wester PO, Hedner T, de Faire U. Randomised trial
of old and new antihypertensive drugs in elderly patients:
cardiovascular mortality and morbidity the Swedish Trial in Old
Patients with Hypertension-2 study. Lancet. 1999; 354:1751–
1756. doi: 10.1016/s0140-6736(99)10327-1
14. Medical Research Council Working Party. MRC trial of

treatment of mild hypertension: principal results. Br Med J. 1985;
291:97–104. doi: 10.1136/bmj.291.6488.97
15. Turnbull F, Neal B, Ninomiya T, Algert C, Arima H, Barzi F,

Bulpitt C, Chalmers J, Fagard R, Gleason A, et al; Blood Pressure
Lowering Treatment Trialists’ Collaboration. Blood pressure-
lowering treatment based on cardiovascular risk: a meta-analysis
of individual patient data. Lancet. 2014; 384:591–598. doi:
10.1016/S0140-6736(14)61212-5
16. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T,

Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure
lowering for prevention of cardiovascular disease and death: a
systematic review and meta-analysis. Lancet. 2016; 387:957–
967. doi: 10.1016/S0140-6736(15)01225-8
17. Thomopoulos C, Bazoukis G, Tsioufis C, Mancia G. Beta-

blockers in hypertension: overview and meta-analysis of
randomized outcome trials. J Hypertens. 2020; 38:1669–1681.
doi: 10.1097/HJH.0000000000002523
18. Turnbull F, Neal B, Ninomiya T, Algert C, Arima H, Barzi F,

Bulpitt C, Chalmers J, Fagard R, Gleason A, et al; Blood Pressure
Lowering Treatment Trialists’ Collaboration. Effects of different
regimens to lower blood pressure on major cardiovascular events
in older and younger adults: meta-analysis of randomised trials.
Br Med J. 2008; 336:1121–1123. doi:
10.1136/bmj.39548.738368.BE
19. Mancia G, Zanchetti A; European Society of Hypertension-

European Society of Cardiology. Choice of antihypertensive
drugs in the European Society of Hypertension-European Society
of Cardiology guidelines: specific indications rather than ranking
for general usage. J Hypertens. 2008; 26:164–168. doi:
10.1097/HJH.0b013e3282f52fa8
20. Riemer TG, Villagomez Fuentes LE, Algharably EAE,

Schäfer MS, Mangelsen E, Fürtig MA, Bittner N, Bär A, Zaidi
Touis L, Wachtell K, et al. Do β-blockers cause depression?
Systematic review and meta-analysis of psychiatric adverse
events during β-blocker therapy. Hypertension. 2021; 77:1539–
1548. doi: 10.1161/HYPERTENSIONAHA.120.16590
21. Farmakis IT, Pyrgidis N, Doundoulakis I, Mykoniatis I,

Akrivos E, Giannakoulas G. Effects of major antihypertensive
drug classes on erectile function: a network meta-analysis
[published online May 4, 2021]. Cardiovasc Drugs Ther. doi:
10.1007/s10557-021-07197-9.
https://link.springer.com/article/10.1007/s10557-021-07197-9
Crossref | Google Scholar
22. Hawkins NM, Petrie MC, Macdonald MR, Jhund PS, Fabbri
LM, Wikstrand J, McMurray JJ. Heart failure and chronic
obstructive pulmonary disease the quandary of Beta-blockers
and Beta-agonists. J Am Coll Cardiol. 2011; 57:2127–2138. doi:
10.1016/j.jacc.2011.02.020 Crossref | Medline | Google Scholar
23. Espinola-Klein C, Weisser G, Jagodzinski A, Savvidis S,

Warnholtz A, Ostad MA, Gori T, Munzel T. β-Blockers in patients
with intermittent claudication and arterial hypertension: results
from the nebivolol or metoprolol in arterial occlusive disease trial.
Hypertension. 2011; 58:148–154. doi:
10.1161/HYPERTENSIONAHA.110.169169
24. Mancia G, Grassi G. The autonomic nervous system and

hypertension. Circ Res. 2014; 114:1804–1814. doi:
10.1161/CIRCRESAHA.114.302524 Link | Google Scholar
25. Grassi G, Mark A, Esler M. The sympathetic nervous system

alterations in human hypertension. Circ Res. 2015; 116:976–990.
doi: 10.1161/CIRCRESAHA.116.303604 Link | Google Scholar
26. Mancia G, Masi S, Palatini P, Tsioufis C, Grassi G. Elevated

heart rate and cardiovascular risk in hypertension. J Hypertens.
2021; 39:1060–1069. doi: 10.1097/HJH.0000000000002760
27. Grassi G, Quarti-Trevano F, Seravalle G, Dell’Oro R,

Facchetti R, Mancia G. Association between the European
Society of Cardiology/European Society of Hypertension heart
rate thresholds for cardiovascular risk and neuroadrenergic
markers. Hypertension. 2020; 76:577–582. doi:
10.1161/HYPERTENSIONAHA.120.14804 Link | Google Scholar
28. Esler M, Lambert G, Esler D, Ika Sari C, Guo L, Jennings G.

Evaluation of elevated heart rate as a sympathetic nervous
system biomarker in essential hypertension. J Hypertens. 2020;
38:1488–1495. doi: 10.1097/HJH.0000000000002407
29. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach

A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, et al;
ESC Scientific Document Group. 2021 ESC Guidelines for the
diagnosis and treatment of acute and chronic heart failure. Eur
Heart J. 2021; 42:3599–3726. doi: 10.1093/eurheartj/ehab368
30. Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ,
Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari
R, Lechat P, et al; SENIORS Investigators. Randomized trial to
determine the effect of nebivolol on mortality and cardiovascular
hospital admission in elderly patients with heart failure
(SENIORS). Eur Heart J. 2005; 26:215–225. doi:
10.1093/eurheartj/ehi115 Crossref | Medline | Google Scholar
31. Ambrosio G, Flather MD, Böhm M, Cohen-Solal A, Murrone

A, Mascagni F, Spinucci G, Conti MG, van Veldhuisen DJ, Tavazzi
L, et al. β-blockade with nebivolol for prevention of acute
ischaemic events in elderly patients with heart failure. Heart.
2011; 97:209–214. doi: 10.1136/hrt.2010.207365
32. Kjeldsen SE, von Lueder TG, Smiseth OA, Wachtell K,

Mistry N, Westheim AS, Hopper I, Julius S, Pitt B, Reid CM, et al.
Medical therapies for heart failure with preserved ejection
fraction. Hypertension. 2020; 75:23–32. doi:
10.1161/HYPERTENSIONAHA.119.14057 Link | Google Scholar
33. Massie BM, Carson PE, McMurray JJ, Komajda M,

McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger
C, et al; I-PRESERVE Investigators. Irbesartan in patients with
heart failure and preserved ejection fraction. N Engl J Med.
2008; 359:2456–2467. doi: 10.1056/NEJMoa0805450
34. Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP,

Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, et al;
PARAGON-HF Investigators and Committees. Angiotensin-
neprilysin inhibition in heart failure with preserved ejection
fraction. N Engl J Med. 2019; 381:1609–1620. doi:
35. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E,

Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-
Valenzuela E, et al; EMPEROR-Preserved Trial Investigators.
Empagliflozin in heart failure with a preserved ejection fraction. N
Engl J Med. 2021; 385:1451–1461. doi:
36. Cleland JGF, Bunting KV, Flather MD, Altman DG, Holmes J,
Coats AJS, Manzano L, McMurray JJV, Ruschitzka F, van
Veldhuisen DJ, et al; Beta-blockers in Heart Failure Collaborative
Group. Beta-blockers for heart failure with reduced, mid-range,
and preserved ejection fraction: an individual patient-level
analysis of double-blind randomized trials. Eur Heart J. 2018;
39:26–35. doi: 10.1093/eurheartj/ehx564
37. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E,

Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, et
al; ESC Scientific Document Group. 2019 ESC Guidelines for the
diagnosis and management of chronic coronary syndromes. Eur
Heart J. 2020; 41:407–477. doi: 10.1093/eurheartj/ehz425
38. Norwegian Multicenter Study Group. Timolol-induced

reduction in mortality and reinfarction in patients surviving acute
myocardial infarction. N Engl J Med. 1981; 304:801–807. doi:
10.1056/NEJM198104023041401
39. Hjalmarson A, Elmfeldt D, Herlitz J, Holmberg S, Málek I,

Nyberg G, Rydén L, Swedberg K, Vedin A, Waagstein F, et al;
Effect on mortality of metoprolol in acute myocardial infarction. A
double-blind randomised trial. Lancet. 1981; 2:823–827. doi:
10.1016/s0140-6736(81)91101-6
40. Freis ED. Hemodynamics of hypertension. Physiol Rev.

1960; 40:27–54. doi: 10.1152/physrev.1960.40.1.27
41. Olsen MH, Wachtell K, Meyer C, Hove JD, Palmieri V, Dige-

Petersen H, Rokkedal J, Hesse B, Ibsen H. Association between
vascular dysfunction and reduced myocardial flow reserve in
patients with hypertension: a LIFE substudy. J Hum Hypertens.
2004; 18:445–452. doi: 10.1038/sj.jhh.1001716
42. Sucato V, Testa G, Puglisi S, Evola S, Galassi AR, Novo G.

Myocardial infarction with non-obstructive coronary arteries
(MINOCA): Intracoronary imaging-based diagnosis and
management. J Cardiol. 2021; 77:444–451. doi:
10.1016/j.jjcc.2021.01.001 Crossref | Medline | Google Scholar
43. Leren IS, Saberniak J, Majid E, Haland TF, Edvardsen T,

Haugaa KH. Nadolol decreases the incidence and severity of
ventricular arrhythmias during exercise stress testing compared
with β1-selective β-blockers in patients with catecholaminergic
polymorphic ventricular tachycardia. Heart Rhythm. 2016;
13:433–440. doi: 10.1016/j.hrthm.2015.09.029
44. Kaufman ES, Eckhardt LL, Ackerman MJ, Aziz PF, Behr ER,
Cerrone M, Chung MK, Cutler MJ, Etheridge SP, Krahn AD, et al.
Management of congenital long-QT syndrome: commentary from
the experts. Circ Arrhythm Electrophysiol. 2021; 14:e009726.
doi: 10.1161/CIRCEP.120.009726 Link | Google Scholar
45. Wang M, Peterson DR, Rosero S, McNitt S, Rich DQ,

Seplaki CL, Polonsky B, Goldenberg I, Zareba W. Effectiveness
of implantable cardioverter-defibrillators to reduce mortality in
patients with long QT syndrome. Am Coll Cardiol. 2021;
78:2076–2088. doi: 10.1016/j.jacc.2021.09.017
46. Loncaric F, Nunno L, Mimbrero M, Marciniak M, Fernandes

JF, Tirapu L, Fabijanovic D, Sanchis L, Doltra A, Cikes M, et al.
Basal ventricular septal hypertrophy in systemic hypertension.
Am J Cardiol. 2020; 125:1339–1346. doi:
10.1016/j.amjcard.2020.01.045
47. Anderson JL. Treatment of cardiac myopathies with beta

blockers. What do we know, where do we go from here?
Postgrad Med. 1988; Spec No:104–112.
Medline | Google Scholar
48. Dybro AM, Rasmussen TB, Nielsen RR, Andersen MJ,

Jensen MK, Poulsen SH. randomized trial of metoprolol in
patients with obstructive hypertrophic cardiomyopathy. J Am
Coll Cardiol. 2021; 78:2505–2517. doi:
10.1016/j.jacc.2021.07.065 Crossref | Medline | Google Scholar
49. Fauchier L, Boriani G, de Groot JR, Kreutz R, Rossing P,

Camm AJ. Medical therapies for prevention of cardiovascular
and renal events in patients with atrial fibrillation and diabetes
mellitus. Europace. 2021; 23:1873–1891. doi:
10.1093/europace/euab184 Crossref | Medline | Google Scholar
50. Hansson L, Hedner T, Lund-Johansen P, Kjeldsen SE,

Lindholm LH, Syvertsen JO, Lanke J, de Faire U, Dahlöf B,
Karlberg BE. Randomised trial of effects of calcium antagonists
compared with diuretics and beta-blockers on cardiovascular
morbidity and mortality in hypertension: the Nordic Diltiazem
(NORDIL) study. Lancet. 2000; 356:359–365. doi:
10.1016/s0140-6736(00)02526-5
51. Kjeldsen SE, Syvertsen JO, Hedner T. Cardiac conduction

with diltiazem and beta-blockade combined. A review and report
on cases. Blood Press. 1996; 5:260–263. doi:
10.3109/08037059609078057
52. Diercks DB, Ohman EM. Hypertension with acute coronary

syndrome and heart failure. Ann Emerg Med. 2008; 51(Suppl
3):S34–S36. doi: 10.1016/j.annemergmed.2007.11.012
53. Teng L, Fang J, Zhang Y, Liu X, Qu C, Shen C. Perioperative

baseline β-blockers: an independent protective factor for post-
carotid endarterectomy hypertension. Vascular. 2021; 29:270–
279. doi: 10.1177/1708538120946538
54. Blessberger H, Lewis SR, Pritchard MW, Fawcett LJ,

Domanovits H, Schlager O, Wildner B, Kammler J, Steinwender
C. Perioperative beta-blockers for preventing surgery-related
mortality and morbidity in adults undergoing non-cardiac surgery.
Cochrane Database Syst Rev. 2019; 9:CD013438. doi:
10.1002/14651858.CD013438
55. François B, Cahen R, Gravejat MF, Estrade M. Do beta

blockers prevent pressor responses to mental stress and
physical exercise? Eur Heart J. 1984; 5:348–353. doi:
10.1093/oxfordjournals.eurheartj.a061667
56. Frohlich ED. Beta adrenergic blockade in the circulatory

regulation of hyperkinetic states. Am J Cardiol. 1971; 27:195–
199. doi: 10.1016/0002-9149(71)90258-x
57. Abed H, Ball PA, Wang LX. Diagnosis and management of

postural orthostatic tachycardia syndrome: a brief review. J
Geriatr Cardiol. 2012; 9:61–67. doi:
10.3724/SP.J.1263.2012.00061
58. Benowitz NL, Zevin S, Carlsen S, Wright J, Schambelan M,

Cheitlin M. Orthostatic hypertension due to vascular adrenergic
hypersensitivity. Hypertension. 1996; 28:42–46. doi:
10.1161/01.hyp.28.1.42 Link | Google Scholar
59. Radack K, Deck C. β-Adrenergic blocker therapy does not

worsen intermittent claudication in subjects with peripheral
arterial disease. Arch Intern Med. 1991; 151:1769–1776. doi:
10.1016/0741-5214(93)90757-D
60. Tripathi D, Stanley AJ, Hayes PC, Patch D, Millson C,

Mehrzad H, Austin A, Ferguson JW, Olliff SP, Hudson M, et al;
Clinical Services and Standards Committee of the British Society
of Gastroenterology. U.K. guidelines on the management of
variceal haemorrhage in cirrhotic patients. Gut. 2015; 64:1680–
1704. doi: 10.1136/gutjnl-2015-309262
61. Garovic VD, Dechend R, Easterling T, Karumanchi SA,

McMurtry Baird S, Magee LA, Rana S, Vermunt JV, August P;
American Heart Association Council on Hypertension; Council on
the Kidney in Cardiovascular Disease, Kidney in Heart Disease
Science Committee; Council on Arteriosclerosis, Thrombosis and
Vascular Biology; Council on Lifestyle and Cardiometabolic
Health; Council on Peripheral Vascular Disease; and Stroke
Council. Hypertension in pregnancy: diagnosis, blood pressure
goals, and pharmacotherapy: a scientific statement from the
american heart association. Hypertension. 2022; 79:e21–e41.
doi: 10.1161/HYP.0000000000000208 Link | Google Scholar
62. Whelan A, Izewski J, Berkelhammer C, Walloch J, Kay HH.

Labetalol-induced hepatotoxicity during pregnancy: a case
report. AJP Rep. 2020; 10:e210–e212. doi: 10.1055/s-0040-
1713789 Crossref | Medline | Google Scholar
63. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-

blockade on mortality among high-risk and low-risk patients after
myocardial infarction. N Engl J Med. 1998; 339:489–497. doi:
10.1056/NEJM199808203390801
64. Dransfield MT, Voelker H, Bhatt SP, Brenner K, Casaburi R,

Come CE, Cooper JAD, Criner GJ, Curtis JL, Han MK, et al;
BLOCK COPD Trial Group. Metoprolol for the prevention of acute
exacerbations of COPD. N Engl J Med. 2019; 381:2304–2314.
doi: 10.1056/NEJMoa1908142
65. Yang YL, Xiang ZJ, Yang JH, Wang WJ, Xu ZC, Xiang RL.
Association of β-blocker use with survival and pulmonary
function in patients with chronic obstructive pulmonary and
cardiovascular disease: a systematic review and meta-analysis.
Eur Heart J. 2020; 41:4415–4422. doi:
10.1093/eurheartj/ehaa793 Crossref | Medline | Google Scholar
66. Sharma A, Stan MN. Thyrotoxicosis: diagnosis and

management. Mayo Clin Proc. 2019; 94:1048–1064. doi:
10.1016/j.mayocp.2018.10.011
67. Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB,
Kaplan MM, Segal RL; American Association of Clinical
Endocrinologists. American Association of Clinical
Endocrinologists medical guidelines for clinical practice for the
evaluation and treatment of hyperthyroidism and hypothyroidism.
Endocr Pract. 2002; 8:457–469. Crossref | Google Scholar
68. Makdassi R, Decourcelle PH, Moriniere P, Coevoet B, de

Fremont JF, Kassouf J, Roussel A, Gheerbrand JD, Andrejak M,
Fournier A. Blockers of beta and H2 receptors and secondary
hyperparathyroidism in uraemia. Proc Eur Dial Transplant
Assoc. 1981; 18:642–647. Medline | Google Scholar
69. Danesh A, Gottschalk PCH. Beta-blockers for migraine

prevention: a review article. Curr Treat Options Neurol. 2019;
21:20. doi: 10.1007/s11940-019-0556-3
70. Haubenberger D, Hallett M. Essential tremor. N Engl J Med.

2018; 378:1802–1810. doi: 10.1056/NEJMcp1707928
71. Huber M, Kölzsch M, Stahlmann R, Hofmann W, Bolbrinker

J, Dräger D, Kreutz R. Ophthalmic drugs as part of polypharmacy
in nursing home residents with glaucoma. Drugs Aging. 2013;
30:31–38. doi: 10.1007/s40266-012-0036-x
72. Li T, Lindsley K, Rouse B, Hong H, Shi Q, Friedman DS,

Wormald R, Dickersin K. Comparative effectiveness of first-line
medications for primary open-angle glaucoma: a systematic
review and network meta-analysis. Ophthalmology. 2016;
123:129–140. doi: 10.1016/j.ophtha.2015.09.005
73. Lader M. Beta-adrenoceptor antagonists in

neuropsychiatry: an update. J Clin Psychiatry. 1988; 49:213–
223. Medline | Google Scholar
74. Barnes KP, Rainbow CR. Update on banned substances

2013. Sports Health. 2013; 5:442–447. doi:
10.1177/1941738113478546
75. Das M. Panic disorder: propranolol and behavioural therapy.

Br Med J. 2006; 332:1094. doi: 10.1136/bmj.332.7549.1094
76. Henry M, Fishman JR, Youngner SJ. Propranolol and the

prevention of post-traumatic stress disorder: is it wrong to erase
the “sting” of bad memories? Am J Bioeth. 2007; 7:12–20. doi:
10.1080/15265160701518474
77. Brunet A, Saumier D, Liu A, Streiner DL, Tremblay J, Pitman

RK. Reduction of PTSD symptoms with pre-reactivation
propranolol therapy: a randomized controlled trial. Am J
Psychiatry. 2018; 175:427–433. doi:
10.1176/appi.ajp.2017.17050481
78. Hall ME, Rocco MV, Morgan TM, Hamilton CA, Jordan JH,
Edwards MS, Hall JE, Hundley WG. Beta-blocker use is
associated with higher renal tissue oxygenation in hypertensive
patients suspected of renal artery stenosis. Cardiorenal Med.
2016; 6:261–268. doi: 10.1159/000445302
eLetters
eLetters should relate to an article recently published in the
journal and are not a forum for providing unpublished data.
Comments are reviewed for appropriate use of tone and
language. Comments are not peer-reviewed. Acceptable
comments are posted to the journal website only. Comments are
not published in an issue and are not indexed in PubMed.
Comments should be no longer than 500 words and will only be
posted online. References are limited to 10. Authors of the article
cited in the comment will be invited to reply, as appropriate.
Comments and feedback on AHA/ASA Scientific Statements and

Guidelines should be directed to the AHA/ASA Manuscript
Oversight Committee via its Correspondence page.
Sign In to Submit a Response to This Article
Previous  Back to top Next
AHA Journals
Arteriosclerosis, Thrombosis, and Circ: Cardiovascular Imaging Hypertension
Vascular Biology (ATVB)
Circ: Cardiovascular Journal of the American Heart
Circulation Interventions Association (JAHA)
Hypertension Circ: Arrhythmia and Circ: Cardiovascular Quality & Stroke
Electrophysiology Outcomes
Stroke: Vascular and
Circ: Genomic and Precision Circ: Heart Failure Interventional Neurology
Medicine
Circulation Research AIM: Clinical Cases
Journal Information Subjects Features

About Hypertension All Subjects Best of Hypertension Award
Editorial Board Arrhythmia and Electrophysiology Clinical-Pathological Conferences
Meet the Editors Basic, Translational, and Clinical Research Controversies in Hypertension
Reprints Critical Care and Resuscitation Early Career
Customer Service and Ordering Information Epidemiology, Lifestyle, and Prevention Education and Webinars
AHA Journals RSS Feeds Genetics Featured on the Cover
For International Users Heart Failure and Cardiac Disease Meeting Abstracts
Institutions/Librarians FAQ Hypertension Statements & Guidelines
For Subscribers Imaging and Diagnostic Testing
Subscriber Help Intervention, Surgery, Transplantation Resources & Education

Wolters Kluwer Privacy Policy Quality and Outcomes AHA Guidelines and Statements
Stroke Scientific Councils
Vascular Disease Information for Advertisers
For Authors & Reviewers

Instructions for Authors
Submission Site
AHA Journals EDI Editorial Board
Author Reprints
ABOUT US OUR SITES TAKE ACTION ONLINE COMMUNITIES

About the AHA/ASA  American Heart  Advocate  AFib Support 
Association
Annual Report  Donate  Garden Community 
American Stroke 
AHA Financial Information  Association Planned Giving  Patient Support Network 
Careers  Professional Heart Daily  Volunteer 
SHOP  More Sites 

National Center
7272 Greenville Ave. Latest Heart and Stroke 
Dallas, TX 75231 News
Customer Service AHA/ASA Media Newsroom 

1-800-AHA-USA-1
Global Programs 
1-800-242-8721
Local Info
Contact Us
Follow Us:     
Privacy Policy Copyright Ethics Policy Conflict of Interest Policy Linking Policy Diversity
Careers Suppliers & Providers Accessibility Statement State Fundraising Notices
© American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. The American Heart Association
is qualified 501(c)(3) tax-exempt organization.
*Red Dress ™ DHHS, Go Red ™; AHA; National Wear Red Day ® is registered trademark.
Manage Cookie Preferences

Individualized Beta-Blocker Treatment For High Blood Pressure Dictated by Medical Comorbidities: Ind

Uploaded by

Copyright:

Available Formats

You might also like

Individualized Beta-Blocker Treatment For High Blood Pressure Dictated by Medical Comorbidities: Ind

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Individualized Beta-Blocker Treatment For High Blood Pressure Dictated by Medical Comorbidities: Ind

Uploaded by

Copyright:

Available Formats

ADVERTISEMENT

SCIENCE VOLUNTEER WARNING SIGNS Search  Advanced Search DONATE

Submit your article  

represent an in-homogenous group of drugs and choosing beta-

previous position as first-choice drugs for the treatment of

BP as eﬀectively as all other major antihypertensive drugs.5

These drugs now have been shown to be protective and safe in

Further important advantages of beta-blockers are their favorable

The 2018 Guidelines and Treatment With Beta-Blockers

Table 1. The 2018 ESC/ESH Hypertension Guidelines Mention

Women with childbearing potential/planning pregnancy

Heart rate control (<80 beats/min)

Heart rate (frequency) control

ESC indicates European Society of Cardiology; ESH,

Beta-Blockers and Heart Rate Reduction

Download figure | Download PowerPoint

The Use of Beta-Blocker Treatment in Patients With HF With Mid-

Though no RCT of beta-blocker treatment on composite death

Figure 2 illustrates more in detail the use of beta-blockers in

Download figure | Download PowerPoint

Moreover, a recent individual patient-level analysis of RCTs

Other Cardiac Indications for Beta-Blocker Treatment

Table 2. Other Cardiac Indications for Treatment With Beta-

Acute coronary syndrome

HOCM, subaortic stenosis, septal thickness

Uncontrolled rapid atrial fibrillation combined with diltiazem or verapamil to

Paroxysmal supraventricular arrhythmias, ventricular arrhythmias, other

Post ICD implantation

Attacks of tachycardia after PM implantation for tachy-brady syndrome

CABG indicates coronary artery bypass graft; ICD, implantable

Acute and Chronic Coronary Syndromes

Unspecific Chest Pain, Reduced Coronary Reserve, and

LV Outflow Tract Obstruction

Uncontrolled Rapid Atrial Fibrillation and Combination of Beta-

However, there are patients who do not respond satisfactorily to

One may wonder whether the combination of beta-blocker and

Other Arrhythmias, Cardiac Devices, Palpitations, and Cardiac

Noncardiac Indications for Beta-Blocker Treatment

Table 3. Indication for Beta-Blocker Treatment Related to

Emergency, urgency, and parenteral administration of labetalol

Major noncardiac surgery

Excessive pressor response to exercise and stress

Hyperkinetic heart syndrome

Obstructive sleep apnea syndrome

Peripheral arterial disease with claudication

Portal hypertension, cirrhosis-related oesophageal varices and recurrent

Pregnancy related disorders (eclampsia, preeclampsia)

POTS indicates postural orthostatic tachycardia syndrome.

Emergency, Urgency, and Parenteral Administration of Labetalol

Perioperative Hypertension and Major Noncardiac Surgery

Excessive Pressor Response to Exercise and Mental Stress and

Hyperkinetic heart syndrome may occur in some hypertensive

Postural Orthostatic Tachycardia Syndrome and Orthostatic or

Obstructive Sleep Apnoea Syndrome

Peripheral Arterial Disease with Claudication

Portal Hypertension, Liver Cirrhosis–Related Oesophageal

Pregnancy-Related Disorders (Eclampsia, Preeclampsia)