THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Introduction

HypertensionHypertension (high blood pressure) is one of the major risk factors for cardiovascular

diseases. There is overwhelming evidence that elevated blood pressure (systolic, diastolic or

both) increases the probability of ischemic heart disease, stroke, coronary hem disease and

overall mortality. In the general population, hypertension is more common in males, in

smokers and in older age groups [1]

Arterial Pressure

Arterial blood pressure is generated by the left ventricle ejecting blood into the systemic

vasculature, which acts as a resistance to cardiac output. With each ejection of blood during

ventricular systole, the aortic blood volume increases, which stretches the wall of the aorta.

As the heart relaxes (ventricular diastole), blood flows from the aorta into distributing arteries

that transport the blood to the various organs. Within the organs, the arterial vasculature

undergoes extensive branching and the vessel diameters decrease. The smaller arteries and

arterioles serve as the chief resistance vessels, and through changes in their diameter, serve to

regulate systemic vascular resistance and organ blood flow.

In hemodynamic terms, the mean arterial pressure (MAP) can be described by

Equation 1:   MAP = (CO x SVR) + CVP

where CO = cardiac output, SVR = systemic vascular resistance, and CVP = central venous

pressure. Therefore, increases in CO, SVR or CVP will lead to increases in MAP.

Hypertension Categories

According to the latest U.S. national guidelines (JNC 7 Report), the following categories of

hypertension have been defined:

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THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Classification Systolic(mmHg)

Diastolic(mmHg)

Normal* <120 <80

Prehypertension 120-139 80-89

Stage 1 140-159 90-99

Stage 2 >160 >100

Table 1. Category of Hypertension

*Arterial pressures less than 90/60 mmHg are considered hypotension, and therefore not

normal.

It is important to note that a hypertensive state may defined as an abnormal elevation of either

systolic or diastolic pressure. In past years, the diastolic value was emphasized in determining

whether or not a person was hypertensive.  However, elevations in systolic pressure ("systolic

hypertension") are also associated with increased incidence of coronary and cerebrovascular

disease (e.g., stroke). Therefore, we now recognize that both systolic and diastolic pressure

values are important to note.

Causes of Hypertension

Fig 1. Causes of Hypertension

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There are two basic types of hypertension: primary (essential) hypertension and secondary

hypertension. The vast majority of patients (90-95%) have essential hypertension, which is a

form with no identifiable underlying cause. This form of hypertension is commonly treated

with drugs in addition to lifestyle changes (e.g., exercise, proper nutrition, weight reduction,

stress reduction).

A smaller number of patients (5-10%) have secondary hypertension that is caused by an

identifiable underlying condition such as renal artery disease, thyroid disease, primary

hyperaldosteronism, pregnancy, etc.

BP = blood pressure; CKD = chronic kidney disease; CV = cardiovascular; CVD = cardiovascular disease; DBP = diastolic blood pressure;HT = hypertension; OD = organ damage; RF = risk factor; SBP = systolic blood pressure.

Table 2. Stratification of total CV risk in categories of low, moderate, high and very high risk according to SBP and DBP

Some causes of secondary hypertension are listed below:

Renal artery stenosis

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THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Chronic renal disease Primary hyperaldosteronism Stress Sleep apnea Hyper- or hypothyroidism Pheochromocytoma Preeclampsia Aortic coarctation

Fig 2 Some causes of secondary hypertension

The Pharmacologic Treatment of Systemic Hypertension - Antihypertensive Drugs

Rationale for Pharmacologic Treatment of Hypertension

Patients with primary hypertension are generally treated with drugs that

1) reduce blood volume (which reduces central venous pressure and cardiac output),

2) reduce systemic vascular resistance, or

3) reduce cardiac output by depressing heart rate and stroke volume. Patients with secondary

hypertension are best treated by controlling or removing the underlying disease or

pathology, although they may still require antihypertensive drugs.

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Rationale for Reducing Arterial Pressure

Reduce Cardiac Output

Reduce blood volume

Reduce heart rate

Reduce stroke volume

Reduce Systemic Vascular Resistance

Dilate systemic vasculatureArterial pressure can be reduced by decreasing cardiac output systemic vascular resistance,

or central venous pressure. An effective and inexpensive way of reducing venous pressure

and cardiac output is by using drugs that reduce blood volume. These drugs (diuretics) act on

the kidney to enhance sodium and water excretion. Reducing blood volume not only reduces

central venous pressure, but even more importantly, reduces cardiac output by the Frank-

Starling mechanism due to the reduction in ventricular preload. An added benefit of these

drugs is that they reduce systemic vascular resistance with long-term use.

Fig. 3 Areas of everyday life influenced by hypertension

Many antihypertensive drugs have their primary action on systemic vascular resistance. Some

of these drugs produce vasodilation by interfering with sympathetic adrenergic vascular tone

(sympatholytics) or by blocking the formation of angiotensin II or its vascular receptors.

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THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Other drugs are direct arterial dilators, and some are mixed arterial and venous dilators.

Although less commonly used because of a high incidence of side effects, there are drugs that

act on regions in the brain that control sympathetic autonomic outflow. By reducing

sympathetic efferent activity, centrally acting drugs decrease arterial pressure by decreasing

systemic vascular resistance and cardiac output.

Some antihypertensive drugs, most notably beta-blockers, depress heart rate and contractility

(this decreases stroke volume) by blocking the influence of sympathetic nerves on the heart.

Calcium-channel blockers, especially those that are more cardioselective, also reduce cardiac

output by decreasing heart rate and contractility. Some calcium-channel blockers (most

notably the dihydropyridines) are more selective for the systemic vasculature and therefore

reduce systemic vascular resistance.[2][3]

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Fig. 4 Methods for controlling Hypertension

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Drugs Used to Treat Hypertension

Classes of drugs used in the treatment of hypertension are listed below.  Clicking on the drug

class will link you to the page describing the pharmacology of that drug class.

Diuretics

-  thiazide diuretics

-  loop diuretics

-  potassium-sparing diuretics

 

Vasodilators

-  alpha-adrenoceptor antagonists (alpha-blockers)

-  angiotensin converting enzyme inhibitors (ACE inhibitors)

-  angiotensin receptor blockers (ARBs)

-  calcium-channel blockers

-  direct acting arterial dilators

-  ganglionic blockers

-  nitrodilators

-   potassium-channel openers

-  renin inhibitors

 

Cardioinhibitory drugs

-  beta-blockers

-  calcium-channel blockers

 

Centrally acting sympatholytics

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Table 3. Blood Pressure Levels and Treatment Guidance

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Oral Antihypertensive Drugs

Table 4. Oral Antihypertensive Drugs

Beta-Adrenoceptor Antagonists (Beta-Blockers)

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THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Beta blockers (β-blockers, beta-adrenergic blocking agents, beta antagonists, beta-adrenergic

antagonists, beta-adrenoreceptor antagonists, or beta adrenergic receptor antagonists) are a

class of drugs that target the beta receptor. Beta receptors are found on cells of the heart

muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the

sympathetic nervous system and lead to stress responses, especially when they are stimulated

by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of

epinephrine and other stress hormones, and weaken the effects of stress hormones.

They are particularly used for the management of cardiac arrhythmias, protecting the heart

from a second heart attack (myocardial infarction) after a first heart attack (secondary

prevention),[4] and hypertension.[5]

In 1962, Sir James W. Black found the first clinically significant beta blockers—propranolol

and pronethalol; it revolutionized the medical management of angina pectoris[6] and is

considered by many to be one of the most important contributions to clinical medicine and

pharmacology of the 20th century.[7]

Beta blockers block the action of endogenous catecholamines epinephrine (adrenaline) and

norepinephrine (noradrenaline) in particular, on β-adrenergic receptors, part of the

sympathetic nervous system, which mediates the fight-or-flight response.[8][9] Three types of

beta receptors are known, designated β1, β2 and β3 receptors.[10] β1-adrenergic receptors are

located mainly in the heart and in the kidneys. β2-adrenergic receptors are located mainly in

the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle.[9]

β3-adrenergic receptors are located in fat cells.[11]

General Pharmacology

Beta-blockers are drugs that bind to beta-adrenoceptors and thereby block the binding

of norepinephrine and epinephrine to these receptors. This inhibits normal sympathetic

effects that act through these receptors. Therefore, beta-blockers are sympatholytic drugs.

Some beta-blockers, when they bind to the beta-adrenoceptor, partially activate the receptor

while preventing norepinephrine from binding to the receptor. These partial

agonists therefore provide some "background" of sympathetic activity while preventing

normal and enhanced sympathetic activity. These particular beta-blockers (partial agonists)

are said to possess intrinsic sympathomimetic activity (ISA). Some beta-blockers also possess

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THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

what is referred to as membrane stabilizing activity (MSA).  This effect is similar to the

membrane stabilizing activity ofsodium-channels blockers that represent Class I

antiarrhythmics.

The first generation of beta-blockers were non-selective, meaning that they blocked both

beta-1 (β1) and beta-1 (β2) adrenoceptors. Second generation beta-blockers are more

cardioselective in that they are relatively selective for β1adrenoceptors. Note that this relative

selectivity can be lost at higher drug doses. Finally, the third generation beta-blockers are

drugs that also possess vasodilator actions through blockade of vascular alpha-adrenoceptors.

Fig. 5. General Mechanism of Action of beta blockers

Heart

Beta-blockers bind to beta-adrenoceptors located in cardiac nodal tissue, the conducting

system, and contracting myocytes. The heart has both β1 and β2 adrenoceptors, although the

predominant receptor type in number and function is β1. These receptors primarily bind

norepinephrine that is released from sympathetic adrenergic nerves. Additionally, they bind

norepinephrine and epinephrine that circulate in the blood. Beta-blockers prevent the normal

ligand (norepinephrine or epinephrine) from binding to the beta-adrenoceptor by competing

for the binding site.

Beta-adrenoceptors are coupled to a Gs-proteins, which activate adenylyl cyclase to

form cAMP from ATP. Increased cAMP activates a cAMP-dependent protein kinase (PK-A)

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that phosphorylates L-type calcium channels, which causes increased calcium entry into the

cell. Increased calcium entry during action potentials leads to enhanced release of calcium by

the sarcoplasmic reticulum in the heart; these actions increase inotropy (contractility). Gs-

protein activation also increases heart rate (chronotropy). PK-A also phosphorylates sites on

the sarcoplasmic reticulum, which lead to enhanced release of calcium through the ryanodine

receptors (ryanodine-sensitive, calcium-release channels) associated with the sarcoplasmic

reticulum. This provides more calcium for binding thetroponin-C, which enhances inotropy.

Finally, PK-A can phosphorylate myosin light chains. which may contribute to the positive

inotropic effect of beta-adrenoceptor stimulation.

Because there is generally some level of sympathetic tone on the heart, beta-blockers are able

to reduce sympathetic influences that normally stimulate chronotropy (heart rate), inotropy

(contractility), dromotropy (electrical conduction) and lusitropy (relaxation). Therefore, beta-

blockers cause decreases in heart rate, contractility, conduction velocity, and relaxation rate.

These drugs have an even greater effect when there is elevated sympathetic activity.

Fig. 5. Mechanism of Action of beta blockers

Blood vessels

Vascular smooth muscle has β2-adrenoceptors that are normally activated by norepinephrine

released by sympathetic adrenergic nerves or by circulating epinephrine. These receptors, like

those in the heart, are coupled to a Gs-protein, which stimulates the formation of cAMP.

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Although increased cAMP enhances cardiac myocyte contraction (see above), in vascular

smooth muscle an increase in cAMP leads to smooth muscle relaxation. The reason for this is

that cAMP inhibitsmyosin light chain kinase that is responsible for phosphorylating smooth

muscle myosin. Therefore, increases in intracellular cAMP caused by β2-agonists inhibits

myosin light chain kinase thereby producing less contractile force (i.e., promoting

relaxation).

Compared to their effects in the heart, beta-blockers have relatively little vascular effect

because β2-adrenoceptors have only a small modulatory role on basal vascular tone.

Nevertheless, blockade of β2-adrenoceptors is associated with a small degree of

vasoconstriction in many vascular beds. This occurs because beta-blockers remove a small

β2-adrenoceptor vasodilator influence that is normally opposing the more dominant alpha-

adrenoceptor mediated vasoconstrictor influence.

Therapeutic Indications

Beta-Blockers

Cardiac Effects

Decrease contractility

(negative intropy)

Decrease relaxation rate

(negative lusitropy)

Decrease heart rate

(negative chronotropy)

Decrease conduction velocity

(negative dromotropy)

Vascular Effects

Smooth muscle contraction

(mild vasoconstriction)

Beta-blockers are used for treating hypertension, angina, myocardial infarction, arrhythmias

and heart failure.

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Hypertension

Beta-blockers decrease arterial blood pressure by reducing cardiac output. Many forms of

hypertension are associated with an increase in blood volume and cardiac output. Therefore,

reducing cardiac output by beta-blockade can be an effective treatment for hypertension,

especially when used in conjunction with adiuretic. Acute treatment with a beta-blocker is not

very effective in reducing arterial pressure because of a compensatory increase in systemic

vascular resistance. This may occur because of baroreceptor reflexes working in conjunction

with the removal of β2 vasodilatory influences that normally offset, to a small degree, alpha-

adrenergic mediated vascular tone. Chronic treatment with beta-blockers lowers arterial

pressure more than acute treatment possibly because of reduced renin release and effects of

beta-blockade on central and peripheral nervous systems. Beta-blockers have an additional

benefit as a treatment for hypertension in that they inhibit the release of renin by the kidneys

(the release of which is partly regulated by β1-adrenoceptors in the kidney). Decreasing

circulating plasma renin leads to a decrease in angiotensin II and aldosterone, which enhances

renal loss of sodium and water and further diminishes arterial pressure.

Hypertension in some patients is caused by emotional stress, which causes enhanced

sympathetic activity. Beta-blockers can be very effective in these patients.

Beta-blockers are used in the preoperative management of hypertension caused by a

pheochromocytoma, which results in elevated circulating catecholamines. When used for this

condition, the blood pressure is first controlled using an alpha-blocker such

as phenoxybenzamine, and then a beta-blocker can be carefully administered to reduce the

excessive cardiac stimulation by the catecholamines. It is important that a beta-blocker is

administered only after adequate blockade of vascular alpha-adrenoceptors so that a

hypertensive crisis does not occur as a result of unopposed alpha-adrenoceptor stimulation.

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A-V, atrio-ventricular; eGFR, estimated glomerular filtration rate; LV, left ventricular.

Table 5. Compelling and possible contra-indications to the use of antihypertensive

drugs

Theraputic Use of Beta-Blockers

Hypertension Angina Myocardial infarction Arrhythmias Heart failure

The antianginal effects of beta-blockers are attributed to their cardiodepressant and

hypotensive actions. By reducing heart rate, contractility, and arterial pressure, beta-blockers

reduce the work of the heart and the oxygen demand of the heart. Reducing oxygen demand

improves the oxygen supply/demand ratio, which can relieve a patient of anginal pain that is

caused by a reduction in the oxygen supply/demand ratio due to coronary artery disease.

Furthermore, beta-blockers have been found to be very important in the treatment of

myocardial infarction in that they have been shown to decrease mortality. Their benefit is

derived not only from improving the oxygen supply/demand ratio and reducing arrhythmias,

but also from their ability to inhibit subsequent cardiac remodeling.

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Arrhythmias

The antiarrhythmic properties beta-blockers (Class II antiarrhythmic) are related to their

ability to inhibit sympathetic influences on cardiac electrical activity. Sympathetic nerves

increase sinoatrial node automaticity by increasing the pacemaker currents, which increases

sinus rate.  Sympathetic activation also increases conduction velocity (particularly at the

atrioventricular node), and stimulates aberrant pacemaker activity (ectopic foci). These

sympathetic influences are mediated primarily through β1-adrenoceptors. Therefore, beta-

blockers can attenuate these sympathetic effects and thereby decrease sinus rate, decrease

conduction velocity (which can block reentry mechanisms), and inhibit aberrant pacemaker

activity. Beta-blockers also affect non-pacemaker action potentials by increasing action

potential duration and the effective refractory period. This effect can play a major role in

blocking arrhythmias caused by reentry.

Heart failure

The majority of patients in heart failure have a form that is called systolic dysfunction, which

means that the contractile function of the heart is depressed (loss of inotropy). Although it

seems counterintuitive that cardioinhibitory drugs such as beta-blockers would be used in

cases of systolic dysfunction, clinical studies have shown quite conclusively that some

specific beta-blockers actually improve cardiac function and reduce mortality. Furthermore,

they have been shown to reduce deleterious cardiac remodeling that occurs in chronic heart

failure. Although the exact mechanism by which beta-blockers confer their benefit to heart

failure patients is poorly understood, it may be related to blockade of excessive, chronic

sympathetic influences on the heart, which are known to be harmful to the failing heart.

Different Classes of Beta-Blockers and Specific Drugs

Beta-blockers that are used clinically can be divided into two classes: 1) non-selective

blockers (block both β1and β2receptors), or 2) relatively selective

β1 blockers ("cardioselective" beta-blockers). Some beta-blockers have additional

mechanisms besides beta-blockade that contribute to their unique pharmacologic profile. The

two classes of beta-blockers along with specific compounds are listed in the following table.

Additional details for each drug may be found at www.rxlist.com. The clinical uses indicated

in the table represent both on and off-label uses of beta-blockers. For example, a given beta-

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blocker may only be approved by the FDA for treatment of hypertension; however,

physicians sometimes elect to prescribe the drug for angina because of the class-action

benefit that beta-blockers have for angina.

Clinical Uses

Class/Drug HTN

Angina

Arrhy

MI

CHF Comments

Non-selective β1/β2

carteolol X ISA; long acting; also used for glaucoma

carvedilol X X α-blocking activity

labetalol X X ISA; α-blocking activity

Nadolol X X X X long acting

penbutolol X X ISA

pindolol X X ISA; MSA

propranolol X X X X MSA; prototypical beta-blocker

Sotalol X several other significant mechanisms

Timolol X X X X primarily used for glaucoma

β1-selective

acebutolol X X X ISA

Atenolol X X X X

betaxolol X X X MSA

bisoprolol X X X

Esmolol X X ultra short acting; intra or postoperative HTN

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metoprolol X X X X X MSA

nebivolol X         relatively selective in most patients; vasodilating (NO release)

Abbreviations: HTN, hypertension; Arrhy, arrhythmias; MI, myocardial infarction; CHF, congestive heart failure; ISA, intrinsic sympathomimetic activity.

Table 6. Clinical uses of different class of beta blockers

Side Effects and Contraindications

Cardiovascular side effects

Many of the side effects of beta-blockers are related to their cardiac mechanisms and include

bradycardia, reduced exercise capacity, heart failure, hypotension, and atrioventicular (AV)

nodal conduction block. Beta-blockers are therefore contraindicated in patients with sinus

bradycardia and partial AV block. The side effects listed above result from excessive

blockade of normal sympathetic influences on the heart. Considerable care needs to be

exercised if a beta-blocker is given in conjunction with cardiac selective calcium-channel

blockers (e.g., verapamil) because of their additive effects in producing electrical and

mechanical depression. Although this may change with future clinical trials on safety and

efficacy of beta-blockers in heart failure, at present only carvedilol and metoprolol have been

approved by the FDA for this indication.

Other side effects

Bronchoconstriction can occur, especially when non-selective beta-blockers are administered

to asthmatic patients. Therefore, non-selective beta-blockers are contraindicated in patients

with asthma or chronic obstructive pulmonary disease. Bronchoconstriction occurs because

sympathetic nerves innervating the bronchioles normally activate β2-adrenoceptors that

promote bronchodilation. Beta-blockers can also mask the tachycardia that serves as a

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warning sign for insulin-induced hypoglycemia in diabetic patients; therefore, beta-blockers

should be used cautiously in diabetics.

Review of Literature

Should beta blockers remain first-line drugs for hypertension?-Maros Elsik et

al.,

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Hypertension is an important risk factor for stroke and other cardiovascular events.

National and international guidelines recognise five classes of drugs for the first-line

treatment of hypertension, but the effectiveness of beta blockers has recently been

questioned, especially in the elderly. However, achieving a lower blood pressure is

more important than the choice of drug used in treatment. Many patients will need

more than one drug to treat their hypertension. Beta blockers remain important and

effective drugs, but age and comorbidities need to be considered when selecting a

first-line drug.[12]

Beta-Blockers in the Treatment of Hypertension: Latest Data and Opinions-

Danai Tsalta et al.,

Beta-adrenergic blockers have been widely used as first-line drugs in the treatment of

idiopathic arterial hypertension for around 40 years. Recent meta-analyses, however,

suggest that they are significantly inferior to other categories of drugs (thiazide

diuretics, calcium channel blockers, angiotensin converting enzyme [ACE] inhibitors,

angiotensin II receptor blockers). This observation has led to the demotion of beta-

blockers to fourth-line drugs in the latest guidelines of the British Hypertension

Society.3 The aim of this review is to illuminate the historical course of the use of

beta-blockers in the treatment of hypertension up to the present day, to present the

most recent data from meta-analyses that have downgraded them from

antihypertensive drugs of first choice, and to discuss the different views expressed in

the most recent guidelines for the treatment of hypertension issued by the European

Society of Hypertension and the European Society of Cardiology.[13]

Current and Future Status of Beta-blockers in the Treatment of Hypertension-

Steven G. Chrysant- et al.,

Beta-adrenergic receptor blockers (beta-blockers) are effective and safe

antihypertensive drugs, and have been recommended as first-line therapy for

hypertension by all Joint National Committees (JNCs) for the prevention, detection,

evaluation, and treatment of high blood pressure (BP) from the first to the last (JNC-

7) in 2003. However, recently questions have been raised by several investigators

regarding the antihypertensive effectiveness and safety of these drugs. The Medline

literature on this subject was searched and pertinent studies were retrieved. Other

pertinent references from existing publications were retrieved and analyzed up to

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2007. Additionally, a historical perspective on the discovery of beta-blockers and

their mechanism of action is given. Most of the reviewed short-term and long-term

clinical trials demonstrate an effective and safe antihypertensive pattern for the beta-

blockers. The weaknesses identified include the adverse effect of older beta-blockers

on glucose control and stroke protection, especially in older persons. These adverse

effects are attributed to their mechanism of action and BP effectiveness. On the basis

of the evidence presented, beta-blockers are effective and safe antihypertensive drugs

and should still be recommended as first-line therapy in most uncomplicated

hypertensive patients, either alone or in combination with other drugs. There are

reservations regarding their administration to diabetic and older hypertensive patients.

However, when compelling indications for their use exist, they should not be

withheld.[14]

Beta blockers and their combinations in the management of hypertension-Ker

JA,

Beta blockers should not be used as first-line monotherapy for the treatment of

hypertension, but can be added at a later stage as a fourth-line drug to control

pressure. There are still compelling indications for the use of beta blockers.[15]

Beta-blockers as Single-Agent Therapy for Hypertension and the Risk of

Mortality among Patients with Chronic Obstructive Pulmonary Disease-David

H. Au et al.,

Compared with calcium channel blockers, betablockers were associated with a

decrease in mortality from any cause after adjusting for propensity for having been

prescribed a beta-blocker (hazard ratio _ 0.57; 95% confidence interval: 0.33 to 0.89).

The association was similar when beta-blockers were compared with all other

antihypertensive medications, and the decreased risk of mortality was apparent among

patients with pre-existing cardiac disease. Restriction of analyses to long-acting

calcium channel blockers or to patients who used beta-agonists did not affect the point

estimates. Exposure to the remaining classes of antihypertensive agents was not

associated with mortality.[16]

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THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

Effect of Obesity on the Traditional and Emerging Cardiovascular Disease Risk

Factors in African American Women-Queen Obiageli Henry-Okafor

Obesity is a growing health care concern with cardiovascular disease (CVD)

implications. African American women (AAW) have the highest prevalence rate of

obesity and highest CVD morbidity and mortality rate of all ethnic groups. The

traditional CVD risk factors have not been sufficient to explain this disparity in

disease prevalence and outcomes. Current knowledge is limited regarding the

interaction between various levels of adiposity and both traditional and emerging

CVD risk factors, particularly in AAW. This study sought to explore these

interactions.[17]

Atenolol & Beta-blockers for primary hypertension: Do they perform under

pressure?- G Michael Allan & Christina Korownyk

Atenolol is an inferior choice for blood pressure treatment. Beta-blockers in general

should not be considered first line in age ≥60 and some have suggested they should

not be first line in any patient with uncomplicated hypertension.[18]

Assessment of Clinical Pharmacist Management of Lipid-Lowering Therapy in a

Primary Care Setting- Traywick Till et. al.,

Pharmacists have been shown to positively impact the outcomes of care for treatment

of many different kinds of disease states. In particular, pharmacist-run lipid clinics

have enjoyed varying degrees of success, depending on the outcome assessed. At our

hospital, when a patient is transferred to the pharmacist coordinated lipid clinic, the

primary care pharmacist is responsible for ordering and interpreting labs and

prescribing and monitoring lipid-altering therapy. [19]

How strong is the evidence for use of beta-blockers as first-line therapy for

hypertension? Systematic review and meta-analysis- Hazel A. Bradley

Beta-blockers are inferior to CCBs and to RAS inhibitors for reducing several

important hard end points. Compared with diuretics, they had similar outcomes, but

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THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

were less well tolerated. Hence beta-blockers are generally suboptimal first-line

antihypertensive drugs.[20]

Why β-Blockers Should Not Be Used as First Choice in Uncomplicated

Hypertension-Alberto Ranieri De Caterina, and Antonio Maria Leone

In the past 4 decades, _ blockers (BBs) have been widely used in the treatment of

uncomplicated hypertension and are still recommended as first-line agents in national

and international guidelines. Their putative cardioprotective properties, however,

derive from the extrapolation into primary prevention of data relative to the reduction

of mortality observed in the 1970s in patients with previous myocardial infarctions.

In the past 5 years, a critical reanalysis of older trials, together with several meta-

analyses, has shown that in patients with uncomplicated hypertension BBs exert a

relatively weak effect in reducing stroke compared to placebo or no treatment, do not

have any protective effect with regard to coronary artery disease and, compared to

other drugs, such as calcium channel blockers, renin-angiotensin-aldosterone system

inhibitors or thiazide diuretics, show evidence of worse outcomes, particularly with

regard to stroke. Several reasons can explain their reduced cardioprotection: their

suboptimal effect in lowering blood pressure compared to other drugs; their “pseudo

antihypertensive” efficacy (failure to lower central aortic pressure); their undesirable

adverse effects, which reduce patients’ compliance; their unfavourable metabolic

effects; their lack of an effect on regression of left ventricular hypertrophy and

endothelial dysfunction. In conclusion, the available evidence does not support the

use of BBs as first-line drugs in the treatment of hypertension. Whether newer BBs,

such as nebivolol and carvedilol, which show vasodilatory properties and a more

favorable hemodynamic and metabolic profile, will be more efficacious in reducing

morbidity and mortality remains to be determined.[21]

Hypertension Guidelines-Jeffery Martin

An estimated 73 million people in the United States live with hypertension. As many

as 55,000 deaths are directly attributed to hypertension each year, and it is considered

an underlying or contributing factor in at least another 300,000. In 2003, the Joint

National Committee on Prevention, Detection, Evaluation, and Treatment of High

Blood Pressure (JNC) issued its seventh report, which provided guidelines for the

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 24

THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

diagnosis and management of this disease. Included in the guidelines were: a new

classifi cation system for hypertension; recommendations for lifestyle modifi cations;

and recommendations for pharmacologic therapy. New JNC guidelines are expected

in 2009, but until then, and to understand the forthcoming changes in

recommendations, it is important to revisit and review those of JNC 7.[22]

β-Adrenergic Receptor Blockers and Weight Gain-A Systematic Analysis- Arya

M. Sharma et. al.,

One of the arguments put forward against the primary use of b-blockers has been

concern about adverse metabolic effects, such as unfavorable effects on lipids or

insulin sensitivity. Another less-appreciated potential drawback is their propensity to

cause weight gain in some patients. In 8 evaluable prospective randomized controlled

trials that lasted $6 months, body weight was higher in the b-blocker than in the

control group at the end of the study. The median difference in body weight was 1.2

kg (range 20.4 to 3.5 kg). A regression analysis suggested that b-blockers were

associated with an initial weight gain during the first few months. Thereafter, no

further weight gain compared with controls was apparent. There was no relationship

between demographic characteristics and changes in body weight. Based on these

observations, the first-line use of b-blockers in obese hypertensive patients should be

reviewed. Obesity management in overweight hypertensive patients may be more

difficult in the face of b-blocker treatment.[23]

How strong is the evidence for use of beta-blockers as first-line therapy for

hypertension? Systematic review and meta-analysis-Hazel A. Bradley

Beta-blockers are inferior to Calcium Channel Blocker (CCBs) and to Renin

Angiotensin System (RAS) inhibitors for reducing several important hard end points.

Compared with diuretics, they had similar outcomes, but were less well tolerated.

Hence beta-blockers are generally suboptimal first-line antihypertensive drugs.[24]

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Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 27

THE EFFICACY OF BETA-BLOCKERS FOR THE TREATMENT OF HYPERTENSION

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Systematic Analysis, 37: 250-254.

24. Hazel A. Bradley et al., (2006), How strong is the evidence for use of beta-blockers as

first-line therapy for hypertension? Systematic review and meta-analysis, Journal of

Hypertension, 2006, 24:2131–2141

Shree Dev Bhoomi Institute of Education, Science and Technology, Dehradun 28