Right Beta Blockers for the Right Patientsperkicabangmalang.org/assets/files/4. Right Beta... · Right Beta Blockers for the Right Patients JOHN DOE, MD SUBTITLE 32 PT ARIAL BOLD

Right Beta Blockers

for the Right Patients

JOHN DOE, MD

SUBTITLE 32 PT ARIAL BOLD ITALICS

Indra Prasetya

Department of Cardiology and Vascular Medicine,Faculty of Medicine Brawijaya University,

Saiful Anwar General Hospital,Malang

DISCLOSURE STATEMENT OF

FINANCIAL INTEREST

• Nothing To Disclose

2003: BB become the most controversial

antiHTNs!!

1980: BB become the most popular antiHTNs after

diuretics. Practolol – First β1 selective.

1963: Therapeutic breakthrough, Propronolol

introduced by J.W.Black

1948: Ahlquist classified adrenergic receptors into α

and β receptors.

1958: Dichloroisoprenaline (DCI) – First BB

•2019: ??????

History

Cardiovascular disease continuum:

From risk factors to irreversible damage

Cardiovascular disease continuum:

The role of sympathetic overdrive

Sympathetic overdrive

Autonomous nervous system –

silent regulator of all bodily functions

Autonomous nervous system –

silent regulator of all bodily functions

Parasympathetic system "rest and digest"

Sympathetic system"fight or flight" "

How to measure activity of sympathetic system

in humans?

• Sympathetic adrenergic neuroimaging• Microneurography• Regional and total norepinephrine spillover• Plasma norepinephrine• Power spectral analysis of heart rate• Heart rate

SYMPATHETIC OVERDRIVE – AN IMPORTANT

RISK FACTOR FOR HYPERTENSION AND

CARDIOVASCULAR COMPLICATIONS

PRESENTING WITH ELEVATED HEART RATE

Dyer AR, et al.: Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies. Am J Epidemiol1980, 112:736–749

Heart rate is associated with mortality

Chicago People Gas Company study, n=1233, 40–59

years

CRUSADE quality improvement initiative. Eur Heart J 2010;31:552–560.

Elevated Heart Rate is a Risk Factor in patients with Heart Disease

CRUSADE Registry (n = 135 164)

Inverse linear relation between RHR and life

expectancy in mammals and humans

Cook S et al. Eur Heart J 2006;27:2387-2393

Heart rate = 25/min

Life span = ?

Heart rate = 25/min

Life span = 150 years

SYMPATHETIC OVERDRIVE IS

COMMON AT INITIAL STAGE OF

HYPERTENSION

Jia Hu, MMa, et al. Association of elevated resting pulse rate with increased risk of hypertension development in children. A prospective study in Suzhou, China. Medicine (2017) 96:32(e7696)

Elevated resting heart rate predicts development of

hypertension in children. Suzhou Study

Jia Hu, MMa, et al. Association of elevated resting pulse rate with increased risk of hypertension development in children. A prospective study in Suzhou, China. Medicine (2017) 96:32(e7696)

Every 10bpm increase in heart rate was associated with a 26% greater risk of hypertension development in boys

Elevated resting heart rate predicts development of

hypertension in children. Suzhou Study

Peter M. Okin et al. All-cause and cardiovascular mortality in relations to changing heart rate during treatment of hypertensive patients with electrocardiographic left ventricular hypertrophy. European Heart Journal (2010) 31, 2271–2279

Heart rate ≥ 84 bpm is associated with increased mortality

LIFE Study

In most studies of hypertension, HR was considered to be elevated when it was higher than 80–85 bpm

Symptomatic tachycardia HR reduction by available drugs (mostly beta-1 selective beta-blockers) should be considered

Tachycardia is frequent alsoin established hypertension (n=38,145)

Heart rate (bpm)

0

5

10

15

20

25

1.43.7

8.0

13.9

19.420.8

0.9 0.5 0.5

% P

atie

nts

<55 55-60

60-65

65-70

70-75

75-80

100-105

105-110

>110

14.5

9.6

4.32.6

80-85

85-90

90-95

95-100

Farinaro E et al, Nutr Metab Cardiovasc Dis 1999:9;196

30%

Julius S, Pascual AV, London R. Role of parasympathetic inhibition in the hyperkinetic type of borderline hypertension. Circulation. 1971; 44: 413-8.

Borderline hypertensives present exagerated response to

beta-blockers as compared to normotensives

M Wofford et al. Antihypertensive Effect of a- and b-Adrenergic Blockade in Obese and Lean Hypertensive Subjects. AJH 2001; 14:694–698.

Blood pressure is more sensitive to adrenergic blockade

in obese than in lean hypertensive patients

BETA-BLOCKERS REDUCE

SYMPATHETIC OVERDRIVE IN

HYPERTENSION WITH CLINICAL

BENEFITS

Inhibition of sympathetic overdrive

Alpha2-agonists(moxonidine)

Beta-blockers

Alpha-blockers

Ganglion-blocking drugs(trimetaphane)

Beta-Adrenergic Blockers

Alpha-1

• Vasoconstriction

• Increased peripheral

resistance

• Increased blood pressure

Alpha-2

• Inhibition of norepinepherine

release

• Inhibition of insulin release

Beta-Blockers

Beta-1

• Tachycardia

• Increased lipolysis

• Increased

myocardial

contractility

Beta-2

• Vasodilation (in skeletal vasculature)

• Slightly decreased peripheral

resistance

• Bronchodilation

• Increased muscle and liver

glycogenolysis

• Increased release of glucagon

Properties

Receptor Blockade

Nonselective β blockade

Selective β1 blockade

β+α blockade

Intrinsic sympathomimetic property-ISA

(partial agonistic action)

Membrane stabilising action-MSA

(Local anaesthetic action-Na channel block)

Classification

Properties of β1 Selectivity

Less broncho constriction

Less interference with CHO metabolism less hypoglycemia preferred in diabetics

Less chances of Raynaud's phenomenon

Less deleterious effect on blood lipid profile

Less impairment of exercisecapacity

Less effect on tremor

Properties of ISA

(Intrinsic Sympathomimetic Activity)

Less bradycardia

Less rebound effect on withdrawal

Less deleterious effect on blood lipid profile

Not effective in migraine prophylaxis

Not suitable for secondary prophylaxis of MI

3rd Generation AgentsDrug MSA ISA Beta blockade Other properties

Labetalol Non selective α1 blockade

Carvedilol

+ +

+ Non selective α1 blockade,CCB

Antioxidant

Bucindolol + Non selective α1 blockade,β2,β3 agonism

Increases HDL cholesterol

Celiprolol + β1 selective β2 agonism

NO release

Nebivolol β1 selective •NO release

•Inhibits platelet aggregation

Bevantolol Nonselective α1 blockade

CCB

USES

CARDIOVASCULAR

Hypertension

Angina

Myocardial infarction

Arrhythmia

Cardiomyopathy

CCF

Dissecting aneurysm of aorta

NON - CARDIOVASCULAR

Thyrotoxicosis

Pheochromocytoma

Migraine prophylaxis

Essential tremor

Glaucoma

Anxiety

Portal hypertension

Anti psychotic induced

akathisia

Acute coronary syndrome

• Beta-blockers reduce mortality and reinfarction by 20-25% in those who

have recovered from an infarction [1].

• Oral treatment with beta-blockers should be considered for all ST-

elevation myocardial infarction (STEMI) patients without contraindications

(Class IIa, Level B) [2]. They are indicated if STEMI patients also have

heart failure or LV dysfunction (Class I, Level A) [2].

[1] De Sutter J, Mendes M, Franco OH. Chapter 19 Cardioprotective drugs. In: Gielen S, De Backer G, Piepoli MF, Wood D, editors. The

ESC Textbook of Preventive Cardiology. 2nd ed. United Kingdom: Oxford University Press, 2016.

[2] Steg G, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-

segment elevation. Eur Heart J 2012; 33: 2569–2619.

Stable coronary artery disease

• Beta-blockade is a very effective symptomatic treatment, alone or

combined with another drug, for most of patients with classical angina [1].

• Beta-blockers and/or calcium channel blockers are first-line treatment to

control heart rate and anginal symptoms (Class I, Level A) [3].



Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease. Eur Heart J

2013; 34: 2949–3003.

Heart Failure

• Beta-blockers have been shown to reduce mortality and heart failure

readmissions in patients with heart failure with a reduced ejection fraction

(HFrEF) [1].

• Beta-blockers are recommended, in addition to ACE inhibitors, for patients

with stable, symptomatic HFrEF (Class I, Level A) [4].

• Bisoprolol, Carvedilol, Metoprolol and Nebivolol are licensed for use in

HFrEF and should be preferred [4].



[4] Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. The

Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J

2016; 37: 2129-2200.

Arrhythmia

• Beta-blockers can be used to slow the heart rate in patients with

arrhythmias such as atrial flutter and/or atrial fibrillation [1].

• They are effective in the control of ventricular arrhythmias related to

sympathetic activation, acute coronary syndrome, and heart failure;

including the prevention of sudden cardiac death [1].



Contraindications and side effects• The most frequent side effects of beta-blockers include: hypotension, bradycardia,

bronchospasm, cold extremities, fatigue, headache, sleep disturbances and increased

insulin resistance [1].

• High-degree AV block is an absolute contraindication (if no pacemaker) [1].

• Use cardioselective beta-blockers in case of chronic obstructive pulmonary disease

(COPD); start low and go slow [1].

• Asthma is a relative contraindication for the use of beta-blockers [4]. These drugs

should be used with caution and preferably with specialist advice.



[4] Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. The

Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J

2016; 37: 2129-2200.

Take Home Message Beta-blockers are a diverse group of medicines and prescribers should consider their different

properties, along with the presence of co-morbidities, to individualise care for patients with

cardiovascular conditions

When a beta-blocker is initiated, a slow upwards titration of dose is recommended to minimise

adverse effects. Beta-blockers should also be withdrawn slowly, ideally over several months, to

prevent rebound symptoms such as resting tachycardia.

Beta receptor selectivity enhances the beneficial effects of beta blockers and allows treatment

of patients with co-morbidities

New generation of Beta Blocker : β1 selective, NO production, anti oxidative properties.

THANK YOU

BACKUP SLIDES

Treatment strategies and choice of drugs

2013 ESH/ESC Hypertension Guidelines

Drugs to be preferred in specific conditions

2013 ESH/ESC Hypertension Guidelines

Wald and Law. BMJ 2009; b1665

Superior blood pressure and heart rate control with

bisoprolol ADLIB Trial (n=25, age 28 – 55 years)

Deary AJ, et al. Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs. J Hypertens. 2002; 20: 771-7.

60

65

70

80

100

110

120

140

130

90

150

160M

ean

BP

(m

m H

g)

Mean

HR

(/m

in)

Bisoprolol and nebivolol: Blood pressure loweringNEBIS trial

Czuriga I et al.. Comparison of the new cardioselective beta-blocker nebivolol with bisoprolol in hypertension: The nebivolol,

bisoprolol multicenter study (NEBIS). Cardiovascular Drugs and therapy 2003: 17: 257-63

5 mg nebivolol

5 mg bisoprolol

Cardiovascular disease continuum: The role of sympathetic overdrive


Arne H. Strand et al. Arterial plasma noradrenaline predicts left ventricular mass independently of blood pressure and body build in men who develop hypertension over 20 years. J Hypertens 2006; 24:905–913

Increased plasma levels of adrenaline predict development of left ventricular hypertrophyTwenty-year follow-up

1984 2004



Reduction of atherosclerosis during beta-blocker therapy

BCAPS

ELVA

Circulation; 104:1477-1482, 2001.

Risk of plaque rupture triples in patients with tachycardia



Cardiac remodeling: mechanism behind heart failure

Acute myocardialinfarction

Hours - days

Expansion of hypokineticsegment, thining of heart wall

Days - months

Continues remodeling

Jessup i wsp. N Engl J Med. 2003;348:2007-2018

Necrosis Necrosis

Sympathetic system in heart failure

• Sympathetic overactivity

• Decreased cardiac neuronal density

• Reduced beta-receptor density

• Aggrevated norepinephrine release

Inhibition of sympathetic overdrive

Alpha2-agonists(moxonidine)

Beta-blockers

Alpha-blockers

Ganglion-blocking drugs(trimetaphane)

Cohn JN, et al MOXCON Investigators. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail. 2003; 5: 659-67

Higher mortality in heart failure patients treatedwith moxonidine …MOXCON trial

♂

Cohn JN, et al MOXCON Investigators. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail. 2003; 5: 659-67

…despite lower plasma norepinehprine concentrationMOXCON trial

Carvedilol(n=696)

Placebo(n=398)

Survival

0 50 100 150 200 250 300 350 400

1.0

0.9

0.8

0.7

0.6

0.5

RRR = 35%p<0.001

Packer et al (1996)

Lancet (1999)

0 200 400 600 800

1.0

0.8

0.6

0

Bisoprolol(n=1327)

Placebo(n=1320)

p<0.0001

Survival

RRR = 34%

The MERIT-HF Study Group (1999)

Months

Śmiertelność %

0 3 6 9 12 15 18 21

20

15

10

5

0

Placebo(n=1496)

Metoprolol CR/XL(n=1495)

p=0.0062

RRR = 34%

US Carvedilol Study

Beta-blockers reduce mortality in heartfailure due to systolic dysfunction

CIBIS-II MERIT-HF

Days

Days

No reduction in mortality in patients with heart failuretreated with bucindololBEST trial

A Trial Of The Beta-blocker Bucindolol In Patients With Advanced Chronic Heart Failure. The Beta-blocker Evaluation Of Survival Trial Investigators. N Engl J Med 2001;344:1659-67

No reduction in mortality in patients with heart failuretreated with nebivololSENIORS trial

MD Flather et al. Randomized trial to determine the effect of nebivvolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS) Eur Heart J 2005; 26: 215

Cardiovascular disease continuum: How can we stop it?

The Impact Of Sympathetic Overdrive In The Cardiovascular Continuum

• Sympathetic overdive initiates and acceleratescardiovascular continuum

• Heart rate is a sensitive marker of sympatheticoverdrive

• Only cardioselective beta-blockers safely reducesympathetic overdrive with clinical benefits

Heart rate

Contractility

Blood pressure

Less bronchocontriction

Less metabolic effects

Less circulatory side effects

NONSELECTIVE( b1 b2 )

Similar cardiac and nearly similar antihypertensive effects

More marked pulmonary and peripheral effects

Advantages of selective b1-receptor blockade

Smith C,Teitler M. Cardiovasc Drugs Ther 1999;13:123–126

19.6

7.5

6.0 5.7

0.6 0.3

0

2

4

6

8

10

12

14

16

18

20

β2/β

1sele

ctivity r

atio

Bisoprolol Metoprolol CarvedilolBetaxolol Atenolol Propranolol

Bisoprolol: β2/β1 Selectivity Ratio

at Human β-receptors In Vitro

Concor :Setting Standards

Leopold G. J Cardiovasc Pharmacol. 1986;8(Suppl 11): S16-20. Leopold G, Kutz K. Rev Contemp Pharmacother. 1997;8:35-43.

Bisoprolol needs no dose adjustment in patients with

mild to moderate, Renal or Hepatic dysfunction

Plasma concentration profiles after administration of metoprolol

succinate CR and bisoprolol (3/12 subjects were CYP2D6 “poor” metabolizer)

Metoprolol succinate Bisoprolol

Individual plasma concentration profiles of metoprolol and bisoprolol after single administration of one

metoprolol 100 mg controlled release tablet and one bisoprolol 10 mg normal release tablet

BETA-BLOCKERS AND ASTHMA, COPD

Chest; Jan 2003; 123, 1;

J. W. J. Lammers, H. Th. M. Folgering, C. k A. van Herwaarden Ventilatory Effects of Betal-Receptor-Selective Blockade with Bisoprolol and Metoprolol in Asthmatic Patients. Eur J Clin Pharmacol (1984) 27:141-145

Beta-blockers in COPD patients: Reduced mortality

Placebo Bisoprolol 10 mg Bisoprolol 20 mg Metoprolol 100 mg

Frans H. Rutten, Nicolaas P. A. Zuithoff, Eelko Hak, Diederick E. Grobbee, Arno W. Hoes. b-Blockers May Reduce Mortality and Risk of Exacerbations in Patients With Chronic Obstructive Pulmonary Disease. Arch Intern Med. 2010;170:880-887

Beta-blockers in COPD patients: Reduced mortality

Frans H. Rutten, Nicolaas P. A. Zuithoff, Eelko Hak, Diederick E. Grobbee, Arno W. Hoes. b-Blockers May Reduce Mortality and Risk of Exacerbations in Patients With Chronic Obstructive Pulmonary Disease. Arch Intern Med. 2010;170:880-887

Beta-blockers in COPD patients: Reducted mortality

Pulmonary specialists in COPD patients: Reduced survival

BETA-BLOCKERS AND LIPIDS

** **** **

**

**

** ****

*

+10

0

–10

–20

–30

–40

6 12 18 24 30 36 months

Mepindolol 10 mg/day (n = 16)

Bisoprolol 10 mg/day (n = 17)

Propranolol 160 mg/day (n = 15)

Atenolol 100 mg/day (n = 22)

vs. baseline*p<0.05**p<0.01

Δ%

HD

L-c

hole

ste

rol

HDL-cholesterol during treatment with different beta-blockers

Fogari R et al. J Cardiovasc Pharmacol 1990; 16 (Suppl 5): S 76–80

74

HDL-cholesterolTotal cholesterol

5 years4 years3 years2 years1 yearstart

mm

ol/

L

0

1

2

3

4

5

6

7

8

LDL-cholesterolTriglycerides

Frithz G. Cardiovasc Drugs Ther 1993;7(suppl 2):424

Bisoprolol: β1-selectivity and Lipid Metabolism in Long-term Therapy

BETA-BLOCKERS AND DIABETES

William J Elliott, Peter M Meyer. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369: 201–07

Risk of de novo diabetes mellitus during anti-hypertensive therapy

Treatment with valsartan and risk of de novo diabetesmellitus(NAVIGATOR trial)

NEJM 2010

NEJM 2010

Treatment with valsartan and cardiovascular complications(NAVIGATOR trial)

Concomitant therapy and the risk of de novo diabetesNAVIGATOR Trial

Shen L, Shah BR, Reyes EM et al. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ 2013;347:f6745

Diuretics

1.50

1.40

1.30

1.20

1.10

1.00

0.90

0.80

0.70b-blockers Statins Calcium

antagonists

Haz

ard

rat

io (

95

% C

I)

1.10

1.231.32

0.95

170

160

150

140

130

120

110

100

10

9

8

7

6

A B CA

A: initial value

B: after 2 weeksof bisoprolol

C: after 2 weeksof placebo

B C

(PCB >0.05)

Glucose

(mg

/dL)

HbA1c

(%)

n=20

(PCB >0.05)

ß1-selectivity and glucose metabolism in patients with DM type 2 and concomitant hypertension

Janka HU et al. J Cardiovasc Pharmacol 1986;8(Suppl. 11):96–99

BETA-BLOCKERS AND PAD

Use of beta-blockers was associated with a 53% significant reduction in the incidence of new coronary events

Freedom from MALE was significantly higher in the bisoprolol-treated group than in the carvedilol group

84

Soga Y et al. J Atheroscler Thromb 2014;21:691-702

MALE = major adverse limb events incl. any repeated revasularization [any endovascular procedure, any surgical revision or the use of thrombectomy or thrombolysis] and major amputation

BETA-BLOCKERS AND ERECTILE DYSFUNCTION

0

0,5

1

1,5

2

2,5

3

3,5

4

Amlodipine

(n=103)

Bisoprolol

(n=389)

Bisoprolol/HCTZ

(n=333)

Enalapril (n=102) HCTZ (n=134) Placebo (n=150)

%

Self-reported erectile dysfunction during 6-14 weeksof antihypertensive therapy

Prisant LM et al.: Self-reported sexual dysfucntion in men and women treated with bisoprolol, hydrochlorothiazide, enalapril, amlodipine, placebo, or bisoprolol/hydrochlorothiazide. J Clin Hypertens 1999; 1: 22

0

5

10

15

20

25

30

35

% patients

3,1%

Complaints on erectile dysfunction and knowledge on the type of drug and side effects

„Blinded”

Silvestri A. et al. Eur Heart Journal 2003, 24: 1928-32

0

5

10

15

20

25

30

35

3,1%

15,6%

% patients

„Blinded” Known drug



0

5

10

15

20

25

30

35

3,1%

15,6%

31,2%

% patients

„Blinded” Known drug Known drug and SE



Patients who reported erectile dysfunction respondedsimilarly to sildenafil and placebo


Ko DT i wsp., JAMA 2002; 288: 351-7

Beta-blocker therapy was not associated with a significant absolute annual increase in

risk of reported depressive symptoms (6 per 1000 patients;95% CI [-7 to 19])

Beta-blockers were associated with a small significant annual increase in risk of reported

fatigue (18 per 1000 patients; 95% CI, [5-30])

Beta-blockers were also associated with a small, significant annual increase in risk of

reported sexual dysfunction (5 per 1000 patients; 95% CI, [2-8])

None of the risks of adverse effects differed significantly by degree of -blocker lipid

solubility

The risk associated with reported fatigue was significantly higher for early-generation

than for late-generation beta-blockers (P=.04).

ADVANCES IN MEDICINE 2013 June 29-30, 2013 Hong Kong

Ko DT i wsp., JAMA 2002; 288: 351-7

Beta-blocker therapy was not associated with a significant absolute annual increase in

risk of reported depressive symptoms (6 per 1000 patients;95% CI [-7 to 19])

Beta-blockers were associated with a small significant annual increase in risk of reported

fatigue (18 per 1000 patients; 95% CI, [5-30])

Beta-blockers were also associated with a small, significant annual increase in risk of

reported sexual dysfunction (5 per 1000 patients; 95% CI, [2-8])

None of the risks of adverse effects differed significantly by degree of -blocker lipid

solubility

The risk associated with reported fatigue was significantly higher for early-generation

than for late-generation beta-blockers (P=.04).

The conventional wisdom that beta-blocker therapy is associated with substantial risks of depressive symptoms, fatigue, and sexualdysfunction is not supported by data from clinical trials.

The risk was not associated with lipid-solubility but low b1-selectivity

Erectile dysfunction and treatment with different beta-blockers (MR NOED study)

Brixius K et al.. Clin Exp Pharmacol Physiol 2007; 34: 327-31

metoprolol

nebiwolol

BETA-BLOCKERS AND STROKE

Systolic blood pressure and risk of stroke (Prospective Cohort Study Collaboration)

120 160

256

64

16

4

1

Systolic BP (mmHg)

Age (years)

80-89

70-79

60-69

50-59

40-49

Lancet 2002; 360: 1903

Stro

ke d

eath

s

200

Hypertensive therapy: effects calculated on BP reduction

SBP difference (mmHg)

CA/placebo

ACE/plac

Better/worse

ARB/other

ACE/CA

CA/DBB

ACE/DBB

Lancet 2003; 362: 1527-35.

0.25

0.50

0.75

1.00

1.25

1.50

-10 -8 -6 -4 -2 0 2 4

• Atenolol (once daily) was used in 80% of clinical trials

• Atenolol (once daily) is a weak antihypertensive drug

• Risk of stroke is mostly related to blood pressure level

Beta-blockers and stroke prevention

Evidence-based on clinical trials

Beta-blockers reduce risk of stroke

Hypertensive treatment lowers cardiovascular risk in young and middle-aged population

Musini VM et al. Pharmacotherapy for hypertension in adults aged 18 to 59 years (Review). 2017, Issue 8. Art. No.: CD008276.

BETA-BLOCKERS AND ACC/AHA AND

NICE GUIDELINES

Isam Al-Karkhi et al. Comparisons of automated blood pressures in a primary health care setting with self-measurements at the office and at home using the Omron i-C10 device. Blood Press Monit 2015: 20: 98-103

Difference between automated BP readings and mesurement by medical personel(SMOB, self-measurement by the patient at the office)

141,0±18/85,4±9,9 - 140,3±18/86,3±9,5

Dahlöf B et al.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

ASCOT BPLA trial: unmet primary clinical endpoint

Dahlöf B et al.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

ASCOT BPLA trial: unmet primary clinical endpoint

Why atenolol?

Why once daily?

Why 50 mg?

Bisoprolol

Atenolol ± SEM

(mm

Hg

)

SBP DBP HR

0

– 5

–10

–15

–20

–13.4

p<0.01

–3.7

–12.7

–13.8

–16.3

–5.7

p=0.001

p=0.13

Dm

ea

n B

P f

rom

24-h

r m

onitori

ng 0

– 5

–10

–15

–20

Bisoprolol and atenolol in hypertensive subjects > 60

Neutel JM et al. Am J Cardiol 1993; 72: 41–46

Db

ea

ts/m

in

Bryan Williams, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015 September 21, 2015

Bisoprolol – most effective in reduction of diastolic blood pressure (PATHWAY-2)

Bryan Williams, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015 September 21, 2015

Bisoprolol was most effective in patients with high-renin resistant hypertension (PATHWAY-2)

RR Holman et al.. Long-Term Follow-up after Tight Control of Blood Pressure in Type 2 Diabetes.N Eng J Med. 2008;359:1565-76

UKPDS at 20-year follow up: significant reduction in mortality in patients treated with beta-blocker

• No data on basal heart rate

• Heart rate as an indicator of higher doses = more severe hypertension

• Heart rate < 50/min is not normal (!)

• Mostly (78% patients) studies with atenolol

• Relationship not observed in placebo studies

• Outcomes in the trials mostly affected by BP difference

• Beta-blocker are not given in hypertensive pts according to HR

Beta-blocker-induced heart rate lowering and cardiovascular outcomes

Objections

S Bangalore, et al. Beta-Blocker Use and Clinical Outcomes in Stable Outpatients With and Without Coronary Artery Disease. JAMA. 2012;308(13):1340-1349

In patients with prior MI use of beta-blockers was not associatedwith a lower risk of composite cardiovascular eventsPropensity score analysis of data from REACH Registry

• Mostly (78% patients) studies with atenolol

• Observational study

• 36% patients on beta-blockers

• 74% without beta-blockers

• Unobserved confounding by atrial fibrillation, renal dysfunction, COPD

• Comparing current users with nonusers and past users

In patients with prior MI use of beta-blockers was not associatedwith a lower risk of composite cardiovascular eventsPropensity score analysis of data from REACH Registry

Chocolate Consumption, Cognitive Function, and Nobel Laureates

Franz Messerli. N Eng J Med. 2012; 167: 1562-4

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Right Beta Blockers for the Right Patientsperkicabangmalang.org/assets/files/4. Right Beta... · Right Beta Blockers for the Right Patients JOHN DOE, MD SUBTITLE 32 PT ARIAL BOLD