2.

Beta-blockers in the
treatment of
hypertension
associated with
sympathetic overdrive

IDN/CONCO/0319/0012
 Beta-blockers can intervene at many points in the cardiovascular continuum1

Myocardial
Coronary infarction Arrhythmias Sudden
thrombosis and loss of muscle death

Neurohormonal
Myocardial activation
ischemia

Beta- Remodelling
CHD
blockers

Atherosclerosis Ventricular
LVH enlargement

Risk factors
• Hyperlipidemia CHF Left ventricular hypertrophy (LVH)
• Hypertension Death Coronary heart disease (CHD)

• Diabetes Chronic heart failure (CHF)

• Smoking
Graph adapted from reference 1

2 1. Adapted from Willenheimer R, Erdmann E. Beta-blockade across the cardiovascular continuum – when and where to use? Eur Heart J Suppls. 2009;11(Suppl A):A1–2.

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 Why beta1-selectivity is important in the treatment of hypertension
associated with sympathetic overdrive1,2
Primary distribution of beta-receptors and effects of stimulation1

Beta1 receptors Beta2 receptors

 Contractility and heart rate1

Myocardium
 Myocardial necrosis/apoptosis1

Bronchial smooth muscle  Bronchodilation1

Blood vessel smooth

 Vasodilation1
muscle

Kidney  Renin release1

Highly selective beta1-blockers inhibit sympathetic activity in the heart and kidney, preserve beta2-
mediated vasodilation, and reduce the risk of adverse effects mediated by blockade of beta2 receptors
in the lungs and peripheral tissues2

1. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton, CT: People's Medical Publishing House-USA;2011
3
2. Egan BM, Basile J, Chilton RJ et al. Cardioprotection: the role of beta-blocker therapy. J Clin Hypertens. 2005;7(7):409–16.
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 Beta1-blockade may be particularly beneficial in hypertensive patients with
central obesity/diabetes/insulin resistance1

DM2/Obese
Type 2 diabetes mellitus (DM2)

 Insulin resistance
Beta1-blockade

 Insulin/Leptin

 Norepinephrine release

Benefits are
mediated by blockade
of beta1-receptors  PRA  Angiotensin II
Plasma renin activity (PRA)

Beta1-stimulation-induced  BP +  Intra-glomerular
Ventricular
cardiac and coronary damage non-dipping pressure
arrhythmias
( atheroma) at night + nephropathy
Blood pressure (BP)
Graph adapted from reference 1

4
1. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton, CT: People's Medical Publishing House-USA;2011; Fig. 3-8
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 Beta-blockers can reduce mortality in the overweight/obese, high-risk
hypertensive patient with type 2 diabetes1-5
20-year follow up of the United Kingdom Prospective Diabetes Study (UKPDS)4,5

0.8
ACE inhibitor Angiotensin-converting enzyme (ACE)
Proportion with event

Beta-blocker

0.6 *
23% reduction in
death from any
cause in patients
0.4 receiving a
beta-blocker
(*p<0.05) 1
0.2

0
4 8 12 16 20
Graph adapted from reference 1 Years since randomization
1. Cruickshank JM. The Modern Role of Beta-blockers in Cardiovascular Medicine. Shelton, CT: People's Medical Publishing House-USA;2011; Fig. 3-15
2. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes; UKPDS 38.
BMJ. 1998;317:703–13.
3. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type-2 diabetes: UKPDS 39.
BMJ. 1998:313–20.
4. Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow-up after tight control of blood pressure in type-2 diabetes. N Engl J Med. 2008;359:1565–76.
5
5. Coats AJS, Cruickshank JM. Hypertensive subjects with type-2 diabetes, the sympathetic nervous system, and treatment implications. Int J Cardiol. 2014;174:702–9.
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 Beta-blockers offer additional protection to BP reductions in preventing
recurrent events in patients with a history of CHD1

No of No of Relative risk Relative risk

trials events (95% CI) (95% CI)
Trials of beta-blockers
People with history of CHD 37 2524 0.71 (0.66 to 0.78)
Entry after acute myocardial infarction 27 2155 0.69 (0.62 to 0.76)
Entry after long term coronary heart disease 11 369 0.87 (0.71 to 1.06)

People with no history of CHD 6 851 0.89 (0.78 to 1.02)

p<0.001
Trials of drugs other than beta-blockers
People with history of CHD 37 5834 0.85 (0.79 to 0.91)
People with no history of CHD 24 3217 0.84 (0.79 to 0.90)

All trials except ones of beta-blockers in people 64 9417 0.85 (0.81 to 0.89)
with history of CHD
0.5 0.7 1 1.4 2
Blood pressure(BP) Coronary heart disease(CHD) Treatment better Placebo better

Graph adapted from reference 1

6 1. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in
the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665. doi:10.1136/bmj.b1665.
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7
2018 ESC guideline
Recommended Pharmacological therapy for hypertension:
5 Major Classes
ACEi, ARB

form the basis of

antihypertensive diuretics
therapy
E
CCB

Beta Blockers

European Heart Journal (2018) 00, 1–98

7 IDN/CONCO/0319/0012
2018 ESC guideline _ Risk Factors (1)

Heart rate should

also be recorded at
the time of BP
measurements
because resting
heart rate is an
independent
predictor of
CV morbid or fatal
events

8 IDN/CONCO/0319/0012
 NICE guidelines also recommend beta-blockers as initial therapy for
hypertension in younger people1

Consider beta-blockers in younger people

with evidence of increased sympathetic drive
The NICE evidence review identified four studies that reported beta-blockers and
ACE inhibitors as being more effective at lowering blood pressure in younger
people than calcium channel blockers or thiazide-type-diuretics.

The guidelines do not generally recommend beta-blockers as a preferred initial

treatment option for hypertensive patients, but beta-blockers may be considered
for initial therapy of hypertension in younger people, particularly:

• those with an intolerance or contraindication to ACE inhibitors and

angiotensin II receptor antagonists or
• women of child-bearing potential or
• people with evidence of increased sympathetic drive.

Please refer to abbreviated product information in chapter 7 which may vary by country.
1. NICE Guideline CG127. Hypertension: The clinical management of primary hypertension in adults. August 2011.
Available at: https://www.nice.org.uk/guidance/cg127/evidence/full-guideline-248588317. Last accessed March 2016.

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 Canadian guidelines recommend beta-blockers as an initial antihypertensive
therapy1

Recommendations for individuals with diastolic and/or systolic hypertension

Initial therapy should be monotherapy with:
• a thiazide/thiazide-like diuretic (Grade A)
• a beta-blocker (in patients <60 years of age, Grade B)
• an ACE inhibitor (in non-black patients, Grade B)
• a long-acting calcium channel blocker (CCB) (Grade B) or
• an angiotensin receptor blocker (ARB) (Grade B).

Please refer to abbreviated product information in chapter 7 which may vary by country.

10 1. Daskalopoulou SS, Rabi DM, Zarnke KB et al. The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis,
assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2015;31(5):549–68.
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 2017ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA
Guideline for the Prevention, Detection, Evaluation, and Management
of High Blood Pressure in Adults

• The overall goal of treatment should be reduction in BP, in the context of underlying CVD risk. Five drug
classes have been shown, in high-quality RCTs, to prevent CVD as compared with placebo (diuretics,
ACE inhibitors, ARBs, CCBs, and beta blockers)
• Beta blockers are not recommended as first-line agents unless the patient has IHD or HF. These are
preferred in patients with bronchospastic airway disease requiring a beta blocker. n Bisoprolol and
metoprolol succinate are preferred in patients with HFrEF.
• Adults with HFpEF and persistent hypertension after management of volume overload should be
• prescribed ACE inhibitors or ARBs and beta blockers titrated to attain SBP of less than 130 mm Hg
• In patients with chronic aortic dissection, observational studies suggest lower risk for operative repair
with beta-blocker therapy (S9.10-1). In a series of patients with type A and type B aortic dissections,
beta blockers were associated with improved survival in both groups, whereas ACE inhibitors did not
improve survival

2017 High Blood Pressure Clinical Practice Guideline. JACC, MA Y 1 5 , 2 0 1 8 : e 1 2 7 – 2 4 8

11

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 THANKS

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