Download Use of Beta-Blockers In patients With Diabetes Mellitus

‫بسم هللاا الرحمن الرحيم‬
‫‪1‬‬
Use of Beta-Blockers
In patients With Diabetes Mellitus
Professor Taalat Abd El-Aatty
Diabetes & Metabolism
Alexandria University
Questions?
1. Are β-blockers contraindicated in diabetes
mellitus?
2. Are β-blockers still considered as first line
treatment of hypertension?
3. Are β-blockers the first line treatment for
control of hypertension in patients with
diabetes?
BETA-BLOCKER
• Beta 2 – on bronchial and vascular smooth
muscle - relaxation
• Increased in heart failure
• Beta 3 – mediate vasodilatation by release of
nitric oxide
Antihypertensive effect –
1.Inhibition of prejunctional beta receptors on
the terminal neurons
2.Reduction of central adrenergic outflow
3.Decreased Renin-angiotensin system –beta
receptors mediate renin release
• Thus decreases after load and wall stress
Beta-Blockers: Side Effects
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Dizziness, fatigue.
Intermittent claudication,
Airway obstruction in asthma.
Heart block.
Raynaud’s phenomenon.
Erectile dysfunction (ED)
Hypoglycaemia.
Increase in insulin resistance or new-onset
diabetes.
BB with VD
Properties
Beta-Blockers: Contraindications
• Asthma.
• Atrioventricular block.
Diabetes PER SE is Not a
Contraindication for use of β.blocker
Beta-Blockers
• Increased insulin resistance and a higher
incidence of new-onset diabetes mellitus were
reported in early trials with beta-blockers.
• However, more modern agents such as
bisoprolol and carvedilol appear to have no
detrimental effect on glucose metabolism.
Beta-Blockers
• Existing diabetes mellitus is not a contraindication to beta-blockade, although b1selective agents are preferable in insulindependent patients, to avoid masking
hypoglycaemia.
Beta-Blockers
• Patients with diabetes and concomitant CHF or
CAD are among those who can benefit most from
beta-blockers.
• European guidelines recommend β-blockers for
all diabetic patients with acute cardiac syndrome,
post-MI, and in CHF.
• Post-MI beta-blockade reduces mortality by 23%
in diabetic patients.
• In CHF studies, β-blockers have consistently
shown a significant benefit in patients with
diabetes.
Meta-analysis by Haas et al. showed that compared
with placebo, β-blockers for CHF significantly reduces
all-cause mortality by 16% in patients with DM.
COPERNICUS Study
 In the Carvedilol Prospective Randomized
Cumulative Survival (COPERNICUS) study of
carvedilol, in patients with advanced HF, allcause mortality was reduced equivalently in
diabetic and nondiabetic patients.
Now back to the 1st question
1. Are β-blockers contraindicated in diabetes
mellitus?
* β-blockers are not contraindicated in patients
with diabetes mellitus.
* β-blockers are highly indicated in diabetics
with CAD or CHF.
Questions?
1. Are β-blockers contraindicated in diabetes
mellitus?
2. Are β-blockers still considered as first line
treatment of hypertension?
3. Are β-blockers the first life treatment for
control of hypertension in patients with
diabetes?
JNC 7: β-blockers 1st line anti-hypertensive
Recommended Drugs
Compelling
Indication*
Heart failure
Post-MI
Diabetes
Chronic kidney
disease
DIURETI
C
•
•
BB
ACEI
ARB
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•
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CCB
Aldo
ANT
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NICE/BHS 2006: removed β-blockers
BMJ 2008; (including LIFE and ASCOT)
A meta-analysis favour the use of β-blockers
 β-blockers
Largest Meta-analysis
Conclusions: With the exception of the extra
protective effect of β blockers given shortly after a
myocardial infarction and the minor additional effect
of calcium channel blockers in preventing stroke, all
the classes of blood pressure lowering drugs have
a similar effect in reducing CHD events and
stroke for a given reduction in blood pressure so
excluding material pleiotropic effects.
BMJ. 2009 May 19
Recent Guidelines 2009
Large-scale meta-analyses of available data confirm that
major antihypertensive drug classes, (diuretics, ACE
inhibitors, calcium antagonists, angiotensin receptor
antagonists, and b-blockers) do not differ significantly
for their overall ability to reduce BP in hypertension.
 There is also no evidence that major drug classes
differ in their ability to protect against overall
cardiovascular risk or cause-specific cardiovascular
events, such as stroke and myocardial infarction.
 Diuretics, ACE inhibitors, calcium antagonists,
angiotensin receptor antagonists and b-blockers
can all be considered suitable for initiation of
antihypertensive treatment, as well as for its
maintenance.
 Keeping the number of drug options large increases
the chance of BP control in a larger fraction of
hypertensives.
 Cardiovascular protection by antihypertensive
treatment substantially depends on BP
lowering per se, regardless of how it is obtained.
 The traditional ranking of drugs into first, second, third
and subsequent choice, has now little scientific
justification and should be avoided.
In the absence of compiling indications
 Use any anti-hypertensive
from the 5 major classes.
To answer our 2nd question
1. Are β-blockers contraindicated in diabetes
mellitus?
2. Are β-blockers still considered as first line
treatment of hypertension?
* The answer is yes according to large recent
meta-analysis and the revised European
guidelines in 2009.
Questions?
1. Are β-blockers contraindicated in diabetes
mellitus?
2. Are β-blockers still considered as first line
treatment of hypertension?
3. Are β-blockers the first life treatment for
control of hypertension in patients with
diabetes?
United Kingdom Prospective
Diabetes Study (UKPDS)
• Design: Randomized, controlled trial comparing an
ACE inhibitor with a b-blocker in preventing
complications of type 2 diabetes.
• Population: 1148 patients with hypertension
and type 2 diabetes.
• Treatment: 758 patients allocated to tight
control of BP:
Captopril (n=400)
Atenolol (n=358)
UKPDS
50
Patients With Events (%)
Less tight blood pressure control
Captopril
40
Atenolol
P=0.43
30
20
10
0
0
1
2
3
4
5
6
Years from Randomization
7
8
9
No. of patients at risk:
Captopril
Atenolol
400
358
UKPDS Group. BMJ. 1998;317:713-720
327
314
257
237
124
112
UKPDS
• Conclusion:
 Captopril and atenolol produced similar
reductions in BP in hypertensive diabetics.
 Both drugs were equally effective in reducing
risk of:
o Fatal and non-fatal diabetic complications
o Death related to diabetes
o Heart failure
o Progression of retinopathy
JNC 7: β-blockers can be used in diabetics
Recommended Drugs
Compelling
Indication*
DIURETI
C
BB
ACEI
ARB
Heart failure
Post-MI
•
•
•
•
•
•
Diabetes
•
•
•
•
•
•
Chronic kidney
disease
CCB
Aldo
ANT
•
•
•
ADA
2011 ADA Recommendation
Level of evidence C
(C)
• Pharmacologic therapy for patients with diabetes and
hypertension should include either an ACE inhibitor or
ARB.
• If needed to achieve blood pressure targets, a thiazide
diuretic should be added to those with an
estimatedGRF ≥30 mL/min and a loop diuretic for
those with an estimated GFR <30.
Level of evidence C:
Supportive evidence from poorly controlled or
uncontrolled studies.
Evidence from RCTS with ≥ 1 major or ≥ 3 minor
methodological flaws that could invalidate results.
Evidence from observational studies with high potential
for bias.
Evidence from case series or case reports.
Conflicting evidence with the weight of evidence
supporting the recommendation.
If Blood Pressure >130/80 mm Hg
in Diabetes + Albuminuria
START with ACEI or ARB ± diuretic)
If BP Still Not at Goal (130/80 mm Hg)
Add CCB or b
blocker
If BP Still Not at Goal (130/80 mm Hg)
Consider low dose aldosterone antagonists#
If BP Still Not at Goal (130/80 mm Hg)
Add Vasodilator (hydralazine, minoxidil)
European Guidelines
Meta-analyses of available trials show that in
diabetes all major antihypertensive drug classes
protect
against
cardiovascular
complications,
probably because of the protective effect of BP
lowering per se.
They can thus all be considered for treatment.
Questions?
1. Are β-blockers contraindicated in diabetes
mellitus?
2. Are β-blockers still considered as first line
treatment of hypertension?
3. Are β-blockers the first life treatment for
control of hypertension in patients with
diabetes?
* Definitely not to start with in diabetics with
micro-abluminuria in which ACE.I or ARBs are
proved to have more benfit.
Conclusion
1. Are β-blockers contraindicated in diabetes
mellitus? NO
2. Are β-blockers still considered as first line
treatment of hypertension? YES
3. Are β-blockers the first life treatment for
control of hypertension in patients with
diabetes? NO
THANK YOU