الرحمن االله بسم الرحيم

1

Use of Beta-Blockers In patients With Diabetes Mellitus

Professor Taalat Abd El-AattyDiabetes & 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

• 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 contra-indication to beta-blockade, although b1-selective agents are preferable in insulin-dependent 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, all-

cause 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

Compelling Indication*

Recommended Drugs

DIURETIC BB ACEI ARB CCB

Aldo ANT

Heart failure • • • • •

Post-MI • • •

Diabetes • • • • •

Chronic kidney disease

• •

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 ProspectiveDiabetes Study (UKPDS)

• Design: Randomized, controlled trial comparing anACE inhibitor with a b-blocker in preventingcomplications of type 2 diabetes.

• Population: 1148 patients with hypertensionand type 2 diabetes.

• Treatment: 758 patients allocated to tight control of BP:Captopril (n=400)Atenolol (n=358)

UKPDS

Years from Randomization

124112

257237

327314

400358

CaptoprilAtenolol

No. of patients at risk:

Patie

nts

With

Eve

nts

(%)

0 21 3 54 6 87 9

Less tight blood pressure control

Captopril

AtenololP=0.43

0

10

20

30

40

50

UKPDS Group. BMJ. 1998;317:713-720

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 complicationso Death related to diabeteso Heart failure o Progression of retinopathy

JNC 7: β-blockers can be used in diabetics

Compelling Indication*

Recommended Drugs

DIURETIC BB ACEI ARB CCB

Aldo ANT

Heart failure • • • • •

Post-MI • • •

Diabetes • • • • •

Chronic kidney disease

• •

ADA

2011 ADA RecommendationLevel of evidence 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.

(C)

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.

START with ACEI or ARB ± diuretic)

If BP Still Not at Goal (130/80 mm Hg)

If BP Still Not at Goal (130/80 mm Hg)

Add Vasodilator (hydralazine, minoxidil)

If BP Still Not at Goal (130/80 mm Hg)

If Blood Pressure >130/80 mm Hg in Diabetes + Albuminuria

Add CCB or b blocker

Consider low dose aldosterone antagonists#

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