do third generation beta blockers work better in...

11

Do Do thirdthird generationgeneration

beta beta blockersblockers workwork

betterbetter in in cardiovascularcardiovascular

treatmenttreatment??Ceyhun CEYHAN Prof. MD, FESCCeyhun CEYHAN Prof. MD, FESC

Adnan Menderes Adnan Menderes UniversityUniversity

FacultFacult

of of MedicineMedicine

DepartmentDepartment

of of CardiologyCardiology, Ayd, Aydıın,n,TurkeyTurkey

22

ObjectObjectiivesves

Identify the shortcomings of Identify the shortcomings of traditional (nontraditional (non--vasodilatingvasodilating

Beta Beta

Blockers)Blockers)

Identify the advantages of the Identify the advantages of the VasodilatingVasodilating

Beta BlockersBeta Blockers

33

The

Evaluation

of Beta-blockers

198019801980 201020102010196019601960 199019901990 200020002000197019701970

NadololNadolol19791979

TimololTimolol19811981

Labetalol1984

LabetalolLabetalol19841984

PropranololPropranolol19671967

Acebutolol1984

AcebutololAcebutolol19841984

MetoprololMetoprololTartrateTartrate

19781978

SotalolSotalol19921992

BisoprololBisoprolol19921992

Carvedilol

1995

CarvedilolCarvedilol

19951995 Carvedilol

CR2006


CRCR20062006

Betaxolol1989

Penbutolol1987

PenbutololPenbutolol19871987

Nebivolol2007

NebivololNebivolol20072007

PropranololPropranolol

XL XL 20032003

VasodilatingVasodilating

--blockers are yellowblockers are yellow

Date of New Drug Application ApprovalDate of New Drug Application ApprovalDate of New Drug Application Approval

LM Prisant

2008

Pindolol1982

PindololPindolol19821982

Propranolol

LA1983

PropranololPropranolol

LALA19831983

Esmolol1986

EsmololEsmolol19861986

Carteolol1988

CarteololCarteolol19881988

MetoprololSuccinate

1992

MetoprololMetoprololSuccinateSuccinate

19921992

Atenolol1981

AtenololAtenolol19811981

44

Beta blocker HistoryFirst Generation

NonselectivePropranolol

Timolol

Second GenerationSelectiveAtenolol

MetoprololBisoprolol

Third Generation

VasodilatoryLabetalolCarvedilolNebivolol

First GenerationNonselectivePropranolol

Timolol

Second GenerationSelectiveAtenolol

MetoprololBisoprolol

Third Generation

VasodilatoryLabetalolCarvedilolNebivolol

55HR, heart rate; BP, blood pressure.HR, heart rate; BP, blood pressure.1. 1. TseTse

WY et al. WY et al. DiabetDiabet MedMed. 1994;11(2):137. 1994;11(2):137--144. 144. 2. 2. FonarowFonarow

GC. GC. Am J MedAm J Med. 2004;116(Suppl 5A):76S. 2004;116(Suppl 5A):76S--88S. 88S. 3. Bell DS. 3. Bell DS. The EndocrinologistThe Endocrinologist. 2003;13:116. 2003;13:116--123.123.

Cardiac Benefits of Beta-BlockadeAntiatherogenic—reduces inflammation, shear

stress, endothelial dysfunction and risk for plaque rupture1,2,3

Antiarrhythmic1

•

decreases HR2

•

decreases sympathetic activity1

•

increases cardiac vagal

tone1

Anti-ischemic1

•

decreases HR and BP2

•

prolongs diastole (filling coronary arteries)2

Reverses cardiac remodeling2

66

Compelling

Indications

for

Beta- Blockers

77

BetaBeta ReceptorsReceptors

ßß11

HeartHeart

KidneysKidneys

Fat cellsFat cells

ßß2 2

LungsLungs

Skeletal MusclesSkeletal Muscles

Liver/PancreasLiver/Pancreas

88

Heterogenous

Drug Class

ßß11

//ßß22SelectivitySelectivity

ßß--blockersblockers

MetabolicMetabolicProfileProfile

SideSideEffectsEffects

VasodilatoryVasodilatoryPropertiesProperties

OutcomesOutcomesTrialsTrials

--blockersblockers

Which One?Which One?

99

NonNon--VasodilatingVasodilating

Beta Beta BlockerBlocker EffectsEffects

on on PeripheralPeripheral

VasculatureVasculature

1010

Side Effects ofSide Effects of

TraditionalTraditional

Beta Beta BlockersBlockers

FatigueFatigue

Sexual Sexual ddysfunctionysfunction

DepressionDepression

Cold extremitiesCold extremities

DecreaseDecreasedd

eexercisexercise

ttoleranceolerance

Metabolic side effectsMetabolic side effects

1111

VasodilatingVasodilating Beta blockersBeta blockers

Better side effect profileBetter side effect profile

Better TolerabilityBetter Tolerability

Better efficacyBetter efficacy

1313

1

-Selectivity

40,7

15,6

4,230,73 0,49

05

101520253035404550

Nebivolol Bisoprolol Carvedilol Metoprolol Bucindolol

Ki

2/Ki

1

Brixius

K, et al. Br J Pharmacol 2002;133:1330-1338.

1414

Peripheral Vasodilating

ActivitySeveral MechanismsSeveral Mechanisms

Bucindolol

(not marketed because of BEST)• Produces vasodilatation by ? cGMP-dependent mechanism

Carvedilol, labetalol:

due to 1

-blockade

Celiprolol:

due to 2

-adrenergic receptor agonism (not marketed in US, due to hepatic dysfunction)

Nebivolol• Lipophilic• Racemic

mixture

• Nitric oxide (NO)-mediated vasodilator properties

BucindololBucindolol

(not marketed because of BEST)(not marketed because of BEST)•• Produces vasodilatation by ? Produces vasodilatation by ? cGMPcGMP--dependent dependent mechanism mechanism

CarvedilolCarvedilol, , labetalollabetalol::

due to due to 11

--blockadeblockade

CeliprololCeliprolol::

due to due to 22

--adrenergic receptor adrenergic receptor agonismagonism (not marketed in US, due to hepatic dysfunction)(not marketed in US, due to hepatic dysfunction)

NebivololNebivolol•• LipophilicLipophilic•• RacemicRacemic

mixturemixture

•• Nitric oxide (NO)Nitric oxide (NO)--mediated vasodilator mediated vasodilator propertiesproperties

1515

Nebivolol:Vascular Relaxation via the L-arginine–Nitric-Oxide Pathway

VeverkaVeverka

A, et al. A, et al. Am Am PharmacotherPharmacother 2006;40:13532006;40:1353--1360.1360.

LL--argininearginine

Nitric Nitric oxideoxide(diffuses into smooth muscle)(diffuses into smooth muscle)

EndothelialEndothelialNOSNOS

GuanylylGuanylyl

CyclaseCyclase

Activated Activated GuanylylGuanylyl

CyclaseCyclase

cGMPcGMPGTPGTP

Vascular Smooth Muscle RelaxationVascular Smooth Muscle Relaxation

––

1616

Hemodynamic Effects of Nebivolol and Atenolol

Left ventricularend-diastolic volume (mL)

Left ventricular endsystolic volume (mL)

Stroke volume (mL)

Heart rate (beats/min)

Cardiac output (L/min)

Peripheral resistance (dyne/cm-5)

-40 -30 -20 -10 0 10 20 30Percent change vs baseline

-13.25.8

7.1

-10.8-28.2

20.6

-1.49.2

10.65.7

Ejection fraction (%)7.8

-2.1

3.6

-24.0

Atenolol (100 mg/qd)Nebivolol(5 mg/qd)

Kamp, et al. Am J Cardiol 2003;92:344

*At 2 weeks*At 2 weeks

1717

NebivololNebivolol

Reduces PeripheralReduces Peripheral

Vascular Vascular ResistanceResistance

Perc

ent

chan

ge

Perc

ent

chan

ge v

svsba

selin

eba

selin

e

Peripheral resistancePeripheral resistance(dyne/cm5)(dyne/cm5)

Stroke volumeStroke volume((mLmL))

Cardiac outputCardiac output(L/min)(L/min)

**

**

*N=25; parameters at 2 weeks*N=25; parameters at 2 weeksAt 2 weeks; *P<0.05 At 2 weeks; *P<0.05 vsvs

pretreatment. Change in SBP/DBP was pretreatment. Change in SBP/DBP was --19/12 mm Hg for 19/12 mm Hg for nebivololnebivololAdapted from Adapted from KampKamp

O et al. Am J O et al. Am J CardiolCardiol. 2003;92:344. 2003;92:344--348348

-15-10

-50

510

1520

25

Heart rateHeart rate((bpmbpm))

Beat

s pe

r minut

eBe

ats

per

minut

e

1919

Myocardial Infarction: Is there a Class Effect?

Freemantle

N, et al. BMJ 1999;318:1730-7.FreemantleFreemantle

N, et al. N, et al. BMJ BMJ 1999;318:17301999;318:1730--7.7.

Total Mortality Reduction after Myocardial InfarctionTotal Mortality Reduction after Myocardial InfarctionTotal Mortality Reduction after Myocardial InfarctionAcebutololAcebutololAcebutolol

AlprenololAlprenololAlprenolol

AtenololAtenololAtenolol

Carvedilol

*CarvedilolCarvedilol

**

MetoprololMetoprololMetoprolol

OxprenololOxprenololOxprenolol

PindololPindololPindolol

PractololPractololPractolol

PropranololPropranololPropranolol

SotalolSotalolSotalol

TimololTimololTimolol

XamoterolXamoterolXamoterol|0||00

|1||11

|2||22

|3||33

|4||44

|5||55

|6||66

Odd Ratio of DeathOdd Ratio of DeathOdd Ratio of Death

n = 54,234n = 54,234n = 54,234

*

Meta-analysis did NOT include CAPRICORN Trial (Lancet 2001;357:1385-90), which showed 23%

in all-cause mortality (Hazard ratio = 0.77 [95% Confidence interval = 0.60-0.98], p=0.03)

**

MetaMeta--analysis did NOT include CAPRICORN Trial analysis did NOT include CAPRICORN Trial (Lancet 2001;357:1385(Lancet 2001;357:1385--90), which showed 23%90), which showed 23%

in allin all--cause mortality (Hazard ratio = 0.77 [95% cause mortality (Hazard ratio = 0.77 [95% Confidence interval = 0.60Confidence interval = 0.60--0.98], p=0.03) 0.98], p=0.03)

••••••

•••

•••

•••

•••

•••

•••

•••

•••••••••

2020

CAPRICORN Study Design

Dargie

HJ, et al. Eur J Heart Fail 2000;2:325-332.

PlaceboPlacebo

6.25 mg BID6.25 mg BID

BaselineBaseline

12.5 mg BID12.5 mg BID

33––10 10 DaysDays

33––10 10 DaysDays

633633EventsEvents

Visits Every 3Visits Every 3––4 4 MonthsMonths

CarvedilolCarvedilol25 mg BID25 mg BID

Encouraged adjunctive therapy

Receiving ACE inhibitor 48 hrs

Clinically stable, but may have had pulmonary edema or cardiogenic

shock during index infarction

Encouraged adjunctive therapy

Receiving ACE inhibitor 48 hrs

Clinically stable, but may have had pulmonary edema or cardiogenic

shock during index infarction

2121

CAPRICORN:All-Cause Mortality

The CAPRICORN Investigators.The CAPRICORN Investigators.

Lancet Lancet 2001;357:13852001;357:1385--1390.1390.

6,644 patients with LVEF<40% after a MI with or without HF randomized to carvedilol

or placebo for 24 months

0.70.7

0.750.75

0.80.8

0.850.85

0.90.9

0.950.95

11

00 0.50.5 11 1.51.5 22 2.52.5


PlaceboPlacebo

YearsYears

Prop

ortion

Eve

ntPr

opor

tion

Eve

nt-- f

ree

free

n=975n=975

n=984n=984


PostPost--Infarct Survival Control in LV Dysfunction Infarct Survival Control in LV Dysfunction (CAPRICORN)(CAPRICORN)

HR = 0.77 (0.60HR = 0.77 (0.60--0.98)0.98)p = 0.031p = 0.031

2222

Heart Failure: Is There Class Effect?

MERIT-HF. Lancet 1999;353:2001-2007; CIBIS-II. Lancet 1999;353:9-13; Packer M, et al. N Engl J Med 2001;344:1651-1658; BEST. N Engl J Med 2001;344:1659-1667.

MERITMERIT--HF. HF. LancetLancet 1999;353:20011999;353:2001--2007; CIBIS2007; CIBIS--II. II. LancetLancet 1999;353:91999;353:9--13; Packer M, et 13; Packer M, et al. al. N N EnglEngl J Med J Med 2001;344:16512001;344:1651--1658; BEST. 1658; BEST. N N EnglEngl J MedJ Med 2001;344:16592001;344:1659--1667.1667.

Relative risk and 95% confidence intervalsRelative risk and 95% confidence intervalsRelative risk and 95% confidence intervals

AnnualMortalityAnnualAnnual

MortalityMortalityBEST (n=2708)Placebo

17.0%

Bucindolol

15.0%

CIBIS-II (n=2647)Placebo

13.2%

Bisoprolol

8.8%

MERIT-HF (n=3991)Placebo

11.0%Metoprolol

succinate

7.2%

COPERNICUS (n=2289)Placebo

18.5%

Carvedilol

11.4%

BEST BEST (n=2708)(n=2708)PlaceboPlacebo

17.0%17.0%

BucindololBucindolol

15.0%15.0%

CIBISCIBIS--II II (n=2647)(n=2647)PlaceboPlacebo

13.2%13.2%

BisoprololBisoprolol

8.8%8.8%

MERITMERIT--HF HF (n=3991)(n=3991)PlaceboPlacebo

11.0%11.0%MetoprololMetoprolol

succinatesuccinate

7.2%7.2%

COPERNICUS COPERNICUS (n=2289)(n=2289)PlaceboPlacebo

18.5%18.5%


11.4%11.4%

000 0.250.250.25 0.50.50.5 0.750.750.75 1.01.01.0 1.251.251.25 1.51.51.5 1.751.751.75 2.02.02.0

Mean

Risk

PFollow-up

Reduction

ValueMeanMean

RiskRisk

PPFollowFollow--upup

ReductionReduction

ValueValue

10.4 mo

35%

p =.001410.4 mo10.4 mo

35%35%

p =.0014p =.0014

12 mo

34%

p =.006212 mo12 mo

34%34%

p =.0062p =.0062

15 mo

34%

p =.000115 mo15 mo

34%34%

p =.0001p =.0001

24 mo

10%

p =. 1024 mo24 mo

10%10%

p =. 10p =. 10

2323

Study of Effects of Study of Effects of NebivololNebivolol Intervention on Outcomes and Intervention on Outcomes and

RehospitalizationRehospitalization in Seniors in Seniors

with Heart Failurewith Heart Failure ((SENIORSSENIORS) )

European Society of Cardiology European Society of Cardiology Congress 2004Congress 2004

2424

SENIORS Study

100100

9090

8080

7070

6060

5050

100100

9090

8080

7070

6060

505000 66 1212 1818 2424 3030 00 66 1212 1818 2424 3030

HR 0.86 (0.74HR 0.86 (0.74––0.99) 0.99) P = 0.039P = 0.039

Time (months)Time (months)

AllAll--cause Mortality or CV Hospital cause Mortality or CV Hospital Admission (Primary Outcome)Admission (Primary Outcome)

NebivololNebivolol

Time (months)Time (months)

AllAll--cause Mortality cause Mortality (Main Secondary Outcome)(Main Secondary Outcome)

HR 0.88 (0.71HR 0.88 (0.71––1.08) 1.08) P = 0.214P = 0.214

PlaceboPlacebo

EventEvent--

free free

survival survival (%)(%)

NebivololNebivolol

PlaceboPlacebo

FlatherFlather

MD, et al. MD, et al. EurEur Heart J Heart J 2005; 26:2152005; 26:215--225.225.

2128 patients 2128 patients ≥≥

70 years 70 years heart failure historyheart failure history (admission < 1 year or known EF (admission < 1 year or known EF ≤≤35%) 35%) to to nebivololnebivolol, titrated to 10 mg QD, or placebo, titrated to 10 mg QD, or placebo

Median 21 monthsMedian 21 months

2525

SexualSexual DysfunctionDysfunction

Decreased blood flow in the Corpora Decreased blood flow in the Corpora CavernosaCavernosa

due to Vasoconstrictiondue to Vasoconstriction

2727

Effect of Effect of NebivololNebivolol

and and MetoprololMetoprolol on Sexual Function: IIEFon Sexual Function: IIEF

2828

28

Nebivolol

and erectile function Prevalence of erectile dysfunction

Doumas M, et al. Asian J Androl 2006; 8:177-82.

Before nebivolol After nebivololSevere

Moderate

Mild

None

Severity of ED

9% 59%

5%

27%34%

18%30%

18%

44 patients treated previously with beta-blockers switched to nebivolol

2929

Metabolic ChangesMetabolic Changes

Increased insulin resistanceIncreased insulin resistance

Lipid Lipid mmetabolismetabolism

3030

IncreasedIncreased InsulinInsulin

ResistanceResistance

Vasoconstriction causes decrease in Vasoconstriction causes decrease in micromicro--vascular surface area invascular surface area in

skeletal skeletal

muscle causing reduction in the insulinmuscle causing reduction in the insulin-- mediated glucose entry and metabolism.mediated glucose entry and metabolism.

3131

2,792,67

2,29

2,83

0

0,5

1

1,5

2

2,5

3

Baseline Month 6Baseline Month 6NebivololNebivolol

5 mg (n=37)5 mg (n=37)Baseline Month 6Baseline Month 6

MetoprololMetoprolol

100 mg (n=35)100 mg (n=35)

P=0.008

P=0.003

P=NS

Effect of Nebivolol

and Metoprolol on Insulin Resistance

Mea

n M

ean

insu

lin r

esista

nce

by H

OM

Ainsu

lin r

esista

nce

by H

OM

A(( m

d/dL

md/

dLx

IU/

x IU

/ mL

mL ))

Baseline SBP/BP was 153/92 mm Hg and 155/95 mm Hg in the Baseline SBP/BP was 153/92 mm Hg and 155/95 mm Hg in the nebivololnebivolol

and and metroprololmetroprolol

groups, respectively. Following groups, respectively. Following 6 months of therapy. BP was 131/79 mm Hg and 129/82 mm Hg in the6 months of therapy. BP was 131/79 mm Hg and 129/82 mm Hg in the

nebivololnebivolol

and and metroprololmetroprolol

groups, respectively. groups, respectively. HOMA=homeostasis model assessment insulin resistance.HOMA=homeostasis model assessment insulin resistance.CelikCelik

T et al. T et al. J J HypertensHypertens 2006;24:5912006;24:591--596596

3232

Insulin Resistance

-12,2

-21,6-25

-20

-15

-10

-5

0

5

Nebivolol2.5-5 mg QD

Atenolol50-100 mg QD

Perc

enta

ge C

hang

e

p<0.01p<0.01

PoirerPoirer

L, et al. L, et al. J J HypertensHypertens 2001;19:14292001;19:1429--1435.1435.

Insulin Sensitivity IndexInsulin Sensitivity Index

3636--week Randomized, Doubleweek Randomized, Double--blind Crossover Designblind Crossover Design(n = 25)(n = 25)

3333

Objective:

Compare effects of -blockers with different pharmacologic properties on glycemic

and metabolic control in patients

with diabetes and hypertension receiving RAAS blockade

Participants:1235 patients

Treatment:

Carvedilol

6.25 mg to 25 mg bid (n = 498) or Metoprolol

tartrate

50 mg to 200 mg bid

(n = 737) Follow-up:

35 weeks

Objective:Objective:

Compare effects of Compare effects of --blockers with blockers with different pharmacologic properties on different pharmacologic properties on glycemicglycemic

and metabolic control in patients and metabolic control in patients

with diabetes and hypertension receiving with diabetes and hypertension receiving RAAS blockadeRAAS blockade

Participants:Participants:1235 patients 1235 patients

Treatment:Treatment:


6.25 mg to 25 mg bid (n = 6.25 mg to 25 mg bid (n = 498) or 498) or MetoprololMetoprolol

tartratetartrate

50 mg to 200 mg bid 50 mg to 200 mg bid

(n = 737)(n = 737)FollowFollow--up:up:

35 weeks35 weeks

GlycemicGlycemic

Effects in diabetes Mellitus: Effects in diabetes Mellitus: carvedilolcarvedilol--metoprololmetoprolol comparison IN comparison IN hypertensiveshypertensives

studystudy

Bakris

GL, et al. JAMA 2004;292:2227-2236.

GEMINI

3434

Metoprolol tartrate Carvedilol

% (SD) P % (SD) P

HbA1c0.15

(0.04) <0.001 0.02 (0.04) 0.65

Insulin sensitivity –2.0 0.48 –9.1 0.004

GEMINI: Change in HbA1c

and Insulin Sensitivity

EndpointEndpoint(mean (mean ))

BakrisBakris

GL, et al.GL, et al.

JAMAJAMA 2004;292:22272004;292:2227--36.36.

3535

GEMINI GEMINI Progression to Progression to microalbuminuriamicroalbuminuria

Bakris

GL. American Heart Association Scientific Sessions 2004.

Nov 7-10, 2004; New Orleans, LA.

End pointEnd point MetoprololMetoprolol CarvedilolCarvedilol Odds ratio Odds ratio (95% CI)(95% CI)

p p

Progression to Progression to microalbuminuriamicroalbuminuria

(%)(%)

10.310.3 6.46.4 0.60 0.60 0.040.04

3636

LipidLipid MetabolismMetabolism

Decreased Lipoprotein Lipase activity Decreased Lipoprotein Lipase activity results inresults in::

IIncreasedncreased

LDLLDL--cc

andand

Triglyceride levelsTriglyceride levels

DDecreasedecreased

HDLHDL--cc..

3737

0

50

100

150

200Baseline Endpoint

mg/

mg/

dLdL

LDL (mean)LDL (mean) HDL (mean)HDL (mean) TriglyceridesTriglycerides(median)(median)

Nebivolol: Effect on Lipid LevelsPooled Analysis of the Three Pooled Analysis of the Three MonotherapyMonotherapy

US Registration TrialsUS Registration Trials

1.1.Registration trials. Data on file, Forest Laboratories, Inc. NewRegistration trials. Data on file, Forest Laboratories, Inc. New

York, NYYork, NY2.2.NebivololNebivolol

package insert. New York, NY. Forest Laboratories, Inc; 2007package insert. New York, NY. Forest Laboratories, Inc; 2007

3838

VasodilatingVasodilating Beta BlockersBeta Blockers

Improved EfficacyImproved Efficacy

in CHFin CHF

in Elderly and Obese Patientsin Elderly and Obese Patients

3939

SSiigngniiffiicant cant NNoteote

1/3 of1/3 of

heartheart--failure patients are failure patients are

receiving BB in clinical practice, because receiving BB in clinical practice, because clinical trials have generally included clinical trials have generally included younger patients (average age 61), younger patients (average age 61),

HoweverHowever

the average age of heartthe average age of heart--

failure patients in the real world was failure patients in the real world was 76. 76.

4040

Elderly PatientsElderly Patients

Decreased density of Decreased density of ßß receptors receptors results in decreased efficacy in the results in decreased efficacy in the elderly.elderly.

VasodilatingVasodilating

BB do not just work by BB do not just work by

blocking the blocking the ßß rreceptorseceptors..

4242

Obese patientsObese patients

Traditional Beta Blockers results in Traditional Beta Blockers results in 1.2 Kg/Yr weight gain due to reduced 1.2 Kg/Yr weight gain due to reduced resting energy expenditure, and resting energy expenditure, and thermogenesisthermogenesis

(by as much as 10% in (by as much as 10% in

some trials).some trials).

4343

-4,8

-9,3-9,9

-3,6

-9,9-10,9

-10,3 -10,7-12

-10

-8

-6

-4

-2

0

DBP SBP

Mea

n M

ean ∆∆

in B

P in B

P vsvs

base

line

(mm H

g)ba

selin

e (m

m H

g)NN

9292

189189

188188

196196Baseline DBP (mm Hg)Baseline DBP (mm Hg)

100.6100.6

99.999.9

100.3100.3

101.4101.4Baseline SBP (mm Hg)Baseline SBP (mm Hg)

151.4151.4

151.7151.7

154.2154.2

156.4156.4

•Obesity defined as body mass index >30 kg/m2. •Data on file, Forest Laboratories, Inc. New York, NY

Placebo DBP Placebo SBPPlacebo DBP Placebo SBP

DoseDose

PlaceboPlacebo

5 mg5 mg

10 mg10 mg

20 mg20 mg

Efficacy of Efficacy of NebivololNebivolol

in Obesein Obese Patients:Patients:

4444

2006 AACE Hypertension

Guidelines►

ß-blocker use recommended as 2nd

or 3rd

line

in hypertension Because the major adverse effects of BBs

may be

mediated by peripheral vasoconstriction and increasing insulin resistance, the use of the new third-generation ß-blockers (such as nebivolol)

or drugs that block both

α

and ß

receptors (such as carvedilol) may prove to be particularly beneficial. These agents cause vasodilatation and an increase in insulin sensitivity.

►►

ßß--blocker use recommended as 2blocker use recommended as 2ndnd

or 3or 3rdrd

line line in hypertensionin hypertensionBecause the major adverse effects of Because the major adverse effects of BBsBBs

may be may be

mediated by peripheral vasoconstriction and increasing mediated by peripheral vasoconstriction and increasing insulin resistance, the use of the insulin resistance, the use of the new thirdnew third--generation generation ßß--blockers (such as blockers (such as nebivololnebivolol))

or drugs that block both or drugs that block both

αα

and and ßß

receptors (such as receptors (such as carvedilolcarvedilol) may prove to be ) may prove to be particularly beneficial. particularly beneficial. These agents cause These agents cause vasodilatation and an increase in insulin sensitivity.vasodilatation and an increase in insulin sensitivity.

AACE Hypertension Task Force. AACE Hypertension Task Force. EndocrEndocr

PractPract. 2006;12:193. 2006;12:193--222222

4545

Summary

-blockers are a diverse class of drugs

They differ in their indications and their effectiveness for various disorders

Selective, vasodilatory

-blockers are:

●

Indicated for hypertension

●

Proven for heart failure and myocardial infarction

●

Offer advantages in patients with diabetes mellitus

●

Are well tolerated

--blockers are a diverse class of drugsblockers are a diverse class of drugs

They differ in their indications and their They differ in their indications and their effectiveness for various disorderseffectiveness for various disorders

Selective, Selective, vasodilatoryvasodilatory

--blockers are: blockers are:

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Indicated for hypertensionIndicated for hypertension

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Proven for heart failure and myocardial Proven for heart failure and myocardial infarctioninfarction

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Offer advantages in patients with diabetes Offer advantages in patients with diabetes mellitusmellitus

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Are well toleratedAre well tolerated

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