Buc, 15.06.

2013

Betablocantele in terapeutica: sinoptic 2013

Marius VINTILA

Clinica de Medicina Interna si Cardiologie Spit. Urgenta Sf. Pantelimon- Bucuresti

Beneficiile cv ale BB
Indicatie Clasa Evid A ControlulTA TA I Controlul A I A IMA oral, toti fara ci I A Post IMA, toti fara ci, indefinit I A I B Angina I B Angina Instabila Instabila I A Angina I A Angina Stabila Stabila antec. antec. IMA IMA I C I C fara fara antec. antec. IMA IMA I A Insuf. I A Insuf. Cardiaca Cardiaca sistolica sistolica cls cls I-IV I-IV I C IIa C distolica distolica IIa C Aritmii: TS I C TPSV I/IIa A/C FA, FlutterA (control frecv) I A Ventriculare I C Disectia de aorta I

HTA CI ICcr

M. VINTILA 2013

Contraindicatii BB
CONTRAINDICATII BPOC NU e c.i. pentru BB - ASTMUL BRONSIC cazuri cu tolerabilitate limitata - AV < 50/min., blocuri AV - hTA SEVERA (soc, < 90 simptomatica) - ischemia periferica critica

Bradicardizare: efecte favorabile

Beautiful-brat Pbo

cohorta 2230 danezi t=10 ani

A reduction of 10 beats/min/day saves ~5kg of ATP a day!

BB in BPOC: RR mortalitate cu 30% RR exacerbari cu 27% mai ales b1 selective indiferent de boala CV
M. VINTILA 2013

DZ si BB DZ NU e c.i. pentru BB

x2-x4 ca non-diabetici mai ales T2DM severitate, risc vital

DZ+CI(post IM) si DZ+ICcr indicatie absoluta

DZ+HTA izolata (sigur) mai bine nu

risc de DZ + HTA izolata abtinere

GRADE Beta-blockers and thiazide diuretics are not recommended in hypertensive patients with multiple III A Strong metabolic risk factors increasing the risk of new-onset diabetes.
Perk J et al. Eur Heart J, doi:10.1093/eurheartj/ehs092, 03.05.2012
M. VINTILA 2013

BB: efecte nedorite risc metabolic intoleranta la efort membre reci disfunctie erectila astenie tulburari de somn depresie

limitate prin selectivitate

Marele Bau-Bau: efect inotrop negativ

cord normal functional rezerva contractila x10-20 cord insuficient administrare brusca nociva administrare progresiva benefica
M. VINTILA 2013

Survival
1.0

CIBIS-II
Bisoprolol

0.8

Placebo
0.6

Reducerea riscului = 34% P < 0.0001

Mortality%
20

0 0 200 400 600 BBlocada in ICcr: Time after inclusion (days) mortalitate generala

800

MERIT-HF
Placebo

CIBIS-II Investigators. 1999

15

Metoprolol CR/XL
10

RRR = 34% P = 0.0062

0 3 6 9 12 15 18 21 Luni

The MERIT-HF Study Group. 1999

M. VINTILA 2013

ANM: indicatiile inregistrate ale BB in Ro

BB
Indicatia HTA Aten Beta Biso + + (prev) + + C + + + + + (adj) + + succ FE35 + + +
M. VINTILA 2013

M + +

N +

P +

Angina stabila
Angina instabila IMA

ICcr
Aritmii Tulb.func.cardiace Migrena (prof)

+ >70

I. BB in HTA

M. VINTILA 2013

BB ca terapie initiala in HTA

Bolnavul hipertensiv cu indicatie de BB:

initial HTA + CI HTA + ICcr HTA + DZ HTA + FA HTA + hipertiroidism HTA + glaucom
ulterior

toti necontrolatii

M. VINTILA 2013

Care BB in HTA ?

EFECT DE CLASA

selectiv efecte adverse lent o.d. complianta efect remanent rebound la doza sarita nu Atenolol

M. VINTILA 2013

Care BB in HTA ?

pe alese

BETAXOLOL BISOPROLOL

francez

german
englez italian

METOPROLOL
NEBIVOLOL

M. VINTILA 2013

Care BB in HTA ?

dar
HTN was found in: 73% of those with CHD 71% in those with CHF
Wong ND et al. Arch Intern Med 2007;167:2394

Metoprolol succinat situatia standard Situatii speciale

BAP membre reci disfunctie erectila
M. VINTILA 2013

BB selectiv vasodilatator

Nebivolol

II. BB in cardiopatia ischemica

M. VINTILA 2013

Locul betablocantelor in CI.

ANGINA PECTORALA cronica, stabila SINDR. CORONARIENE ACUTE IM angina instabila

bblocant
Simptome Morbiditate Mortalitate

FORME IN CARE DUREREA NU E SIMPTOM DOMINANT cardiomiopatia ischemica IC. insuf.mitrala prin disfunctie de pilier Control av aritmii (FA, blocuri AV, BRS) moartea subita cardiaca Risc
M. VINTILA 2013

Betablocantele in IMA ACTIUNI IN ACUT

av., DC, TA titrul AGL consum O2 oxidare ciclul Krebs contractilitate wall stress efect antiaritmic durere anginoasa dimensiunea infarctului aritmii ischemia recurenta ruptura miocardica

Efect : mortalitate pe termen scurt cu 13%

M. VINTILA 2013

Betablocantele in IMA ACTIUNI IN CRONIC

dimensiunea infarctului reinfarctarea ischemia recurenta aritmii moartea subita cardiaca previn instalarea IC progresia IC

Efect : mortalitate pe termen lung cu 23%

M. VINTILA 2013

Betablocantele in A.STABILA
consum O2 av. 50-60/min.= obiectiv terapeutic contractilitate postsarcina vasoconstrictie de efort efect antiaritmic moartea subita controleaza aritmii ischemice previn IM si reIM intarzie instalarea IC

TRATEAZA SIMPTOME efect antianginos REDUC MORTALITATE SI MORBIDITATE

INDICATIE DE CLASA I
M. VINTILA 2013

Betablocantele in A.STABILA CANDIDATUL CU BENEFICIU MAXIM relatie proeminenta atac anginos efort antecedent de IM HTA asociata

disfunctie sistolica de VS
IC cls.II-III(IV)

istoric de aritmii supra sau ventriculare

anxietate asociata
Braunwald E. Heart Disease, ed.6, Saunders, 2001, p.1293
M. VINTILA 2013

Care betablocante in CI. ? fara ASI b1 selective cu 1-2 administrari / zi

OPINIE M. V. CI stabila Metoprolol succinat CI instabila oral/iv Metoprolol succinat

EFECT DE CLASA NU ATENOLOL

post IM precoce standard Metoprolol succinat + disfunctie VS Carvedilol (CAPRICORN)

M. VINTILA 2013

III. BB in Insuficienta Cardiaca

M. VINTILA 2013

CHF Treatment
CONTROL VOLUME
ACEi (ARB) REDUCE MORTALITY Betablocker Aldosterone antagonist

Diuretic

Implantable cardioverter-defibrillator Resynchronization

Digoxin

TREAT RESIDUAL SYMPTOMS

M. VINTILA 2013

Terapie farmacologica in IC : principalele deziderate

Mecanisme logice Reducere mortalitate

Efecte Reducere benefice Reducere simptome asociate spitalizari Rol in DVS Date concordante asimptomatica pentru multipli Tolerabilitate agenti din clasa / efecte Relatie Date despre adverse dozainteractiuni efect medicamentoase Efect la pacienti severi (NYHA IV)
M. VINTILA 2013

Terapie farmacologica in IC: B-Blocante

Mecanisme logice Reducere mortalitate Efecte benefice asociate Reducere simptome

Reducere spitalizari

Rol in DVS asimptomatica

Date concordante pentru multipli agenti din clasa

Relatie dozaefect

Tolerabilitate / efecte adverse Date despre interactiuni medicamentoase

Efect la pacienti severi (NYHA IV)

M. VINTILA 2013

Terapie farmacologica in IC
BETA-BLOCANTELE
Mecanisme logice Reducere mortalitate Efecte benefice asociate Date concordante pentru multipli agenti din clasa Relatie dozaefect Reducere simptome
Mecanisme logice

IECA
Reducere mortalitate Efecte benefice asociate Date concordante pentru multipli agenti din clasa Relatie dozaefect Reducere simptome

Reducere spitalizari
Rol in DVS asimptomatica

Rol in DVS asimptomatica

Reducere spitalizari

Tolerabilitate / efecte adverse Date despre interactiuni medicamentoase

Date despre interactiuni medicamentoase Efect la pacienti severi (NYHA IV)

Tolerabilitate / efecte adverse

Efect la pacienti severi (NYHA IV)

DIGITALICELE
Mecanisme logice Reducere mortalitate Efecte benefice asociate Reducere simptome

DIURETICELE
Mecanisme logice
Reducere spitalizari

Reducere mortalitate Efecte benefice asociate Date concordante pentru multipli agenti din clasa Relatie dozaefect Reducere simptome

Reducere spitalizari

Rol in DVS asimptomatica

Date concordante pentru multipli agenti din clasa Relatie dozaefect

Rol in DVS asimptomatica

Tolerabilitate / efecte adverse

Date despre interactiuni medicamentoase Efect la pacienti severi (NYHA IV)

Date despre interactiuni medicamentoase Efect la pacienti severi (NYHA IV)

Tolerabilitate / efecte adverse

M. VINTILA 2013

Mortality%
20

MERIT-HF
Placebo

15

Metoprolol CR/XL
10

RRR = 34% P = 0.0062

0 3 6 9 12 15 18 21 Luni

The MERIT-HF Study Group. 1999

bBlockade in CHF: Survival All-cause mortality 1.0

0.8

CIBIS-II
Bisoprolol Placebo

0.6 0 0

Reducerea riscului = 34% P < 0.0001

200 400 600 800

Time after inclusion (days)

CIBIS-II Investigators. 1999
M. VINTILA 2013

Putem compara studiile de ICCr ?

Clinical characteristics CIBIS II Biso or Placebo n = 2647 61 US Carved Carvedilol or Placebo n = 1105 58 COPERNIC Carvedilol or Placebo n = 2289 63 MERIT-HF MetoCR/XL or Placebo n = 3991 64 22 SENIORS Nebivolol or Placebo n = 2128 76 37

Study
Age (mean, y) Women (%)

RR

CI 95%
20

RRR %

SENIORS 19 EF (mean, %) 27 Age<75, LVEF 35%

Ischaemic etio (%)
BP: Systolic

0.62 23
48

23

0.43-0.89 20

28 Study population

38% 36
68

10 Study population 1 11617 12319 CIBIS II 0.66 0.54-0.81 9 in other BB trials Diastolic 7211 7611 8 7 Prevalence of CHF Comorbidities (%) 6 by Age and2 Sex in NHANES MERIT-HF 0.66 0.53-0.81 Hypertension na 44 5 Men Women 4 Diabetes na na 26 24 3 Pbo ann 13.2 na 19.7 11.0 3 2 mortality COPERNICUS 0.65 0.52-0.81 1 MERIT-HF Study Group Am J Cardiol 1997;80(9B):54J-8J CIBIS II Investigators. Lancet 1999, 353: 913 0 MD Flather Eur Heart J 2005;26:215-225 M Packer et al. N Engl J Med 1996;334:1349-55.) 20-24 25-34 35-44 45-54 55-64 65-74 >74 M Packer et al. N Engl J Med 2001;344:1651-8.) Percentage (%)

50

67 in SENIORS 66

34%

34% 61
26 10.4 35%

M. VINTILA 2013

Situatie particulara: ICcr foarte severa

M. VINTILA 2013

Betablocante in IC : doze uzuale zilnice Meto prolol

1. INITIAL 2. LA 2 SAPT. 3. LA 4 SAPT.

Carve dilol

Nebi volol
1,25 2,5 5

Biso prolol
1,25 2,5 5

12,5 2x3,125 25 50 2x6,25 2x12,5

4. FINAL

100

2x25

10

5-10

ASOCIEREA CU DIGITALA SAU AMIODARONA REDUCE DOZA FINALA LA JUMATATE

M. VINTILA 2013

Care betablocante in ICcr. ?

standard: varstnici:

Metoprolol succinat Nebivolol

gravi(NYHA IV): Carvedilol

M. VINTILA 2013

Mortality%
20

MERIT-HF
Placebo

15

Metoprolol CR/XL
10

=
RRR = 34% P = 0.0062
0 3 6 9 12 15 18 21 Luni

The MERIT-HF Study Group. 1999

De ce M succinat ?

C=M succinat C>M tartrat

M suc>M tar
M. VINTILA 2013

Mesaje de luat acasa

BB de prima intentie in HTA: efect de clasa contraindicate la risc DZ standard: Metoprolol succinat tulb perfuzie periferica: Nebivolol
BB in CI indicate in toate formele clinice standard: Metoprolol succinat

BB in ICcr. prima linie terapeutica standard: Metoprolol succinat varstnici: Nebivolol gravi(NYHA IV): Carvedilol
M. VINTILA 2013