j.r.g. juanatey c.h.u.santiago josé r. gonzález juanatey Área cardiovascular. hospital clínico...

J.R.G. JUANATEY C.H.U.Santiago

José R. González JuanateyÁrea Cardiovascular. Hospital Clínico Universitario de

Santiago de Compostela

1

1

Estudio SHARPImplicaciones en la Prevención 2ª de la

Cardiopatía Isquémica


Ezetimibe 2011

Cuestiones pendientes

Seguridad

Nefroprotección

Eficacia


EU, Total Cholesterol Goal

EUROASPIRE III

% patients in 2P Total cholesterol >4.5 mMol/L (175

mg/dL)


Kastelein J et al. N Engl J Med 2008;358:1431-1443 Taylor A et al. N Engl J Med 2009;361:2113-2122

Intima-Media Thickness of the Carotid Artery during 24 and 14 Months of Therapy

ENHANCE-Trial

ARBITER-6 HALTS


Ezetimibe

“During the trial, investigators reported an increased number of cancers and cancer-related deaths in patients using Vytorin compared to placebo. Cancer was reported in 105 patients (11.1%) in the Vytorin group and in 70 patients (7.5%) in the placebo group. The number of deaths from cancer was also higher in the Vytorin group, with 39 deaths compared to 23 deaths in the placebo group.

A large body of long-term clinical data indicates that simvastatin is not associated with an increased risk of cancer, but long-term clinical data on ezetimibe is insufficient to definitely rule out a cancer risk at this time.”

FDA Statement 22. 12. 2009


Alternativas en práctica clínica


de qué estamos pendientes…


Ezetimibe 2011


Seguridad

Nefroprotección

Eficacia


0 1 2 3 4 5 Años de seguimiento

0

5

10

15

20

25

Porc

enta

je d

e ev

ento

s (%

)

Ratio de riesgo 0.83 (0.74 – 0.94) Logrank 2P=0.0022

Placebo

Eze/simv

SHARP: Principales eventos isquémicos


CTT: Efectos sobre los eventos isquémicos

Redu

cció

n de

ries

go re

lativ

ode

eve

ntos

isqu

émic

os (9

5% C

I)

0%

5%

10%

15%

20%

25%

30% Estatinas vs control(21 estudios)

Tratamientohipolipemiante

intensivovs

convencional(5 estudios)

SHARPSHARP32 mg/dL32 mg/dL

0 20 4010 30Diferencia media de cLDL

entre los grupos tratados (mg/dL)

SHARP17% de

reducción de riesgo


Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis

Rossebo AB et al. N Engl J Med 2008;359

Kaplan–Meier Curves for Primary and Secondary Outcomes and Death

Ischemic Cardiovascular Events Death from Any cause

Hazard ratio, 0.78

P=0.02

Simvastatin plus ezetimible

Placebo

Years in Study

Per

cen

tag

e o

f P

atie

nts

Hazard ratio, 1.04

P=0.80


Placebo

Years in Study

Per

cen

tag

e o

f P

atie

nts

No. at Risk


917 867 823 769 76

Placebo 898 838 788 729 76

No. at Risk


930 912 884 855 89

Placebo 916 890 865 835 94


-10

0

10

20

30

40

50

0,5 1,0 1,5 2,0

-10

0

10

20

30

40

50

0,5 1,0 1,5 2,0

Red

ucc

ión

Pro

po

rcio

nal

en

Ín

dic

e d

e E

nfe

rmed

ades

(S

E)

Enfermedades Coronarias Mayores Enfermedades Vasculares Mayores

Reducción colesterol LDL (mmol/L)

Meta-análisis HipolipemiantesEz/Sim - Eficacia

SPARCL-A

-1.58

-35

SPARCL-A

-1.58

-20

-16Ictus

Lancet 2006, 2010

SHARP Ez/Sm (16.1%)

SHARP Ez/Sm (26.3%)


CTT: Efectos sobre los eventos isquémicos CV Protection in CKD Pt

Redu

cció

n de

ries

go re

lativ

ode

eve

ntos

isqu

émic

os (9

5% C

I)

0%

5%

10%

15%

20%

25%

30% Estatinas vs control(21 estudios)

Tratamientohipolipemiante

intensivovs

convencional(5 estudios)

SHARPSHARP32 mg/dL32 mg/dL

0 20 4010 30Diferencia media de cLDL

entre los grupos tratados (mg/dL)

SHARP17% de


Baseline:

CT 189+45 mg/dl

LDL-C 108+34 mg/dl

AURORA4% de




SHARP


Ezetimibe 2011


Seguridad

Nefroprotección

Eficacia


SHARP: Incidencia de Cáncer

0 1 2 3 4 5 0

5

10

15

20

25

Porc

enta

je d

e pa

cien

tes

que

desa

rrol

lan

cáce

r (%

)

Placebo Eze/simv

Risk ratio 0.99 (0.87 – 1.13) Logrank 2P=0.89

Años de seguimiento


SHARP: SeguridadSHARP: Seguridad

Eze/simv(n=4650)

Placebo(n=4620)

Miopatía

CK >10 x y ≤40 x ULN 17 (0.4%) 16 (0.3%)

CK >40 x ULN 4 (0.1%) 5 (0.1%)

Hepatitis 21 (0.5%) 18 (0.4%)

Aumento continuado ALT/AST >3x ULN 30 (0.6%) 26 (0.6%)

Complicaciones por cálculos biliares 85 (1.8%) 76 (1.6%)

Otras hospitalizaciones por cálculos biliares

21 (0.5%) 30 (0.6%)

Pancreatitis sin cálculos biliares 12 (0.3%) 17 (0.4%)


Ezetimibe

“During the trial, investigators reported an increased number of cancers and cancer-related deaths in patients using Vytorin compared to placebo. Cancer was reported in 105 patients (11.1%) in the Vytorin group and in 70 patients (7.5%) in the placebo group. The number of deaths from cancer was also higher in the Vytorin group, with 39 deaths compared to 23 deaths in the placebo group.

A large body of long-term clinical data indicates that simvastatin is not associated with an increased risk of cancer, but long-term clinical data on ezetimibe is insufficient to definitely rule out a cancer risk at this time.”?

FDA Statement 22. 12. 2009


Ezetimibe 2011


Seguridad

Nefroprotección

Eficacia


Risk ratio & 95% CIEventos PlaceboEze/simv

Eze/simvmejor

Placebomejor

(n=3130)(n=3117)

Evento renal principalEstadío final de Enfermedad Renal (ESRD)

1057 (33.9%) 1084 (34.6%) 0.97 (0.89-1.05)

Eventos renales secundariosESRD o muerte 1477 (47.4%) 1513 (48.3%) 0.97 (0.90-1.04)

ESRD o 2x Cr 1190 (38.2%) 1257 (40.2%) 0.94 (0.86-1.01)

0.6 0.8 1.0 1.2 1.4

SHARP: Datos sobre parámetros Renales



SHARP


Ezetimibe 2011


Seguridad

Nefroprotección

Eficacia

j.r.g. juanatey c.h.u.santiago josé r. gonzález juanatey Área cardiovascular. hospital clínico...

Documents