estudio sharp. implicaciones en la prevención secundaria de la … · 2014. 10. 23. · j.r.g....

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

José R. González Juanatey Área Cardiovascular. Hospital Clínico Universitario de Santiago de

Compostela

1

1

Estudio SHARP

Implicaciones 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

Red

ucc

ión

de

rie

sgo

rel

ativ

o

de

eve

nto

s is

qu

ém

ico

s (9

5%

CI)

0%

5%

10%

15%

20%

25%

30% Estatinas vs control

(21 estudios) Tratamiento

hipolipemiante intensivo

vs convencional (5 estudios)

SHARP 32 mg/dL

0 20 40 10 30 Diferencia media de cLDL

entre los grupos tratados (mg/dL)

SHARP 17% 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

Perc

en

tag

e o

f P

ati

en

ts

Hazard ratio, 1.04

P=0.80

Simvastatin plus

ezetimible

Placebo

Years in Study

Perc

en

tag

e o

f P

ati

en

ts

No. at Risk

Simvastatin plus

ezetimible 917 867 823 769 76

Placebo 898 838 788 729 76

No. at Risk

Simvastatin plus

ezetimible 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

Re

du

cció

n P

rop

orc

ion

al

en

Ín

dic

e

de E

nfe

rmed

ad

es (

SE

)

Enfermedades Coronarias Mayores Enfermedades Vasculares Mayores

Reducción colesterol LDL (mmol/L)

Meta-análisis Hipolipemiantes Ez/Sim - Eficacia

SPARCL-A

-1.58

-35

SPARCL-A

-1.58

-20

-16 Ictus

Lancet 2006, 2010

SHARP

Ez/Sm

(16.1%)

SHARP

Ez/Sm

(26.3%)


CTT: Efectos sobre los eventos isquémicos

CV Protection in CKD Pt R

edu

cció

n d

e r

iesg

o r

elat

ivo

d

e e

ven

tos

isq

ué

mic

os

(95

% C

I)

0%

5%

10%

15%

20%

25%

30% Estatinas vs control

(21 estudios) Tratamiento

hipolipemiante intensivo

vs convencional (5 estudios)

SHARP 32 mg/dL

0 20 40 10 30 Diferencia media de cLDL

entre los grupos tratados (mg/dL)

SHARP 17% de


Baseline:

CT 189+45 mg/dl

LDL-C 108+34 mg/dl

AURORA 4% 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 p

acie

nte

s q

ue

des

arro

llan

các

er (

%)

Placebo

Eze/simv

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

Años de seguimiento


SHARP: 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% CI Eventos Placebo Eze/simv

Eze/simv mejor

Placebo mejor

(n=3130) (n=3117)

Evento renal principal

Estadío final de Enfermedad Renal (ESRD)

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

Eventos renales secundarios

ESRD 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

estudio sharp. implicaciones en la prevención secundaria de la … · 2014. 10. 23. · j.r.g....

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