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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
J.R.G. JUANATEY C.H.U.Santiago
Ezetimibe 2011
Cuestiones pendientes
Seguridad
Nefroprotección
Eficacia
J.R.G. JUANATEY C.H.U.Santiago
J.R.G. JUANATEY C.H.U.Santiago
EU, Total Cholesterol Goal
EUROASPIRE III
% patients in 2P Total
cholesterol >4.5 mMol/L (175
mg/dL)
J.R.G. JUANATEY C.H.U.Santiago
J.R.G. JUANATEY C.H.U.Santiago
J.R.G. JUANATEY C.H.U.Santiago
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
J.R.G. JUANATEY C.H.U.Santiago
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
J.R.G. JUANATEY C.H.U.Santiago
Alternativas en práctica clínica
J.R.G. JUANATEY C.H.U.Santiago
de qué estamos pendientes…
J.R.G. JUANATEY C.H.U.Santiago
Ezetimibe 2011
Cuestiones pendientes
Seguridad
Nefroprotección
Eficacia
J.R.G. JUANATEY C.H.U.Santiago
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
J.R.G. JUANATEY C.H.U.Santiago
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
J.R.G. JUANATEY C.H.U.Santiago
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
J.R.G. JUANATEY C.H.U.Santiago
-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%)
J.R.G. JUANATEY C.H.U.Santiago
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
reducción de riesgo
Baseline:
CT 189+45 mg/dl
LDL-C 108+34 mg/dl
AURORA 4% de
reducción de riesgo
J.R.G. JUANATEY C.H.U.Santiago
Alternativas en práctica clínica
SHARP
J.R.G. JUANATEY C.H.U.Santiago
Ezetimibe 2011
Cuestiones pendientes
Seguridad
Nefroprotección
Eficacia
J.R.G. JUANATEY C.H.U.Santiago
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
J.R.G. JUANATEY C.H.U.Santiago
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%)
J.R.G. JUANATEY C.H.U.Santiago
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
J.R.G. JUANATEY C.H.U.Santiago
Ezetimibe 2011
Cuestiones pendientes
Seguridad
Nefroprotección
Eficacia
J.R.G. JUANATEY C.H.U.Santiago
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
J.R.G. JUANATEY C.H.U.Santiago
Alternativas en práctica clínica
SHARP
J.R.G. JUANATEY C.H.U.Santiago
Ezetimibe 2011
Cuestiones pendientes
Seguridad
Nefroprotección
Eficacia
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