Manejo del Síndrome Coronario Agudo en Poblaciones Especiales

Manejo del Síndrome Coronario Agudo en Poblaciones Especiales

Tratamiento prolongado
antiagregante en subgrupos
de pacientes
José F. Díaz, MD, FESC
Complejo Hospitalario de Huelva
Primary Endpoint
CV Death,MI,Stroke
15
Clopidogrel
CV Death / MI / Stroke
Endpoint (%)
10
12.1 HR 0.81
(0.73-0.90)
P=0.0004
9.9
Prasugrel
5
TIMI Major
NonCABG Bleeds
Prasugrel
Clopidogrel
2.4 HR 1.32
1.8 (1.03-1.68)
P=0.03
0
0 30 60 90
180
Wiviot SD, Braunwald E, McCabe CH et al NEJM 2007
Days
270
360
450
Diabetic Subgroup
N=3146
18
Clopidogrel
17.0
16
CV Death / MI / Stroke
Endpoint (%)
14
12.2
12
HR 0.70
P<0.001
NNT = 46
Prasugrel
10
8
6
TIMI Major
NonCABG Bleeds
4
2
0
Clopidogrel
Prasugrel
0
30 60 90
Wiviot SD, Circulation 2008
Days
180
270
360
2.6
2.5
450
STEMI Cohort
N: 3534
15
Clopidogrel
12.1
CV Death / MI / Stroke
9.9
Endpoint (%)
10
Prasugrel
5
TIMI Major
NonCABG Bleeds
Prasugrel
Clopidogrel
2.4
1.8
0
0 30 60 90
Montalescot et al. Lancet 2009; 373: 723–31
180
Days
270
360
450
TRITON TIMI 38 Net clinical
benefit: Bleeding risk subgroups
Risk (%)
Yes
Prior
stroke/TIA
+54
No
Pint = 0.006
≥75
Age
–1
<75
Weight
Pint = 0.18
<60 kg
Pint = 0.36
Wiviot SD, Braunwald E, McCabe CH et al NEJM 2007
–14
–13
OVERALL
Prasugrel better
–16
+3
≥60 kg
0.5
–16
1
HR
Clopidogrel better
2
Cumulative Incidence (%)
PLATO Study
N: 18.624
Days after randomization
Wallentin L et al. N Engl J Med 2009;361:1045-57.
Mortality reduction in Invasive and
non--invasive treatment strategies
non
James SK et al. BMJ 2011; 342:d3527
Ticagrelor y función renal
Variable primaria compuesta
MuerteCV, IM, Ictus
Variable de Seguridad
James S. Circulation 2010;122:1056–1067.
Población con Ictus/TIA previo
Mortalidad Total
Variable primaria compuesta
MuerteCV, IM, Ictus
HR: 0.62
(95% CI = 0.42–0.91)
HR: 0.87
(95% CI = 0.66–1.13)
Pint = 0.84
Pint = 0.19
HR: 0.81
(95% CI = 0.70–0.95)
HR: 0.84
(95% CI = 0.76–0.93)
HR: 0.99
(95% CI = 0.71–1.37)
---- Clopidogrel
---Ticagrelor
James SK, et al. Circulation. 2012;125:2914-2921
HR: 1.04
(95% CI = 0.95–1.14)
Pint = 0.77
Sangrados
Mayores
PLATO CABG
Mortalidad según días previos de
interrupción de tratamiento
Variable Principal Muerte CV/IM/Ictus
HR: 0.84 (95% CI = 0.60–1.16), p=0.29
Sangrados
Held C, et al. J Am Coll Cardiol 2011;57:672–684.
Subgrupo de Diabéticos (n=4662)
Variable primaria según
presencia de DM
Sangrado según
presencia de DM
James S. Eur Heart J 2010;31:3006–3016.
STEMI-PCI
TRITON STEMI-PCI
Montalescot et al. Lancet 2009; 373: 723-31
PLATO STEMI: All Cause Mortality
K-M Estimated Rate (% Per Year)
7
Clopidogrel
6
6.0
5
4.9
Ticagrelor
4
3
2
1
HR 0.82 (95% CI = 0.68-0.99), p = 0.04
0
0
No. at risk
Ticagrelor
Clopidogrel
1
2
4,201 4,005
4,229 4,029
3
4
3,962
3,989
5
6
7
Months
3,876
3,912
8
3,150
3,195
9
10
2,413
2,471
11
12
1,993
1,980
CI=Confidence Interval; HR=Hazard Ratio; K-M=Kaplan-Meier; PLATO=PLATelet Inhibitiion and Patient Outcomes; STEMI=ST-Elevation Myocardial Infarction
Steg PG, et al. Circulation 2010;122:2131-2141
TRITON-TIMI 38: Mortality in STEMI
5.0
Clopidogrel 4.3%
All Cause Death (%)
4.5
4.0
3.5
3.0
2.5
Prasugrel 3.3%
2.0
1.5
Hazard Ratio, 0.76
(95% CI, 0.54-1.07)
p = 0.11
1.0
0.5
0.0
0 30
90
180
270
360
450
Days from Randomization
Number at Risk:
Prasugrel -
1769 1694
1666
1644
1619
1605
1324
Clopidogrel - 1765 1683
1653
1636
1615
1598
1299
Data on File, Daiichi Sankyo, Inc. and Eli Lilly and Company
CI=Confidence Interval; STEMI=ST-Elevation Myocardial Infarction; TRITON-TIMI=TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN
with Prasugrel Thromobolysis In Myocardial Infarction
Tratamiento en subgrupos
PCI CURE
Definite/Probable ST
Any Stent (N=12.844)
Wiviot SD, Braunwald E, McCabe CH et al NEJM 2007
Definite/Probable ST
Any Stent (N=12.844)
Antman EM. NYHA 2007
Definite Stent
Thrombosis
Safety of Long Term DAPT
5.5% at the
1st month
K-M estimated rate (% per year)
15
Ticagrelor
10
Clopidogrel
11.58
11.20
5
HR 1.04 (95% CI 0.95–1.13), p=0.434
0
0
No. at risk
Ticagrelor 9,235
Clopidogrel 9,186
60
120
180
240
300
360
Days from first IP dose
7,246
7,305
Wallentin L et al. N Engl J Med 2009;361:1045-57.
6,826
6,930
6,545
6,670
5,129
5,209
3,783
3,841
3,433
3,479
Timing of Benefit
Landmark Analysis
Wiviot SD, Braunwald E, McCabe CH et al NEJM 2007
Timing of Benefit
(Landmark Analysis – 30 days)
NNT=70
NNT=227
Antman EM. NYHA 2007; http://circ.ahajournals.org/cgi/content/meeting_abstract/118/18_MeetingAbstracts/S_818-c
Primary efficacy endpoint over time
(composite of CV death, MI or stroke)
8
6
Clopidogrel
4
5.43
4.77
Ticagrelor
2
HR 0.88 (95% CI 0.77–1.00), p=0.045
0
0
10
20
30
Cumulative incidence (%)
Cumulative incidence (%)
8
6.60
Clopidogrel
6
5.28
4
Ticagrelor
2
HR 0.80 (95% CI 0.70–0.91), p<0.001
0
31
Days after randomisation
90
150
210
270
330
Days after randomisation*
No. at risk
Ticagrelor
9,333
8,942
8,827
8,763
8,673
8,543
8,397
7,028
6,480
4,822
Clopidogrel 9,291
8,875
8,763
8,688
8,688
8,437
8,286
6,945
6,379
4,751
*Excludes patients with any primary event during the first 30 days
Wallentin L et al. N Engl J Med 2009;361:1045-57.
Primary efficacy endpoint and TIMI Major
Bleeding Through 30 months
(Overall Population)
PEGASUS TIMI 54
Pacientes con IM en los 1-3 años y
con al menos un factor de riesgo aterotrombótico
(n=21,000)
Ticagrelor 60 mg BID
+ 75–150 mg ASA
Ticagrelor 90 mg BID
+ 75–150 mg ASA
Placebo
+ 75–150 mg ASA
Mínimo de 12 meses de seguimiento
Objetivo de Eficacia primaria: Muerte CV, IM o Ictus
Objetivo Primario de Seguridad: Sangrado mayor TIMI
CONCLUSIONES



Los nuevos antiagregantes nos dan
la opción de adaptar el tipo de
tratamiento al tipo de paciente
A diferencia de clopidogrel, ambos,
aunque sobre todo ticagrelor,
mantienen e incluso incrementan
la eficacia en el seguimiento.
La seguridad no parece verse
comprometida
La importancia del tratamiento
“a medida”
HUELVA