Transcript N Engl J Med

Si tengo que elegir,
¿quién se beneficiaría más de
los nuevos antiagregantes?
TRITON-TIMI 38: Primary end point (CV death,
non-fatal MI or non-fatal stroke) and safety all ACS
15
Clopidogrel
Prasugrel
12.1
(781)
End Point (%)
CV Death, NF MI or NF Stroke
9.9
(643)
10
p<0.001
↓ 138 events
↑ 35 events
p=0.03
5
Non-CABG
TIMI Major Bleeding
2.4
(146)
1.8
(111)
0
0
30
60
90 120
180
270
Days After Randomization
Cumulative Kaplan-Meier estimates of the rates of key study end points during the follow-up period
Wiviott SD et al. N Eng J Med 2007;357:2001–2015
360
450
PLATO: Primary end point (CV death, MI or stroke)
at 12 months
15
End Point (%)
11.7
10
9.8
5
Ticagrelor
CV Death, MI or Stroke
p<0.001
Clopidogrel
0
0
2
4
6
Months
Wallentin et al. New Eng J Med 2009;361:1045–1057
8
10
12
PLATO: Safety outcomes (bleeding)
p=0.57
p=0.03
All Major Bleeding
PLATO Definition
All Major Bleeding
TIMI Criteria
Non-CABG-related
Major Bleeding
PLATO Definition
p=0.03
Patients (%)
p=0.43
Wallentin et al. New Eng J Med 2009;361:1045–1057
Non-CABG-related
Major Bleeding
TIMI Criteria
Survival Benefit in PLATO
Hazard ratio
(95 % - confidence limit)
TRITON
All death
Cardiovascular death
PLATO
All death
HR 0,78 (0,69-0,89)
Cardiovascular death
0.5
1
Study drug better
Wiviott SD et al., N Engl J Med 2007; Wallentin L et al., N Engl J Med 2009
1.5
Clopidogrel better
Power to detect reduction in
mortality
Relative risk reduction 20%, α = 0.05
TRITON PLATO
Mortality of control group
2.4 %
5.1 %
Number of patients per study group
6,800
9,333
Power
35%
91%
Wiviott SD et al., N Engl J Med 2007; Wallentin L et al., N Engl J Med 2009
Prasugrel
Ticagrelor
TRITON vs PLATO:
Major Efficacy End Points
Hazard Ratio
Primary Endpoint
CV Death
Nonfatal MI
Nonfatal stroke
All Cause Death
Stent Thrombosis
0.4
0.5
0.6
0.7
0.8
0.9
Prasugrel/Ticagrelor Better
Wiviott SD et al., N Engl J Med 2007; Wallentin L et al., N Engl J Med 2009
1.0
HR
1.1
1.2
1.3
1.4
Clopidogrel Better
1.5
TRITON TIMI-38: Stent Thrombosis
ARC Definite + Probable
3
Any Stent at Index PCI
n=12,844
End Point (%)
Clopidogrel
2.4
(142)
2
74 events
1.1
(68)
1
Prasugrel
HR 0.48
P<0.0001
NNT=77
0
0 30 60 90
180
270
Days
360
ARC = Academic Research Consortium; PCI = percutaneous coronary intervention
Wiviott SD et al. N Engl J Med. 2007;357:2001-2015.
450
Benefit of prasugrel in STEMI
15
Endpoint (%)
CV death / MI / stroke
10
9.5%
5
Prasugrel
TIMI major
non-CABG bleeds
0 30 60 90
Montalescot G et al., Lancet 2009
12.4%
10.0%
6.5%
0
Clopidogrel
180
270
Days
Prasugrel 2.4%
2.1%
Clopidogrel
360
450
Benefit of prasugrel in diabetics
18
16
14
Clopidogrel
CV death / MI / stroke
12.2%
Endpoint (%)
12
10
Prasugrel
8
6
4
2
0
17.0%
TIMI major
non-CABG bleeds
Clopidogrel
Prasugrel
0 30 60 90
180
Days
Wiviott SD et al. Circulation 2008; 118: 1626-1636
270
360
HR 0.70
P < 0.001
NNT = 21
2.6%
2.5%
450
European NSTE ACS Summit
PLATO
September 18th / 19th 2013
Brussels
PLATO
Diabetes N=4662
Primary endpoint
CV death, MI or stroke (%)
20
Diabetes
15
10
No diabetes
5
0
0
Number at risk
Diabetes
Ticagrelor
Clopidogrel
No diabetes
Ticagrelor
Clopidogrel
60
120
180
240
300
360
Days after randomization
6999
6952
6507
6434
6407
6318
6252
6153
5143
5044
3955
3869
3191
3097
2326
2336
2113
2084
2045
2041
1959
1968
1593
1604
1199
1225
953
975
European NSTE ACS Summit
September 18th / 19th 2013
Brussels
TRITON-TIMI 38
% eventos isquémicos (muerte CV, infarto, ictus)
prasugrel
PLATO
clopidogrel
ticagrelor
clopidogrel
HR=0,81
HR=0,86
HR=0,70
HR=0,84
HR=0,83
HR=0,88
(0,73-0,90)
(0,76-0,98)
(0,58-0,85)
(0,77-0,92)
(0,74-0,93)
(0,76-1,03)
Todos
No diabetes
Diabetes
Todos
No diabetes
Diabetes
(n=13.608)
(n=10.462)
(n=3.146)
(n=18.624)
(n=13.951)
(n=4.662)
Fernandez-Ortiz A, Vivas D, García-Rubira JC. Rev Esp Cardiol Supl. 2010;10:42D-48D
Ticagrelor vs clopidogrel in ACS in relation to renal function
European NSTE ACS Summit
September 18th / 19th 2013
Brussels
22,0%
Ccr <60mL/min (n=3.237)
17,3%
HR 0,77 (0,65-0,90)
8,9%
7,9%
HR 0,90 (0,79-1,02)
Ccr ≥60mL/min (n=11.965)
James S, et al. Circulation 2010;122(11):1056-67.
Nuevos antiagregantes ¿a quién?: preguntas
 ¿quién es el mejor candidato para prasugrel?
 ¿quién es el mejor candidato para ticagrelor?
 ¿quién es el mejor candidato para clopidogrel?
 ¿puedo cambiar el tratamiento? ¿cómo?
 ¿nuevos en la fase aguda mejor, luego clopi?
 Si solo puedo disponer de uno, ¿cuál?