¿Cuáles son las limitaciones de los
nuevos antiagregantes?
TIMI Major Bleeding TIMI Major Bleeding TRITON-TIMI 38 versus PLATOTRITON-TIMI 38 versus PLATO
Clopidogrel
Prasugrel
Wiviott SD et al., N Engl J Med 2007; Wallentin L et al., N Engl J Med 2009
P = 0.03
1.81.8
2.42.4
TRITON PLATO
Ticagrelor2.22.2
2.82.8
P = 0.03
0
1
3
2
Rate of non CABG bleeds (%)Rate of non CABG bleeds (%)
0.5 1 2
OVERALL
Prasugrel Better Clopidogrel Better
No
YesPrior Stroke / TIA Pint = 0.006
<75
≥75Age
Pint = 0.18
≥60 kg
<60 kgWeight
Pint = 0.36
www.timi.org – Accessed on July 16, 2008
Contraindication with history of cerebro-vascular event
Hazard Ratio for net clinical outcome
TRITON-TIMI 38TRITON-TIMI 38
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17086 11.5 10.9 1.06 (0.96, 1.16)<80 kg
1296 12.6 15.2 0.82 (0.60, 1.12)≥60 kg
5237 10.7 10.5 1.01 (0.85, 1.21)
<60 kg
13184 11.9 11.4 1.05 (0.94, 1.16)Female
2846 14.2 13.3 1.04 (0.84, 1.29)
Male
15574 11.1 10.8 1.04 (0.94, 1.15)≥75 Years
7892 14.4 13.6 1.07 (0.95, 1.22)<75 Years
10528 9.5 9.5 1.00 (0.87, 1.13)<65 Years
1136 14.6 14.9 0.99 (0.71, 1.37)Age Group
17284 11.4 11.0 1.04 (0.95, 1.14)No
1092 7.3 7.8 0.94 (0.60, 1.49)Previous TIA/Non-hemorrhagic Stroke
17329 11.8 11.4 1.04 (0.95, 1.14)No
Yes
Central/South America
≥80 kg
North America
1230 15.6 13.2 1.22 (0.89, 1.66)Europe/Middle East/Africa
1692 10.6 10.8 1.03 (0.76, 1.40)Asia/Australia
4621 14.1 14.8 0.95 (0.81, 1.12)Region
13800 10.8 10.0 1.08 (0.97, 1.20)No
9423 11.4 10.5 1.08 (0.95, 1.23)Medical History of DM
8959 11.7 11.9 0.99 (0.88, 1.13)
0.2
P value(Interaction)
0.68
0.77
0.42
1.00
0.76
0.12
0.35
0.75
1752 12.9 12.2 1.06 (0.80, 1.40)13747 11.1 11.0 1.01 (0.91, 1.13)
0.21
HRs and cumulative incidence of major bleeding (pre-defined subgroups - cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.15
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17086 11.5 10.9 1.06 (0.96, 1.16)<80 kg
1296 12.6 15.2 0.82 (0.60, 1.12)≥60 kg
5237 10.7 10.5 1.01 (0.85, 1.21)
<60 kg
13184 11.9 11.4 1.05 (0.94, 1.16)Female
2846 14.2 13.3 1.04 (0.84, 1.29)
Male
15574 11.1 10.8 1.04 (0.94, 1.15)≥75 Years
7892 14.4 13.6 1.07 (0.95, 1.22)<75 Years
10528 9.5 9.5 1.00 (0.87, 1.13)<65 Years
1136 14.6 14.9 0.99 (0.71, 1.37)Age Group
17284 11.4 11.0 1.04 (0.95, 1.14)No
1092 7.3 7.8 0.94 (0.60, 1.49)Previous TIA/Non-hemorrhagic Stroke
17329 11.8 11.4 1.04 (0.95, 1.14)No
Yes
Central/South America
≥80 kg
North America
1230 15.6 13.2 1.22 (0.89, 1.66)Europe/Middle East/Africa
1692 10.6 10.8 1.03 (0.76, 1.40)Asia/Australia
4621 14.1 14.8 0.95 (0.81, 1.12)Region
13800 10.8 10.0 1.08 (0.97, 1.20)No
9423 11.4 10.5 1.08 (0.95, 1.23)Medical History of DM
8959 11.7 11.9 0.99 (0.88, 1.13)
0.2
P value(Interaction)
0.68
0.77
0.42
1.00
0.76
0.12
0.35
0.75
1752 12.9 12.2 1.06 (0.80, 1.40)13747 11.1 11.0 1.01 (0.91, 1.13)
0.21
HRs and cumulative incidence of major bleeding (pre-defined subgroups - cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.15
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17086 11.5 10.9 1.06 (0.96, 1.16)<80 kg
1296 12.6 15.2 0.82 (0.60, 1.12)≥60 kg
5237 10.7 10.5 1.01 (0.85, 1.21)
<60 kg
13184 11.9 11.4 1.05 (0.94, 1.16)Female
2846 14.2 13.3 1.04 (0.84, 1.29)
Male
15574 11.1 10.8 1.04 (0.94, 1.15)≥75 Years
7892 14.4 13.6 1.07 (0.95, 1.22)<75 Years
10528 9.5 9.5 1.00 (0.87, 1.13)<65 Years
1136 14.6 14.9 0.99 (0.71, 1.37)Age Group
17284 11.4 11.0 1.04 (0.95, 1.14)No
1092 7.3 7.8 0.94 (0.60, 1.49)Previous TIA/Non-hemorrhagic Stroke
17329 11.8 11.4 1.04 (0.95, 1.14)No
Yes
Central/South America
≥80 kg
North America
1230 15.6 13.2 1.22 (0.89, 1.66)Europe/Middle East/Africa
1692 10.6 10.8 1.03 (0.76, 1.40)Asia/Australia
4621 14.1 14.8 0.95 (0.81, 1.12)Region
13800 10.8 10.0 1.08 (0.97, 1.20)No
9423 11.4 10.5 1.08 (0.95, 1.23)Medical History of DM
8959 11.7 11.9 0.99 (0.88, 1.13)
0.2
P value(Interaction)
0.68
0.77
0.42
1.00
0.76
0.12
0.35
0.75
1752 12.9 12.2 1.06 (0.80, 1.40)13747 11.1 11.0 1.01 (0.91, 1.13)
0.21
HRs and cumulative incidence of major bleeding (pre-defined subgroups - cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.15
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17086 11.5 10.9 1.06 (0.96, 1.16)<80 kg
1296 12.6 15.2 0.82 (0.60, 1.12)≥60 kg
5237 10.7 10.5 1.01 (0.85, 1.21)
<60 kg
13184 11.9 11.4 1.05 (0.94, 1.16)Female
2846 14.2 13.3 1.04 (0.84, 1.29)
Male
15574 11.1 10.8 1.04 (0.94, 1.15)≥75 Years
7892 14.4 13.6 1.07 (0.95, 1.22)<75 Years
10528 9.5 9.5 1.00 (0.87, 1.13)<65 Years
1136 14.6 14.9 0.99 (0.71, 1.37)Age Group
17284 11.4 11.0 1.04 (0.95, 1.14)No
1092 7.3 7.8 0.94 (0.60, 1.49)Previous TIA/Non-hemorrhagic Stroke
17329 11.8 11.4 1.04 (0.95, 1.14)No
Yes
Central/South America
≥80 kg
North America
1230 15.6 13.2 1.22 (0.89, 1.66)Europe/Middle East/Africa
1692 10.6 10.8 1.03 (0.76, 1.40)Asia/Australia
4621 14.1 14.8 0.95 (0.81, 1.12)Region
13800 10.8 10.0 1.08 (0.97, 1.20)No
9423 11.4 10.5 1.08 (0.95, 1.23)Medical History of DM
8959 11.7 11.9 0.99 (0.88, 1.13)
0.2
P value(Interaction)
0.68
0.77
0.42
1.00
0.76
0.12
0.35
0.75
1752 12.9 12.2 1.06 (0.80, 1.40)13747 11.1 11.0 1.01 (0.91, 1.13)
0.21
HRs and cumulative incidence of major bleeding (pre-defined subgroups - cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.15
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17086 11.5 10.9 1.06 (0.96, 1.16)<80 kg
1296 12.6 15.2 0.82 (0.60, 1.12)≥60 kg
5237 10.7 10.5 1.01 (0.85, 1.21)
<60 kg
13184 11.9 11.4 1.05 (0.94, 1.16)Female
2846 14.2 13.3 1.04 (0.84, 1.29)
Male
15574 11.1 10.8 1.04 (0.94, 1.15)≥75 Years
7892 14.4 13.6 1.07 (0.95, 1.22)<75 Years
10528 9.5 9.5 1.00 (0.87, 1.13)<65 Years
1136 14.6 14.9 0.99 (0.71, 1.37)Age Group
17284 11.4 11.0 1.04 (0.95, 1.14)No
1092 7.3 7.8 0.94 (0.60, 1.49)Previous TIA/Non-hemorrhagic Stroke
17329 11.8 11.4 1.04 (0.95, 1.14)No
Yes
Central/South America
≥80 kg
North America
1230 15.6 13.2 1.22 (0.89, 1.66)Europe/Middle East/Africa
1692 10.6 10.8 1.03 (0.76, 1.40)Asia/Australia
4621 14.1 14.8 0.95 (0.81, 1.12)Region
13800 10.8 10.0 1.08 (0.97, 1.20)No
9423 11.4 10.5 1.08 (0.95, 1.23)Medical History of DM
8959 11.7 11.9 0.99 (0.88, 1.13)
0.2
P value(Interaction)
0.68
0.77
0.42
1.00
0.76
0.12
0.35
0.75
1752 12.9 12.2 1.06 (0.80, 1.40)13747 11.1 11.0 1.01 (0.91, 1.13)
0.21
HRs and cumulative incidence of major bleeding (pre-defined subgroups - cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.15
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17086 11.5 10.9 1.06 (0.96, 1.16)<80 kg
1296 12.6 15.2 0.82 (0.60, 1.12)≥60 kg
5237 10.7 10.5 1.01 (0.85, 1.21)
<60 kg
13184 11.9 11.4 1.05 (0.94, 1.16)Female
2846 14.2 13.3 1.04 (0.84, 1.29)
Male
15574 11.1 10.8 1.04 (0.94, 1.15)≥75 Years
7892 14.4 13.6 1.07 (0.95, 1.22)<75 Years
10528 9.5 9.5 1.00 (0.87, 1.13)<65 Years
1136 14.6 14.9 0.99 (0.71, 1.37)Age Group
17284 11.4 11.0 1.04 (0.95, 1.14)No
1092 7.3 7.8 0.94 (0.60, 1.49)Previous TIA/Non-hemorrhagic Stroke
17329 11.8 11.4 1.04 (0.95, 1.14)No
Yes
Central/South America
≥80 kg
North America
1230 15.6 13.2 1.22 (0.89, 1.66)Europe/Middle East/Africa
1692 10.6 10.8 1.03 (0.76, 1.40)Asia/Australia
4621 14.1 14.8 0.95 (0.81, 1.12)Region
13800 10.8 10.0 1.08 (0.97, 1.20)No
9423 11.4 10.5 1.08 (0.95, 1.23)Medical History of DM
8959 11.7 11.9 0.99 (0.88, 1.13)
0.2
P value(Interaction)
0.68
0.77
0.42
1.00
0.76
0.12
0.35
0.75
1752 12.9 12.2 1.06 (0.80, 1.40)13747 11.1 11.0 1.01 (0.91, 1.13)
0.21
HRs and cumulative incidence of major bleeding (pre-defined subgroups - cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.15
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
Ticagrelor better Clopidogrel better
Ti. Cl.Total
Patients
KM % atMonth 12
HR (95% CI)Hazard Ratio
(95% CI)
Yes
Yes
Revascularization History of CABG
Sex
Weight Group
≥65 Years
Characteristic
0.5 1.0 2.0
17256 9.5 11.2 0.86 (0.78, 0.94)<80 kg
1312 13.1 17.3 0.75 (0.60, 0.99)≥60 kg
5288 11.2 13.2 0.83 (0.71, 0.97)
<60 kg
13336 9.2 11.1 0.85 (0.76, 0.95)Female
2878 16.8 18.3 0.94 (0.78, 1.12)
Male
15744 8.6 10.4 0.82 (0.74, 0.91)≥75 Years
7979 13.2 16.0 0.83 (0.74, 0.94)<75 Years
10643 7.2 8.5 0.85 (0.74, 0.97)<65 Years
1152 19.0 20.8 0.87 (0.66, 1.13)Age Group
17462 9.2 11.1 0.84 (0.76, 0.93)No
1106 19.5 21.7 0.88 (0.67, 1.15)Previous TIA/Non-hemorrhagic Stroke
17518 9.2 11.0 0.84 (0.77, 0.93)No
Yes
Central/South America
≥80 kg
North America
1237 15.2 17.9 0.86 (0.65, 1.13)Europe/Middle East/Africa
1714 11.4 14.8 0.80 (0.61, 1.04)Asia/Australia
4662 14.1 16.2 0.88 (0.76, 1.03)Region
13962 8.4 10.2 0.83 (0.74, 0.92)No
9513 8.3 10.5 0.79 (0.69, 0.90)Medical History of DM
9055 11.4 12.8 0.90 (0.79, 1.01)
0.2
p- value(Interaction)
0.76
0.84
0.86
0.22
0.82
0.36
0.17
0.05
1814 11.9 9.6 1.25 (0.93, 1.67)13859 8.8 11.0 0.80 (0.72, 0.90)
0.49
Primary Endpoint in Pre-defined Subgroups (Cont’d)
Wallentin L, et al.New Engl J Med. 2009;361.
14
1° efficacy endpoint1° efficacy endpoint 1° safety endpoint1° safety endpoint
Previous non-hemorh. CVANoYes
Age Group< 75 years> 75 years
Weight group< 60 kg> 60 kg
Previous non-hemorh. CVANoYes
Age Group< 75 years> 75 years
Weight group< 60 kg> 60 kg
ticagrelor betterticagrelor betterclopidogrel betterclopidogrel better ticagrelor betterticagrelor betterclopidogrel betterclopidogrel better
No contraindication for ticagrelor with previous stroke
Wallentin L et al., N Engl J Med 2009
PLATOPLATO
Estimated Event Rate (CV Death / MI / Stroke) at 1 Y ear
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
25 35 45 55 65 75 85 95
Age (years)
Ev
en
t R
ate
Ticagrelor ClopidogrelOne Model - Interaction
Age and primary efficacy outomes in PLATO
Husted et al 2011, ACC
6
PLATO: total mortality according to PLATO: total mortality according to prior history of stroke/TIAprior history of stroke/TIA
James S, et al. Circulation 2012;125:2914–2921.
%
European NSTE ACS SummitSeptember 18th / 19th 2013 Brussels
European NSTE ACS SummitSeptember 18th / 19th 2013 Brussels
European NSTE ACS SummitSeptember 18th / 19th 2013 Brussels
European NSTE ACS SummitSeptember 18th / 19th 2013 Brussels
¿a quién no debo administrar prasugrel?
¿a quién no de administrar ticagrelor?
¿a quién no debo administrar clopidogrel?
¿Cuánto debo esperar para operar tras suspender el tratamiento?
Nuevos antiagregantes ¿a quién?: preguntas