¿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