Kháng tiểu cầu trong bệnh động mạch vành nguy cơ xuất huyết trên bệnh nhân châu á

KHÁNG TIỂU CẦU TRONG BỆNH MV VÀ NGUY
CƠ XH TRÊN BN CHÂU Á
TS.BS ĐỖ QUANG HUÂN, FACC, FSCAI

24/10/2009

TS. BS.DO QUANG HUAN



24/10/2009

TS. BS.DO QUANG HUAN


24/10/2009

TS. BS.DO QUANG HUAN


24/10/2009

TS. BS.DO QUANG HUAN


19/06/2009

TS.BS DO QUANG HUAN


24/10/2009

24/10/2009

TS. BS.DO QUANG HUAN


2013 ACCF/AHA Guideline for the
Management of ST-Elevation Myocardial
Infarction
Developed in Collaboration with American College of Emergency Physicians and
Society for Cardiovascular Angiography and Interventions
© American College of Cardiology Foundation and American Heart Association, Inc.

24/04/2016

TS. BS.DO QUANG HUAN, FACC, FSCAI


Antiplatelet Therapy to Support
Primary PCI for STEMI
I IIa IIb III

Aspirin 162 to 325 mg should be given before
primary PCI.
I IIa IIb III

After PCI, aspirin should be continued indefinitely.

24/04/2016

TS. BS.DO QUANG HUAN, FACC, FSCAI


2014 AHA/ACC Guideline for the
Management of Patients With Non–STElevation Acute Coronary Syndromes
Developed in Collaboration with the Society of Thoracic Surgeons and Society for
Cardiovascular Angiography and Interventions
Endorsed by the American Association for Clinical Chemistry
© American College of Cardiology Foundation and American Heart Association

24/04/2016

TS. BS.DO QUANG HUAN, FACC, FSCAI


Treated With an Initial Invasive or Ischemia-Guided Strategy
Recommendations
Non–enteric-coated, chewable aspirin (162 mg to 325 mg)
should be given to all patients with NSTE-ACS without
contraindications as soon as possible after presentation,
and a maintenance dose of aspirin (81 mg/d to 162 mg/d)
should be continued indefinitely.
In patients with NSTE-ACS who are unable to take aspirin
because of hypersensitivity or major gastrointestinal
intolerance, a loading dose of clopidogrel followed by a
daily maintenance dose should be administered.

24/04/2016

TS. BS.DO QUANG HUAN, FACC, FSCAI

COR

LOE

I

A

I

B


CURE: Benefit of Clopidogrel
Irrespective of Revascularization Status
n = 12562

PCI Group

Medical Rx Group
0.20

10%

0.15

Placebo

8,1%

0.10

Clopidogrel

0.05

CVD/MI/stroke

CVD/MI/stroke

0.20

n=2658

13,2%

Placebo

0.15

9,6%

0.10

Clopidogrel

0.05

RR: 0.72 (0.57-0.90)

RR: 0.80 (0.69-0.92)
0.0

0.0

4

100

200

300

4

CABG Group

0.15

200

300

n=2027

16,2%

Placebo

0.20

CVD/MI/stroke

100

Clopidogrel

14,5%

0.10
0.05

RR: 0.89 (0.71-1.11)
0.0

4

24/04/2016
Fox et al. Circulation 2004;110:1202-8.

100

200

300

TS. BS.DO QUANG HUAN, FACC, FSCAI
ESC 2008 satellite symposium- with permission of Pr. Mehta

24/04/2016

TS. BS.DO QUANG HUAN, FACC, FSCAI


CURRENT-OASIS 7 Trial
A Randomized, Double-Blind, 2x2 Factorial Trial of Clopidogrel High
vs. Standard Loading Dose and High versus Low Dose ASA in ACS
or STEMI Managed with an Early Invasive Strategy
25,087 ACS or STEMI Patients
Angiography with intended PCI <24 hrs
No restriction on use of GP IIb/IIIa inhibitors

Randomized
HIGH DOSE
Clopidogrel 600 mg
then 150 mg OD x
7d then 75 mg OD
Low Dose
ASA
(≤100 mg)

Primary Efficacy Outcome
CV Death / MI / stroke at 30 days
Safety Outcome
30-day bleeding complications

High Dose

ASA
(≥300 mg)

24/10/2009
Mehta SR et al. Am Heart J 2008; in press

STANDARD DOSE
Clopidogrel 300 mg
followed by 75 mg
daily
Low Dose
ASA
(≤100 mg)

High Dose
ASA
(≥300 mg)

TS. BS.DO QUANG HUAN
ESC 2008 satellite symposium- with permission of Pr. Mehta


Clopidogrel: Double vs Standard Dose
Primary Outcome: PCI Patients
CV Death, MI or Stroke
Clopidogrel Standard

0.02

0.03

Clopidogrel Double

0.01

HR 0.85
95% CI 0.74-0.99
P=0.036

0.0

Cumulative Hazard

0.04

15% RRR

0
24/10/2009

3

6

9

12

15

18

21

TS. BS.DO QUANG HUAN

Days

24

27

30


Clopidogrel: Double vs Standard Dose
Definite Stent Thrombosis (Angio confirmed

0.008

42%
RRR

0.004

Clopidogrel Double Dose

HR 0.58
95% CI 0.42-0.79
P=0.001

0.0

Cumulative Hazard

0.012

Clopidogrel Standard Dose

0
24/10/2009

3

6

9

12

15

Days

18

TS. BS.DO QUANG HUAN

21

24

27

30


10/18/2016

TS. BS.DO QUANG HUAN


Thienopyridines: Formation of Active Metabolite
O

C

O

CH3

O

N

S

O

Cl

Clopidogrel

CYPs:

85% Inactive
Metabolites

1A2

2B6
O

S

S

F

Prasugrel
O
O

CYPs:

O CH3

C

N

S

F

Cl

CYPs:

2B6

3A

2C9

2C9
O

OCH3

Oxidation
(Cytochrome P450)

3A

N

2C19

Active
HOOC

HS
Metabolite
10/18/2016

Hydrolysis
(Esterases)

N

O

2C19

Oxidation
(Cytochrome P450)

O

C
C H3

2C19
O

2B6

HOOC
HS

N

Cl

TS. BS.DO QUANG HUAN

N
F

Active
Metabolite


TITAN

TRITON-TIMI 38
ASA

n= 13,608

2o endpoints: CV death, MI, Stroke, Rehosp-Rec Isch, CV death, MI,
UTVR
Stent Thrombosis (ARC definite/prob.)
Safety
bleeds,
Life-threatening
bleeds
10/18/2016endpoints: TIMI major
TS. BS.DO
QUANG
HUAN

Wiviott et al., NEJM 2007; 357: 2001-5


TITAN

TRITON-TIMI 38
15

Endpoint (%)

1o EP: CV Death / MI /
Stroke

Clopidogrel

10

12.1 HR 0.81
(0.73-0.90)
P=0.0004
9.9

Prasugrel

5

0

0
10/18/2016

90

180

Days

270

TS. BS.DO QUANG HUAN

360

450
Wiviott et al., NEJM 2007; 357: 2001-5


24/10/2009

TS. BS.DO QUANG HUAN


24/10/2009

TS. BS.DO QUANG HUAN


24/10/2009

TS. BS.DO QUANG HUAN

24/10/2009

TS. BS.DO QUANG HUAN