CẬP NHẬT điều TRỊ KHÁNG TIỂU cầu kép sau khi đặt stent

Antiplatelet Therapy to Support Primary PCI for STEMI Reperfusion at a PCI-Capable Hospital 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction... I IIa I

T S N g u y ễ n C ử u L ợ i - T r u n g t â m T i m m ạ c h - B ệ n h v i ệ n T r u n g

Ư ơ n g H u ế

CẬP NHẬT ĐIỀU TRỊ KHÁNG TIỂU CẦU KÉP SAU KHI ĐẶT STENT

TỈ lệ tử vong sau ACS tăng DẦN TRONG 6 THÁNG ĐẦU

SAU ĐẶT STENT

Tỷ lệ tử vong sau xuất viện 16 -180 ngày (NC sổ bộ GRACE) *

Fox KA, et al Eur Heart J 2010;31:2755−2764; Vatspace Available at

http://vatspace.com/issue-4/the-unmeet-need-in-acute-coronary-syndrome/ (accessed November 2013)

Ngày từ khi nhập viện

ST không chênh lên

ST chênh lên

Không xác định

Post-discharge deaths occurred in 68%, 86% and 97% of STEMI, NSTEMI and UA patients, respectively

ACS, acute coronary syndromes; GRACE, Global Registry of Acute Coronary Events; MI, myocardial infarction; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; UA, unstable angina

Fox KA, et al Eur Heart J 2010;31:2755–2764

Nghiên cứu sổ bộ GRACE (Anh, Bỉ) trên BN HCVC

1/5 BN ACS tử vong trong vòng 5 năm

1/8 BN STEMI tử vong trong 3 năm

• Prospective study of 3-year outcomes in a consecutive series of STEMI patients (n=6820)

STEMI, ST-segment elevation myocardial infarction

Nauta ST, et al PLoS One 2011;6:e26917

1/8 BN NSTEMI tử vong trong 3 năm

• Prospective study of 3-year outcomes in a consecutive series of NSTEMI patients (n=7614)

NSTEMI, non-ST-segment elevation myocardial infarction

Nauta ST, et al PLoS One 2011;6:e26917

Time from event (years)

2012 ACCF/ AHA Guidelines:

antiplatelet therapy for Management of UA/NSTEMI

2012 ESC Guidelines:

antiplatelet therapy for STEMI PTS undergoing PCI

DƯỢC ĐỘNG HỌC của các thuốc ức chế P2Y12

Figure adapted from Schömig A (2009) CYP, cytochrome P450

Schömig A N Engl J Med 2009;361:1108–1111

Thủy phân bởi esterase

Oxi hóa phụ thuộcCYP CYP1A2 CYP2B6 CYP2C19

Oxi hóa phụ thuộcCYP CYP2C19 CYP3A4/5 CYP2B6

Chất có hoạt tính Chất chuyển hóa trung gian Tiền thuốc

180-mg loading dose

BRILIQUE (n=9,333)

*STEMI patients scheduled for primary PCI were randomised; however, they may not have received PCI.

† A loading dose of 300-mg clopidogrel was permitted in patients not previously treated with clopidogrel, with an additional 300 mg allowed at the discretion of the investigator.

‡ The PLATO study expanded the definition of major bleeding to be more inclusive compared with previous studies in ACS patients The primary safety endpoint was the first occurrence of any major bleeding event.

90 mg bid + ASA maintenance dose

300-mg loading dose† 75 mg qd + ASA maintenance dose

Clopidogrel (n=9,291)

Primary efficacy endpoint:

Composite of CV death, MI (excluding silent MI), or stroke

Primary safety endpoint:

Total PLATO major bleeding‡

Visit 2 Visit 3 Visit 4 Visit 5 Visit 6

Initial Treatment approaches

• Medically managed (n=5,216 — 28.0%)

• Invasively managed (n=13,408 — 72.0%)

Wallentin L, et al N Engl J Med 2009;361:1045–1057

James S, et al Am Heart J 2009;157:599–605

Randomisation

• All patients were hospitalised with symptom onset <24 hours

• Patients could be taking clopidogrel at time of randomisation

PLATO: Study Design

Ticagrelor

Huyết khối trong stent

Ticagrelor (n=5,640)

Clopidogrel (n=5,649)

HR

Huyết khối trong stent, %

0.009 0.02 0.01 (đánh giá trên tất cả các loại stent trong nghiên cứu)

*Time-at-risk is calculated from first stent insertion in the study or date of randomisation

**Nominal p value

Wallentin L, et al N Engl J Med 2009;361:1045–1057

Both groups included aspirin

*NNT at one year

PLATO: Primary Efficacy Endpoint

(Composite of CV Death, MI, or Stroke)

Wallentin L, et al N Engl J Med 2009;361:1045–1057

All values presented by PLATO criteria

Both groups included aspirin

Non-CABG-Major Bleeding

Major and Minor Bleeding

Kết quả Holter

và biến cố liên quan tới ngưng xoang

Holter tuần đầu

Ticagrelor (n=1,451)

Clopidogrel (n=1,415) p Ngưng xoang ≥3s, %

Ngưng xoang ≥5s, %

5.8 2.0

3.6 1.2

0.01

0.10

Holter sau 30 ngày

Ticagrelor (n= 985)

Clopidogrel (n=1,006) p Ngưng xoang ≥3s, %

Ngưng xoang ≥5s, %

2.1 0.8

1.7 0.6

0.52 0.60

PLATO: Bradycardia-related Events

All Patients

BRILIQUE (n=9,235)

Clopidogrel (n=9,186) P Value

• Ventricular pauses ≥3 seconds occurred in 5.8% of BRILIQUE-treated patients vs 3.6% of

clopidogrel-treated patients in the acute phase, and 2.1% and 1.7% after

Wallentin L, et al N Engl J Med 2009;361:1045–1057

BRILIQUE: Summary of Product Characteristics, 2010

PLATO: Dyspnoea

• BRILIQUE-associated dyspnoea was mostly mild to moderate in severity and did not reduce efficacy

• Most events were reported as single episode occurring early after starting treatment

• Not associated with new or worsening heart or lung disease

• In 2.2% of patients, investigators considered dyspnoea causally related to treatment with BRILIQUE

• Label precautions and warnings: use with caution in patients with history of asthma and COPD

BRILIQUE: Summary of Product Characteristics, 2010

Wallentin L, et al N Engl J Med 2009;361:1045–1057

Storey R, et al J Am Coll Cardio 2010;55(Suppl 1):A108.E1007

Dyspnoea in the PLATO trial BRILIQUE Clopidogrel P Value

Incidence of dyspnoea adverse events (%) 13.8 7.8 <0.001 Patients who discontinued treatment due to

dyspnoea (%) 0.9 0.1 <0.001

Wallentin L, et al N Engl J Med 2009;361:1045–1057

Hiệu quả Ticagrelor đồng nhất trên các phân nhóm bất kể

kiểu gen CYP2C19

* Biến cố gộp: tử vong tim mạch, NMCT, đột quỵ

Ngày từ khi nhập viện

Clopidogrel: biến đổi kiểu gen CYP2C19 Clopidogrel: không biến đổi kiểu gen CYP2C19

BRILINTA: không biến đổi kiểu gen CYP2C19

BRILINTA: biến đổi kiểu gen CYP2C19

PLATO: So sánh PRU bằng xét nghiệm VerifyNow

giữa Clopidogrel (C) và Ticagrelor (T)

0 100 200 300 400 500

235 PRU

Antiplatelet Therapy to Support

Primary PCI for STEMI

Reperfusion at a PCI-Capable Hospital

2013 ACCF/AHA Guideline for the Management of ST-Elevation

Myocardial Infarction

I IIa IIb III

ANTIPLATELET THERAPY TO SUPPORT

PRIMARY PCI FOR STEMI

Aspirin 162 to 325 mg should be given before primary PCI

After PCI, aspirin should be continued indefinitely

I IIa IIb III

early as possible or at time of primary PCI to patients with STEMI Options include:

• Clopidogrel 600 mg; or

• Prasugrel 60 mg; or

• Ticagrelor 180 mg

ANTIPLATELET THERAPY TO SUPPORT PRIMARY PCI FOR STEMI

STEMI who receive a stent (BMS or DES) during primary PCI using the following maintenance doses:

• Clopidogrel 75 mg daily; or

I IIa IIb III

• Prasugrel 10 mg daily; or

• Ticagrelor 90 mg twice a day*

*The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily

ANTIPLATELET THERAPY TO SUPPORT

PRIMARY PCI FOR STEMI

It is reasonable to use 81 mg of aspirin per day in preference to higher maintenance doses after primary PCI

I IIa IIb III

I IIa IIb III

prior stroke or transient ischemic attack

ADJUNCTIVE ANTITHROMBOTIC THERAPY TO SUPPORT

REPERFUSION WITH FIBRINOLYTIC THERAPY

ANTIPLATELET THERAPY TO SUPPORT PCI AFTER FIBRINOLYTIC THERAPY

After PCI, aspirin should be continued indefinitely

b A 600-mg loading dose should be given before or at the time

of PCI to patients who did not receive a previous loading dose and who are undergoing PCI more than 24 hours after

receiving fibrinolytic therapy; and

I IIa IIb III

I IIa IIb III

Clopidogrel should be provided as follows:

a A 300-mg loading dose should be given before or at the time

of PCI to patients who did not receive a previous loading dose and who are undergoing PCI within 24 hours of receiving fibrinolytic therapy;

c A dose of 75 mg daily should be given after PCI

ANTIPLATELET THERAPY TO SUPPORT PCI AFTER FIBRINOLYTIC THERAPY

After PCI, it is reasonable to use 81 mg of aspirin per day in preference to higher maintenance doses

Prasugrel, in a 60-mg loading dose, is reasonable once the coronary anatomy is known in patients who did not receive a previous loading dose of clopidogrel at the time of administration

of a fibrinolytic agent, but prasugrel should not be given sooner than 24 hours after administration of a fibrin-specific agent or 48 hours after administration of a non–fibrin-specific agent

I IIa IIb III

I IIa IIb III

Prasugrel, in a 10-mg daily maintenance dose, is reasonable after PCI

I IIa IIb III

I IIa IIb III

prior stroke or transient ischemic attack

Antiplatelet therapy

ASA is recommended for all patients without contraindication at

an initial oral loading dose 0f 150-300mg (or 80-150mg IV) and a

maintenance dose of 75-100mg daily lonterm regardless of

treatment strategy

A P2Y12 inhibitor is recommended in addition to ASA and

maintained over 12 months unless there are contraindications

such as excessive bleeding risk Options are:

* Clopidogrel (600mg loading dose, 75mg daily dose) only

when Prasugrel and Ticagrelor are not available or are

contraindicated

THANKS FOR YOUR ATTENTION