Nhóm thuốc mới ức chế p2y12 không hơn gì clopidogrel với nhiều bệnh nhân tim mạch

New P2Y12 Blockers are NOT Superior to Clopidogrel for some groups of cardiovascular patients Peter M... Prasugrel - TRITON – TIMI 38 Prasugrel vs Clopidogrel in High-risk ACS Prasugre

New P2Y12 Blockers are NOT

Superior to Clopidogrel for some

groups of cardiovascular patients

Peter M Pollak MD

New P2Y12 Drugs

©2011 MFMER | 3138928-3

Ticagrelor

Ticagrelor: PLATO

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

NNT = 52

Ticagrelor and PLATO trials

Important Exclusions

• Thrombolytics within 24 hours

• Not for pharmacoinvasive strategy

• Any Oral Anticoagulation

 not for Afib/WOEST

• Risk of Bradycardia (trend toward Syncope)

• Use of strong P450 3A inhibitor

 Diltiazem, Verapamil, Antiviral & Antifungal

Harm

• More non CABG major bleeding (NNH=166)

• But safer if CABG

• Dyspnea – 14% (1% stopped drug)

Wallentin L: NEJM 2009; Cannon CP: Lancet 2010

No benefit with high dose Aspirin

Mahaffey K W et al Circulation 2011;124:544-554

Prasugrel - TRITON – TIMI 38 Prasugrel vs Clopidogrel in High-risk ACS

Prasugrel Clopidogrel

Wiviott SD: NEJM 2007

Days From First Dose

CV Death, MI, Stroke,

UR, GPIIb/IIIa Bailout

Pre-treatment 10.8

10.0 Pre-treatment

Hazard Ratio, 0.997 (95% 0.83, 1.20) P=0.98

P=0.81 (95% 0.84, 1.25) Hazard Ratio, 1.02

No Pre-treatment

10.8 9.8

No Pre-treatment

Prasugrel - ACCOAST

• Prasugrel given at ACS diagnosis vs at PCI

• Increase in major and life-threatening bleeding

• Including the non CABG patients

Prasugrel - TRILOGY ACS trial

Primary Efficacy Endpoint (CV Death, MI, Stroke) and

TIMI Major Bleeding Through 30 Months

(Overall TRILOGY population)

Prasugrel Summary

(all with increased bleeding)

Cangrelor – CHAMPION Trials

• Direct platelet P2Y12 receptor antagonist

• Parenteral administration

• T1/2 = 3 to 6 minutes

• Offset = 60 minutes

• 8716 patients undergoing PCI

• Pre-treated with 600mg Clopidogrel

Conclusions - Themes

consistent and stronger antiplatelet effect when

compared with Clopidogrel

effects

Thank you!

Pollak.peter@mayo.edu

ROC Curve Analysis

Relation of 30-day PRU With Primary Efficacy Endpoint

HPR: > 178 Sensitivity: 47%

Specificity: 59%

ACCOAST design

Prasugrel 30 mg

Prasugrel 60 mg Prasugrel 30 mg

Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days

PCI

1 ° Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa bailout, at 7 days

Placebo

Coronary Angiography

n~4100 (event driven)

Coronary Angiography

PCI

CABG

or Medical Management (no prasugrel)

CABG

or

Medical

Management

(no more prasugrel)

Montalescot G et al Am Heart J 2011;161:650-656

Randomize 1:1

Double-blind

NSTEMI + Troponin ≥ 1.5 times ULN local lab value

Clopidogrel naive or on long term clopidogrel 75 mg

ACCOAST- Pharmacodynamic Sub-Study

Data presented as median ± SEM * p<0.05 relative to the No pre-treatment group LD = loading dose

Pretreatment=Prasugrel 30 mg/Prasugrel 30 mg; No Pre-treatment=Placebo/Prasugrel 60 mg

Pre LD2 0.5 1 2 3 4 24

Approximate time of PCI

*

*

30 mg LD1

Placebo LD1

60 mg LD2

30 mg LD2

*P<0.05

www.nejm.org - 8.26.12

TRILOGY ACS Study Design Medically Managed UA/NSTEMI Patients

Clopidogrel 1

75 mg MD

Prasugrel 1

5 or 10 mg MD

Minimum Rx Duration: 6 months; Maximum Rx Duration: 30 months

Primary Efficacy Endpoint: CV Death, MI, Stroke

Randomization Stratified by:

Age, Country, Prior Clopidogrel Treatment

(Primary analysis cohort — Age < 75 years)

5 or 10 mg MD

Medical Management Decision ≤72 hrs

(No prior clopidogrel given) — 4% of total

Medical Management Decision ≤ 10 days

(Clopidogrel started ≤ 72 hrs in-hospital OR

on chronic clopidogrel) — 96% of total

1 All patients were on aspirin and low-dose aspirin (< 100 mg) was strongly recommended For patients <60 kg or ≥75 years, 5 mg

MD of prasugrel was given Adapted from Chin CT et al Am Heart J 2010;160:16-22.e1

Median Time to Enrollment = 4.5 Days

Median On-Treatment PRU Through 30 Months

< 75 years and ≥ 60 kg

Prasugrel Clopidogrel

Prasugrel Clopidogrel

Median On-Treatment PRU Through 30 Months

< 75 years and < 60 kg

Median On-Treatment PRU Through 30 Months

Prasugrel Clopidogrel

≥ 75 years

Landmark at 30 Days

HPR Cut-Point > 208 PRU

The P values for each panel compare

the hazard between the two groups

throughout the time period represented

Primary Efficacy Endpoint

With HPR

Without HPR

Death / MI / IDR / ST OR (95% CI) p value

p for interaction

Steg GS, Bhatt DL, Hamm CW et al… Harrington RA Lancet 2013 at www.thelancet.com

Non-CABG Bleeding at 48 Hours, Safety

(N=12,565)

Clopidogrel (N=12,5425) OR (95% CI) P Value

TIMI Major + Minor 109 (0.9%) 79 (0.6%) 1.38 (1.03, 1.85) 0.0290

Any Blood Transfusion 90 (0.7%) 70 (0.6%) 1.29 (0.94, 1.76) 0.1154

ACUITY Major 534 (4.2%) 353 (2.8%) 1.53 (1.34, 1.76) <0.0001

ACUITY w/out hematoma 169 (1.3%) 123 (1.0%) 1.38 (1.09, 1.74) 0.0071

Steg GS, Bhatt DL, Hamm CW et al… Harrington RA Lancet 2013 at www.thelancet.com