Treatment of Acute Coronary Syndrome: A Patient-Centered ... · • Using real patient case scenarios, determine and justify the appropriate dose and duration of antiplatelet therapy

Treatment of Acute Coronary Syndrome: A Patient-Centered,

Guideline-Directed Approach to the Selection and Use of

Antiplatelet Therapy

Presented as a Live Webinar

Wednesday, October 29, 2014 1:00 p.m. – 2:00 p.m. ET

www.ashpadvantage.com/treatacs

Planned and conducted by ASHP Advantage and supported by an educational grant from Daiichi Sankyo, Inc. and Lilly USA, LLC.

http://www.ashpadvantage.com/treatacs

Treatment of Acute Coronary Syndrome: A Patient-Centered, Guideline-Directed Approach to the Selection and Use of Antiplatelet Therapy

Activity Overview

An unacceptable number of people die from acute coronary syndrome (ACS) each year, despite recent treatment advances and the availability of evidence-based treatment guidelines. Although the need for dual antiplatelet therapy in patients with ACS is well established, pharmacists face a number of clinical dilemmas in their quest to optimize therapy. In this presentation, the faculty will review the risks and benefits of current and emerging oral antiplatelet agents and treatment strategies, including those that minimize risk and improve outcomes. Treatment approaches using evidence-based guidelines will be discussed. Using patient case examples and an automated audience response system, faculty will engage participants in the clinical decision-making process involved in addressing challenges related to oral antiplatelet therapy for patients with ACS.

Learning Objectives

At the conclusion of this application-based educational activity, participants should be able to • Describe the differentiating characteristics of currently available oral antiplatelet therapy agents. • Using real patient case scenarios, determine and justify the appropriate dose and duration of

antiplatelet therapy. • Explain how a patient’s comorbidities influence the appropriate selection of an antiplatelet agent and/or

regimen. • Review updated ACS treatment guidelines and explain how they might be incorporated into clinical

practice.

Continuing Education Accreditation

The American Society of Health-System Pharmacists is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This activity provides 1.0 hour (0.1 CEU – no partial credit) of continuing pharmacy education credit (ACPE activity #0204-

0000-14-499-L01-P for the live activity and ACPE activity #0204-0000-14-499-H01-P for the on-demand activity).

Participants will process CPE credit online at http://elearning.ashp.org/my-activities, with the option of printing a CE certificate. CPE credit will be reported directly to CPE Monitor. Per ACPE, CPE credit must be claimed no later than 60 days from the date of the live activity or completion of a home study activity.

Webinar Information

Visit http://www.ashpadvantage.com/treatacs to find: • Webinar registration link • Group viewing information and technical requirements • CPE webinar processing instructions

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http://elearning.ashp.org/my-activities

http://www.ashpadvantage.com/treatacs

http://www.ashp.org/ClaimCE


Additional Educational Activities in this Initiative

This live activity will be archived and offered as web-based on-demand learning at www.ashpadvantage.com/treatacs

Activity Faculty

Zachary Stacy, Pharm.D., M.S., FCCP, BCPS Associate Professor of Pharmacy Practice St. Louis College of Pharmacy St. Louis, Missouri Dr. Zachary Stacy is Associate Professor of Pharmacy Practice at the St. Louis College of Pharmacy. He earned his Bachelor of Science degrees in Chemistry and Biology from Blackburn College and his Masters in Chemistry degree from Southern Illinois University in Edwardsville. Dr. Stacy completed his Doctor of Pharmacy degree at the St. Louis College of Pharmacy and a specialty residency in internal medicine at St. Luke’s Hospital in Chesterfield, Missouri. He is a board-certified pharmacotherapy specialist. Dr. Stacy maintains a clinical practice in cardiology at Mercy Hospital St. Louis.

Dr. Stacy’s didactic responsibilities include ischemic heart disease, heart failure, peripheral arterial disease, and venous thromboembolism at the St. Louis College of Pharmacy. He is an adjunct clinical professor in the Physician Assistant program at Saint Louis University and serves as an ACLS instructor. Dr. Stacy has won numerous teaching awards including the 2005 Excellence in Clinical Precepting, the 2009 Joe E. Haberle Outstanding Educator of the Year Award, and the 2010 Missouri Pharmacy Association Faculty Member of the Year Award.

Dr. Stacy’s primary research interests include the prevention of venous thromboembolism and the management of peripheral arterial disease. He has authored numerous articles, reviews, and book chapters and frequently provides presentations at state, national, and international conferences. He is an active member of numerous pharmacy organizations including the ACCP and ASHP. In 2013, Dr. Stacy was named a Fellow of the American College of Clinical Pharmacy.

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http://www.ashpadvantage.com/treatacs.

http://www.ashpadvantage.com/treatacs.


Disclosure Statement

In accordance with the Accreditation Council for Continuing Medical Education’s Standards for Commercial Support and the Accreditation Council for Pharmacy Education’s Guidelines for Standards for Commercial Support, ASHP Advantage requires that all individuals involved in the development of activity content disclose their relevant financial relationships. A commercial interest is any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. A person has a relevant financial relationship if the individual or his or her spouse/partner has a financial relationship (e.g., employee, consultant, research grant recipient, speakers bureau, or stockholder) in any amount occurring in the last 12 months with a commercial interest whose products or services may be discussed in the educational activity content over which the individual has control. The existence of these relationships is provided for the information of participants and should not be assumed to have an adverse impact on presentations.

All faculty and planners for ASHP Advantage education activities are qualified and selected by ASHP Advantage and required to disclose any relevant financial relationships with commercial interests. ASHP Advantage identifies and resolves conflicts of interest prior to an individual’s participation in development of content for an educational activity.

• Zachary Stacy, Pharm.D., M.S., FCCP, BCPS, declares that he has served as a consultant for Janssen

Pharmaceuticals, Inc., and AstraZeneca. • All other planners report no financial relationships relevant to this activity.

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Zachary Stacy, Pharm.D., M.S., FCCP, BCPS

Associate Professor of Pharmacy Practice St. Louis College of Pharmacy

St. Louis, Missouri

Planned and coordinated by ASHP Advantage and supported by an educational grant from Daiichi Sankyo, Inc. and Lilly USA, LLC.

• Zachary Stacy, Pharm.D., M.S., FCCP, BCPS, declares that he has served as a consultant for Janssen Pharmaceuticals, Inc., and AstraZeneca.

• All other planners report no financial relationships relevant to this activity.

Disclosures

Learning Objectives• Describe the differentiating characteristics of currently

available oral antiplatelet therapy agents.

• Using real patient case scenarios, determine and justify the appropriate dose and duration of antiplatelet therapy.

• Explain how a patient’s comorbidities influence the appropriate selection of an antiplatelet agent and/or regimen.

• Review updated ACS treatment guidelines and explain how they might be incorporated into clinical practice.

Patient CasePMI: A 66-year-old woman presents to the ED with chest

pain consistent with NSTEMI. She undergoes cardiaccatheterization and receives a DES in the LAD. Her post-catheterization recovery was complicated with paroxysmal atrial fibrillation. The team needs your help in preparing the patient for discharge.

PMH: Gout x 15 yearsPUD x 10 yearsCAD s/p NSTEMI x 48 hoursNew onset atrial fibrillation x 24 hours

Meds: Omeprazole 20 mg PO dailyAllopurinol 300 mg PO daily

Which of the following therapies should be initiated upon discharge to prevent stent thrombosis?

a. Ticlopidine 250 mg PO twice daily for 10 months

b. Clopidogrel 75 mg PO daily for 1 yearc. Prasugrel 10 mg PO daily for at least 1

yeard. Ticagrelor 90 mg PO twice daily for at

least 15 months

Currently Available Oral Antiplatelet Options

• Aspirin• P2Y12 Inhibitors

– Thienopyridines• Clopidogrel• Prasugrel• Ticlopidine

– Cyclopentyl-triazolopyrimidine• Ticagrelor

• Protease-activated receptor-1 antagonist – Vorapaxar

5

FDA-Approved Antiplatelet Agents

1992 1994 1996 1998 2000 2002 2004 2006 2008 2010

Glycoprotein IIb/IIIa Inhibitors

Abciximab

12-16-1993

Clopidogrel

11-17-1997

P2Y12 Inhibitors

Prasugrel

7-10-2009

Tirofiban

5-14-1998

Eptifibatide

5-18-1998

Ticlopidine

10-31-1991

Ticagrelor

6-20-2011

P2Y12 Inhibitors

Prasugrel

Clopidogrel

Ticagrelor

Ticlopidine

FDA-Approved Indications

Clopidogrel Prasugrel Ticagrelor

UA/NSTEMI X X X

STEMI X X X

Stroke X

Peripheral arterial disease X

Plavix (clopidogrel) prescribing information. Bristol-Myers Squibb/Sanofi Pharmaceuticals. 2013 Dec.Effient (prasugrel) prescribing information. Eli Lilly and Company. 2013 Nov.

Brilinta (ticagrelor) prescribing information. AstraZeneca, Inc. 2013 Dec.

Traditional Antiplatelet Agent Limitations

• Adverse effects (i.e., bleeding)

• Drug-drug interactions

• Unpredictable responses

• Unreliable monitoring

• Delayed onset and offset

• Reversibility

P2Y12 Inhibitor Comparison

Adverse Effects Clopidogrel Ticagrelor Prasugrel

Bleeding X X X

Hyperuricemia X

Dyspnea X

>50% ↑ in SCr X

Ventricular pauses X



P2Y12 Inhibitor Comparison

Cautions:

• Prasugrel: body weight <60 kg; Age ≥75

• Ticagrelor: uncontrolled gout

Contraindications Clopidogrel Ticagrelor Prasugrel

Life-threatening hemorrhage X X X

History of stroke or TIA X

Concomitant 2C19 inhibitors X

Concomitant strong 3A4 inhibitors and inducers

X

Poor metabolizer: CYP2C19*2 or CYP2C19*3

X

Aspirin doses >100 mg daily X

Severe hepatic impairment –Child Pugh C

X

6

Comparison of Antiplatelet Agents

Clopidogrel Prasugrel Ticagrelor

Molecular weight 419.9 Da 410 Da 523 Da

Protein binding 98% 98% >99%

Volume of distribution 44-68L 88L

Binding to catalytic site Irreversible Irreversible Reversible

Activation Prodrug ProdrugNot

required



Learning Objectives

At the conclusion of this educational activity, participants

should be able to

• Describe the differentiating characteristics of currently available oral antiplatelet therapy agents

• Using real patient case scenarios, determine and justify the appropriate dose and duration of antiplatelet therapy

• Explain how a patient’s comorbidities influence the appropriate selection of an antiplatelet agent and/or regimen

• Review updated ACS treatment guidelines and explain how they might be incorporated into clinical practice

Clopidogrel 75 mg daily + ASA 75-325 mg daily

(6259 patients)

Placebo + ASA 75-325 mg daily

(6303 patients)

Patients withUA/NSTEMI

Yusef S et al. N Engl J Med. 2001; 345:494-502.

CURE Trial

Double-blind, mean treatment of 9 monthsR

Primary endpoint: non-fatal MI, stroke, and CV death

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

Cum

ulat

ive

Haz

ard

Rat

e(M

I/S

trok

e/C

V D

eath

)

Clopidogrel+ ASA

3 6 9

Placebo + ASA

Months

20% RRR p = 0.00009N = 12,562

0 12

11.4%

9.3%


CURE Trial

0.15

0.10

0.05

0.00 100 200 300 400

Days

12.6%

8.8%

31% RRR p = 0.002N = 2,658

Clopidogrel+ ASA

Placebo+ ASA

Cum

ulat

ive

Haz

ard

Rat

e

(MI

or C

V D

eath

)


CURE Trial: PCI-CURE Results

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CURE Sub-Analysis – Diabetes

• Patients with DM at baseline (n=2840)

• Primary endpoint (composite of stroke, MI, and death from vascular causes)– Clopidogrel = 14.2%

– Placebo = 16.7%


CURE Sub-Analysis – Elderly

• Patients age >65 years (n=6208)


– Placebo = 15.3%


CURE Sub-Analysis – STEMI

• Patients with ST deviation (n=6275)


– Placebo = 14.3%


Clopidogrel 300 mg LD followed by clopidogrel 75 mg daily

(6795 patients)

Prasugrel 60 mg LD followed by prasugrel 10 mg daily

(6813 patients)

Patients withUA/NSTEMI (TIMI

risk score >3)

or STEMI and a planned PCI

TRITON-TIMI 38 Trial

Long-term ASA 75–162 mg daily was recommended for all patients

Mean treatment follow-up of 14.5 monthsR

Wiviott SD et al. Am Heart J. 2006; 152:627-35. Wiviott SD et al. N Engl J Med. 2007; 357:2001-15.

Primary efficacy endpoint: non-fatal MI, stroke, and CV deathPrimary safety endpoint: TIMI major and minor bleeding, and life-threatening bleeding

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81(0.73-0.90)

p<0.001

Prasugrel

Clopidogrel

HR 0.80P<0.001

Days

Com

posi

te E

ffic

acy

End

poin

t (C

V d

eath

, no

n-fa

tal M

I, o

r no

n-fa

tal s

trok

e)

12.1%

9.9%

Wiviott SD et al. N Engl J Med. 2007; 357:2001-15.


HR 0.77P<0.001

Days

Prim

ary

Saf

ety

End

poin

t

(TIM

I M

ajor

Non

-CA

BG

ble

edi

ng)

0

0 30 60 90 180 270 360 450

HR 1.32(1.03-1.68)

p=0.03

Prasugrel

Clopidogrel

1.8%

2.4%

4

2

1

3

Wiviott SD et al. N Engl J Med. 2007; 357:2001-2015.


8

1.8

0.9 0.9

0.10.3

2.4

1.4

1.1

0.4 0.3

0

0.5

1

1.5

2

2.5

3

Non-CABGTIMI Major

Bleeds

LifeThreatening

Non-Fatal Fatal ICH

Clopidogrel

Prasugrel

ARD 0.6% ARD 0.5% ARD 0.2% ARD 0.3% ARD 0%HR 1.32 HR 1.52 HR 1.25 HR 4.19 HR 1.12p=0.03 p=0.01 p=0.23 p=0.002 p=0.74


Saf

ety

End

poin

ts (

%)

TRITON-TIMI 38 TrialEndpoints Prasugrel

(n=6,741)Clopidogrel

(n=6,716) HR (95% CI) P-value

History of Stroke or TIA

CV Death, MI, Stroke 19.1 14.4 1.37 (0.89 to 2.13) 0.15

Non-CABG TIMI Major Bleed 5.0 2.9 2.46 (0.94 to 6.42) 0.06

All-cause death, MI, stroke, or non-CABG related non-

fatal TIMI major bleed23.0 16.0 1.54 (1.02 to

2.32) 0.04

No History of Stroke or TIA

CV death, MI, stroke 9.5 12.0 0.79 (0.71 to 0.88) <0.001

Non-CABG TIMI major bleed 2.3 1.8 1.26 (0.97 to 1.62) 0.08

All-cause death, MI, stroke, or non-CABG related non-

fatal TIMI major bleed11.8 13.8 0.84 (0.76 to

0.93) <0.001

Boxed Warning: Prasugrel should not be used in patients with any history of stroke

Patient CasePMI: A 62-year-old man presents to the ED with chest

pain consistent with STEMI. He undergoes a PCI and has a DES placed. His procedure had no complications. The team needs your help in preparing the patient for discharge.

PMH: HTN x 21 yearsHLD x 17 yearsHepatic Impairment (Child Pugh C) x 14 yearsCAD s/p STEMI x 12 hours

Meds: Lisinopril 10 mg PO dailyAtorvastatin 20 mg PO daily


a. Ticlopidine 250 mg PO twice daily

b. Clopidogrel 75 mg PO daily

c. Prasugrel 10 mg PO daily

d. Ticagrelor 90 mg PO twice daily

TRITON Sub-Analysis – STEMI

Endpoints Clopidogrel Prasugrel HR 95% CI p-value

Primary endpoint (composite of stoke,

MI, and death of vascular causes)

9.5% 6.5% 0.68 0.54 – 0.87 0.0017

Secondary endpoint (stent thrombosis)

2.4% 1.2% 0.49 0.28 – 0.85 0.0084

Safety endpoint (TIMI-defined major

bleed)1.3% 1.0% 0.74 0.39 – 1.38 0.3359

Montalescot G et al. Lancet. 2009; 373:723-31.

(N=7544)

Clopidogrel 300 mg LD followed by clopidogrel 75 mg daily

(9291 patients)

Ticagrelor 180 mg LD followed by ticagrelor 90 mg twice daily

(9333 patients)

Patients withUA/NSTEMI or

STEMI

PLATO Trial

Long-term ASA 75–325 mg daily was recommended for all patients

Mean treatment follow-up of 9 monthsR

Primary efficacy endpoint: non-fatal MI, non-fatal stroke, and CV deathPrimary safety endpoint: major bleeding

Wallentin L et al. N Engl J Med. 2009; 361:1045-57.

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PLATO TrialEndpoints Ticagrelor Clopidogrel CI (95%CI) P-valueComposite endpoint (%)

9.8 11.7 0.84 (0.77-0.92) 0.0003

CV death (%) 2.9 4.0 0.74

Non-fatal MI (%) 5.8 6.9 0.84

Non-fatal stroke (%) 1.4 1.1 1.24

Secondary endpoints

CV death (%) 4.0 5.1 0.79 (0.69-0.91) 0.0013

MI (%) 5.8 6.9 0.84 (0.75-0.95) 0.0045

Stroke (%) 1.5 1.3 1.17 (0.91-1.52) 0.22

All-cause mortality (%) 4.5 5.9 0.78 (0.69-0.89) 0.0003

Wallentin L et al. N Engl J Med. 2009; 361:1045-57.Marciniak TA. Food and Drug Administration. Ticagrelor for acute coronary syndromes, NDA 22-433. June 29, 2010.

PLATO Trial

Country Aspirin Daily Dose

TicagrelorEvents

ClopidogrelEvents HR

U.S. sites

>300 mg 324 352 1.62 (0.99-2.64)

100 mg – 300 mg

22 16

<100 mg 284 263 0.73 (0.40-1.33)

Non-U.S.sites

>300 mg 140 140 1.23 (0.71-2.14)

100 mg – 300 mg

503 511 1.00 (0.71-1.42)

<100 mg 7449 7443 0.78 (0.69-0.87)

Boxed Warning: Ticagrelor should not be used with aspirin doses >100 mg daily

PLATO Trial

Bleeding Ticagrelor Clopidogrel

Major and minor bleeding 8.7% 7.0%

Major bleeding 4.5% 3.8%

Fatal or life-threatening bleeding 2.1% 1.9%

Fatal bleeding 0.2% 0.2%

Intracranial bleeding 0.3% 0.2%


PLATO TrialAdverse Drug

Reactions Ticagrelor Clopidogrel P Value

Dyspnea 13.8% 7.8% p<0.05

Syncope, pre-syncope, and

loss of consciousness1.7% 1.5% NS

Ventricular pauses (<1 month from initiation)

6.0% 3.5% p<0.05

Ventricular pauses (>1 month from initiation)

2.2% 1.6% NS

Uric acid + 0.6 mg/dL + 0.2 mg/dL p<0.05

Gout exacerbations 0.6% 0.6% NS

Increased serum creatinine

7.4% 5.9% p<0.05


Patient CasePMI: A 68-year-old woman presented to the ED with chest

pain consistent with STEMI. She underwent a primary PCI and a DES is placed. An electrocardiogram captured 1st-degree heart block following the procedure. The team needs your help in preparing the patient for discharge, and they ask for your recommendation.

PMH: Stroke 10 years agoCAD s/p STEMI x 12 hoursCHF x 25 yearsDM x 45 years

Meds: Lisinopril 20 mg PO dailyCarvedilol 25 mg PO BIDMetformin 1000 mg PO BID

10


a. Ticlopidine 250 mg PO twice daily

b. Clopidogrel 75 mg PO daily

c. Prasugrel 10 mg PO daily

d. Ticagrelor 90 mg PO twice daily

PLATO Sub-Analysis – Diabetes

(n=4662)

Endpoints Ticagrelor Clopidogrel HR 95% CI p-value

Primary endpoint (composite of

stroke, MI, and death from

vascular causes)

14.1% 16.2% 0.880.76 –1.03

0.49

Safety endpoint (PLATO-defined

major bleed)9.0% 9.9% 1.07

0.74 –1.10

0.10

James S et al. Eur Heart J. 2010; 31:3006-16.

PLATO Sub-Analysis – Elderly

(n=2878)



stroke, MI, anddeath from

vascular causes)

17.2% 18.3% 0.89 0.74 – 1.08 0.56


major bleed)1.8% 2.1% 1.02 0.82 – 1.27 0.89

Husted et al. Circ Cardiovasc Qual Outcomes. 2012; 5:680-8.

PLATO Sub-Analysis – STEMI

(n=7544)




vascular causes)

10.8% 9.4% 0.87 0.75 – 1.01 0.07


major bleed)9% 9.2% 0.98 0.83 – 1.14 0.76

Steg PG et al. Circulation. 2010; 122:2131-41.

PLATO Sub-Analysis – STEMISecondary Endpoints Ticagrelor Clopidogrel HR 95% CI p-value

Non-procedurerelated major

and minor bleed5.1% 3.7% 1.31

1.04 –1.66

0.02

MI alone 4.7% 5.8% 0.800.65 –0.98

0.03

Definite stent thrombosis

1.6% 2.4% 0.660.45 –0.95

0.03

Stroke alone 1.7% 1.0% 1.631.07 –2.48

0.02

Steg PG et al. Circulation. 2010; 122:2131-41.

PLATO Sub-Analysis – CKD

(n=3237)




vascular causes)

17.3% 22% 0.77 0.79 – 1.02 0.13


major bleed)15.1% 14.3% 1.07 0.88 – 1.30 0.92

James S et al. Circulation. 2010; 122:1056-67.

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Safety Outcomes Overview

CURE Trial TRITON Trial PLATO Trial

Major bleed, TIMI-defined

Clopidogrel: 3.7%Placebo: 2.7%

p=0.001RR: 1.38 (1.13-1.67)

Clopidogrel: 2.1%Prasugrel: 2.4%

p=0.6451HR: 1.11 (0.70-1.77)

Ticagrelor: 7.9%Clopidogrel: 7.7%

p=0.57HR: 1.03 (0.93-1.15)

Life-threatening

bleed


p=0.13RR: 1.21 (0.95-1.56)

Clopidgrel: 1.1%Prasugrel: 1.3%

p=0.7500HR: 1.11 (0.59-2.10)


p=0.70HR: 1.03 (0.90-1.16)

Requiring 2 units of blood transfusion


p=0.02Did not have data


p=0.96HR: 1.00 (0.91-1.11)

Learning Objectives

At the conclusion of this educational activity, participants

should be able to

• Describe the differentiating characteristics of currently available oral antiplatelet therapy agents

• Using real patient case scenarios, determine and justify the appropriate dose and duration of antiplatelet therapy

• Explain how a patient’s comorbidities influence the appropriate selection of an antiplatelet agent and/or regimen

• Review updated ACS treatment guidelines and explain how they might be incorporated into clinical practice

Anti-Platelet Therapy | NSTEMI Guidelines

Clinical Scenario Drug Bolus

DoseMaintenance

DoseAHA/ACC

Class/ LOE

Medical Management

(DAPT)

Aspirin 162-325 mg 81-162 mg dailyClass ILOE A

Clopidogrel

Ticagrelor

300-600 mg

180 mg

75 mg daily

90 mg BID

Class ILOE B

PCI with Stenting(DAPT)

Aspirin 325 mg 81-162 mg dailyClass ILOE B

Clopidogrel

Prasugrel

Ticagrelor

300-600 mg

60 mg

180 mg

75 mg daily

10 mg daily

90 mg BID

Class ILOE B

Amsterdam EA et al. Circulation. 2014 Sep 23. [Epub ahead of print]

DAPT = dual antiplatelet therapy (aspirin plus P2Y12 inhibitor)LOE = level of evidence

Anti-Platelet Therapy | NSTEMI Guidelines

Recommendation AHA/ACC Class/ LOE

Ticagrelor in preference to clopidogrel for patients treated with an early invasive or ischemia-guided strategy

Class IIa; LOE B

P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) continued for at least 1 year in post–PCI patients treated

with coronary stentsClass I; LOE B

PCI = percutaneous coronary interventionLOE = level of evidence

Amsterdam EA et al. Circulation. 2014 Sep 23. [Epub ahead of print]

Anti-Platelet Therapy | STEMI GuidelinesAspirin

Recommendation Primary PCI FibrinolyticTherapy

162-325 mg loading dose Class I; LOE B Class I; LOE A

81-325 mg maintenance dose Class I; LOE A Class I; LOE A

81 mg preferred maintenance dose Class IIa; LOE B Class IIa; LOE B

O'Gara PT et al. Circulation. 2013;127:529-555.


Anti-Platelet Therapy | STEMI GuidelinesP2Y12 Loading Doses

Recommendation Primary PCI FibrinolyticTherapy

Clopidogrel 300 mg Not recommended<75 years oldClass I; LOE A

Clopidogrel 600 mg Class I; LOE B Not recommended

Prasugrel 60 mg Class I; LOE B Not recommended

Ticagrelor 180 mg Class I; LOE B Not recommended



12

Anti-Platelet Therapy | STEMI GuidelinesP2Y12 Maintenance Doses

RecommendationPrimary PCI

BMS and DES At least 1 year

Primary PCIDES

Beyond 1 year

FibrinolyticTherapy

Clopidogrel 75 mg daily Class I; LOE B Class IIb; LOE C

At least 14 daysClass I; LOE A

At least 1 yearClass I; LOE C

Prasugrel 10 mg daily Class I; LOE B Class IIb; LOE C Not recommended

Ticagrelor 90 mg BID Class I; LOE B Class IIb; LOE C Not recommended


BMS = bare metal stentDES = drug eluting stentPCI = percutaneous coronary interventionLOE = level of evidence

Aspirin (98%) and thienopyridine therapy (78%)

(13,224 patients)

Vorapaxar 2.5 mg daily + standard of care(13,225 patients)

Patients withMI, CVA, or PAD

TRA 2P-TIMI 50 Trial

R

Morrow DA et al. N Engl J Med. 2012; 366:1404-13.

Primary efficacy endpoint: CV death, MI, stroke, and recurrent ischemia.Primary safety endpoint: GUSTO bleeding (GUSTO and TIMI bleeding)

MI = 67%Stroke = 18.5%PAD = 14.5%

TRA 2P-TIMI 50 Trial

Endpoints Vorapaxar Placebo HR 95% CI p-value

Primary endpoint (composite of CV

death, MI, stroke, and recurrent ischemia)

11.2% 12.4% 0.88 0.82-0.95 0.001

Secondary endpoint (composite of CV

death, MI, and stroke)9.3% 10.5% 0.87 0.80-0.94 <0.001

Safety endpoint (GUSTO bleeding)

4.2% 2.5% 1.66 1.36-1.57 <0.001

Safety endpoint (TIMI bleeding)

15.8% 11.1% 1.46 1.36-1.57 <0.001

Net clinical outcome(Death, MI, stroke, or

GUSTO bleeding)11.9% 12.8% 0.92 0.85-0.99 0.02

Morrow DA et al. N Engl J Med. 2012; 366:1404-13.

Final Points• New guidelines!

– Amsterdam EA et al. 2014 ACC/AHA guideline for the management of patients with non–ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Sep 23 [Epubahead of print]

• Consider drug-drug interactions, drug-disease interactions, and contraindications with newer anti-platelet agents.

• New therapies should be consider the following special populations:– Elderly– STEMI– Diabetics– Renal disease

13


Self-assessment Questions

1. Which of the following therapies should be initiated upon discharge to prevent stent thrombosis?

a. Ticlopidine 250 mg PO twice daily for 10 months b. Clopidogrel 75 mg PO daily for 1 year c. Prasugrel 10 mg PO daily for at least 1 year d. Ticagrelor 90 mg PO twice daily for at least 15 months


a. Ticlopidine 250 mg PO twice daily b. Clopidogrel 75 mg PO daily c. Prasugrel 10 mg PO daily d. Ticagrelor 90 mg PO twice daily


a. Ticlopidine 250 mg PO twice daily b. Clopidogrel 75 mg PO daily c. Prasugrel 10 mg PO daily d. Ticagrelor 90 mg PO twice daily

Answers

1. c 2. c 3. b

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Treatment of Acute Coronary Syndrome: A Patient‐Centered, Guideline‐Directed Approach to the Selection and Use of Antiplatelet Therapy

Abbreviations list

CAD – coronary artery disease

CHF – congestive heart failure

DES – drug‐eluting stent

DM – diabetes mellitus

ED – Emergency Department

DES – drug‐eluting stent

HLD – hyperlipidemia

HTN – hypertension

IPA – inhibition of platelet aggregation

LOE – level of evidence

NSTEMI – non‐ST segment elevation myocardial infarction

PCI – percutaneous coronary intervention

PUD – peptic ulcer disease

STEMI – ST segment elevation myocardial infarction

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Documents

Treatment of Acute Coronary Syndrome: A Patient-Centered ... · • Using real patient case scenarios, determine and justify the appropriate dose and duration of antiplatelet therapy