dapt: it get here?

Christopher Betz, Pharm.D., BCPS, FKSHP, FASHPProfessorSullivan University College of Pharmacy

Snehal H. Bhatt, Pharm.D., BCPSAssociate ProfessorMCPHS University

Does Practice Need to a‐DAPT? Considerations in Antiplatelet Therapy after Drug‐Eluting Stent Implantation

Disclosure• We have no real or perceived conflict of

interest related to the content of thispresentation

Learning Objectives• Discuss the current guideline recommendations for using

dual antiplatelet therapy (DAPT) following drug‐eluting stent implantation

• Interpret the clinical trial evidence that supports the use ofDAPT for one year

• Evaluate the clinical trial data evidence that refutes the useof DAPT for one year

• Design an evidence based DAPT regimen in a complex patient following drug‐eluting stent implantation

Question 1RB is a 68‐year‐old man who presents with NSTEMI and is managed medically after PCI because he showed no obvious location for stent placement. Which of the following antiplatelet therapy regimen would you recommend?

Aspirin 81 mg daily

Aspirin 325 mg daily

Aspirin 81 mg daily plus clopidogrel

Aspirin 325 mg daily plus clopidogrel

Question 2Based on clinical trial data, which of the following outcomes are expected in RB if he receives DAPT versus aspirin alone?

Reduced risk of death; no difference in major bleeding

Reduced risk of MI; no difference in major bleeding

Reduced risk of death; increased risk of major bleeding

Reduced risk of MI; increased risk of major bleeding

DAPT: How did it get here?

2015 ASHP Midyear Clinical MeetingDoes Practice Need to a-DAPT? Considerations in Antiplatelet Therapy after Drug-Eluting Stent Implantation

© 2015 American Society of Health-System Pharmacists 1

CURENSTEMI presenting within 24 hours of symptom onset

(n = 12562)NSTEMI presenting within 24 hours of symptom onset

(n = 12562)

Primary endpoint: CV death + stroke + MIMean follow‐up: 9 months

Primary endpoint: CV death + stroke + MIMean follow‐up: 9 months

Clopidogrel 300mg load then 75mg daily + aspirin 75‐325 mg daily for 3‐12 months

(n=6259)

Clopidogrel 300mg load then 75mg daily + aspirin 75‐325 mg daily for 3‐12 months

(n=6259)

Placebo + aspirin 75‐325 mg daily(n= 6303)

Placebo + aspirin 75‐325 mg daily(n= 6303)

Yusuf S, et al. Eur Heart J. 2000;21:2033‐41The CURE Trial Investigators. N Engl J Med. 2001;345:494‐502

CURE: Baseline characteristicsClopidogrel (%) Placebo (%)

Age (mean, year) 64.2 64.2

Female 38.7 38.3

Unstable Angina 74.9 74.9

NSTEMI 25.1 25.1

History of MI 32.4 32

Diabetes 22.4 22.8

Current or former smoker 60.6 60.9

CABG Surgery 17.7 18.1

Stroke 4.4 3.7

The CURE Trial Investigators. N Engl J Med. 2001;345:494‐502.

CURE: Efficacy resultsOutcome Clopidogrel Placebo RRR p value

CV death/MI/Stroke(primary endpoint)

9.3% 11.8% 20% < 0.001

MI 5.2% 6.7% 23% < 0.001

Stroke 1.2% 1.4% 14% NS

CV Death 5.1% 5.5% 7% NS


Number needed to treat to prevent one primary endpoint event = 40

patients for 9 months

CURE: Safety results

Endpoint Clopidogrel Placebo p value

Major bleeding 3.7% 2.7% 0.001

Life‐threatening bleeding 2.2% 1.8% NS

Non life‐threatening bleeding 1.5% 0.9% 0.002

Minor bleeding 5.1% 2.4% <0.001

Transfusion of ≥ 2 units blood 2.8% 2.2% 0.02

Total bleeding complications 8.5% 5% <0.001


Number needed to harm = 100Major bleeding episodes were defined as substantially disabling bleeding, intraocular bleeding leading to the loss of vision, or bleeding necessitating the transfusion of at least 2 units of blood.

Minor bleeding: other hemorrhages that led to interruption of study medication

CURE: Life‐threatening bleedingClopidogrel Placebo

Life‐threatening 2.2% 1.8%

Fatal bleeding 0.2% 0.2%

Hemoglobin drop > 5 g/dL 0.9% 0.9%

Hypotension requiring inotropes 0.5% 0.5%

Hemorrhagic stroke 0.1% 0.1%

Surgery required 0.7% 0.7%

Received > 4 units of blood 1.2% 1.0%


CURE: Conclusions• Clopidogrel use associated with a 20% RRR in

the primary endpoint– Driven by reduction in MI

• Major bleeding increased by 38% – No difference in life‐threatening bleeding– Minor and total bleeding were significantly

increased


2015 ASHP Midyear Clinical Meeting Does Practice Need to a-DAPT? Considerations in Antiplatelet Therapy after Drug-Eluting Stent Implantation


(PCI)‐CURE• Prospectively designed study of patients

undergoing PCI who were already enrolled in the CURE trial (n=2658)

• Objectives:– Pre‐treatment with clopidogrel + ASA would be

better than ASA alone in preventing ischemic events at 30 days in patients undergoing PCI

– Determine if long‐term therapy with clopidogrel + ASA would provide additional clinical benefit vs. ASA alone

Mehta SR et al. Lancet. 2001;358: 527‐33.

PCI‐CURE: Study Design• Patients randomized to clopidogrel or placebo at CURE trial entry, both in

addition to aspirin and standard therapy

• All patients undergoing PCI during the course of the CURE trial were included in PCI‐CURE

• Timing of PCI was at the physician’s discretion

• At time of PCI, study drug was interrupted and open‐label therapy was initiated for 2‐4 weeks

• During open‐label therapy, clopidogrel in combination with ASA was permitted

• Follow‐up ranged from 3‐12 months


PCI‐CURE: Endpoints• Composite of the following at 30 days:

– CV Death– MI– Urgent target vessel revascularization

• Composite of the following from PCI to the end of follow‐up:– CV Death– MI


PCI‐CURE: BackgroundClopidogrel Placebo

Overall median # days from randomization to PCI 10 days 10 days

PCI during hospitalization 6 days 6 days

PCI after initial hospitalization 49 days 49 days

Stent use (%) 82.4 81.3

Open‐label thienopyridine before PCI (%) 24.6 24.7

Overall use of open‐label thienopyridine(%) 82.9 84.1


PCI‐CURE: Results• Primary endpoint: PCI to 30 days:

– 4.5% clopidogrel vs. 6.4% placebo– 30 % relative‐risk reduction, p = 0.03

• Primary endpoint: PCI to follow‐up (12 months): – 6% clopidogrel vs. 8% placebo– 25% relative‐risk reduction, p = 0.047

• Overall long‐term results: from randomization to follow‐up– 8.8% clopidogrel vs. 12.6% placebo– 31% relative‐risk reduction, p = 0.002


PCI‐CURE: Safety• From PCI to 30 days ‐ No significant differences

in:– Major bleeding: 1.6% vs. 1.4%– Life‐threatening bleeding: 0.7% vs. 0.7%– Minor bleeding: 1% vs. 0.7%

• From PCI to the end of follow‐up:– Major bleeding: 2.7% vs. 2.5% (p=NS)– Life‐threatening bleeding: 1.2% vs. 1.3% (p=NS)– Minor bleeding: 3.5% vs. 2.1% (p=0.03)




PCI‐CURE: Conclusions• Clopidogrel plus aspirin demonstrated a 31% relative risk

reduction from randomization to the end of follow‐up (P = 0.002)

• Clopidogrel plus aspirin demonstrated a 25% relative risk reduction in the composite of MI or cardiovascular death withlong‐term use from PCI to end of follow‐up (P = 0.04)

• Long‐term administration of clopidogrel plus aspirin resulted inan overall 25% relative risk reduction in MI and CV death from PCI to end of follow‐up

• There was an increase in minor bleeding, but was no significant difference in major or life‐threatening bleeding between the two treatment groups


Guideline Recommendations

Case• BA is a 76‐year‐old obese white female who

presented to the ED yesterday with intermittentsubsternal chest pain lasting about 20 minutesper episode, which awakened her from sleep.

• The chest pain began to subside with the 3rd doseof 0.4 mg sublingual nitroglycerin administeredby EMS on the way to the ED. In the ED the ECGshowed 1 mm of ST‐segment depression whilethe initial troponin T measurement was negative.The patient provided informed consent for PCI.

Case• Past Medical History

– Hypertension– CVA 10 years ago– GI Bleed 9 years ago

• Social History– Tobacco: 60 pack‐year

• Allergies– NKDA

• Home Medications– Lisinopril 10 mg PO daily– Aspirin 325 mg PO daily– Pravastatin 40 mg PO daily

• PCI– Standard PCI protocol(loaded

with P2Y12 inhibitor)– XIENCE Alpine Everolimus

Eluting Coronary Stent placed in the LAD

– Aspirin 81 mg PO daily post PCI

Question 3According to the current ACC/AHA guidelines, which would be the most appropriate secondary antiplatelet regimen in BA?

Clopidogrel 75 mg PO daily for 12 months

Prasugrel 5 mg PO daily for 3 months

Prasugrel 10 mg PO daily for ≥ 12 months

Ticagrelor 90 mg PO BID for 6 months

ACC/AHA: Classification of Recommendations and Levels of Evidence

A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

*Data available from clinical trials or registries about the usefulness/ efficacy indifferent subpopulations, such as sex, age, history ofdiabetes, history of prior myocardial infarction, history of heart failure, andprior aspirin use.

†For compara. ve effectiveness recommendations (Class I and IIa; Level of Evidence Aand B only), studies thatsupport the use ofcomparator verbs shouldinvolve direct comparisonsof the treatments or strategies being evaluated.

O’Gara PT et al. J Am Coll Cardiol. 2013;61:e78‐140.



Enlarged slide at back of handout.

Duration of DAPT per STEMI Guideline


I IIa IIb III

I IIa IIb IIIContinuation of a P2Y12 inhibitor beyond 1 year may be considered in patients undergoing DES placement.

P2Y12 inhibitor therapy should be given for 1 year to patients with STEMI treated with coronary stents during primary PCI using the following maintenance doses:

• Clopidogrel 75 mg daily; or

• Prasugrel 10 mg daily; or

• Ticagrelor 90 mg twice a day

Duration of DAPT per NSTEMI Guideline

Amsterdam E, et al. J Am Coll Cardiol. 2014;64:e139‐228

I IIa IIb III P2Y12 inhibitor therapy should be given for at least 1 year to post PCI patients treated with coronary stents using the following maintenance doses:• Clopidogrel 75 mg daily; or• Prasugrel 10 mg daily; or • Ticagrelor 90 mg twice a day

I IIa IIb III P2Y12 inhibitor therapy should be given for up to 1 year in patients who do not receive coronary stents using the maintenance doses:• Clopidogrel 75 mg daily; or • Ticagrelor 90 mg twice a day

I IIa IIb III Continuation of a P2Y12 inhibitor beyond 1 year may be considered in patients undergoing stent implantation

Duration of DAPT per PCI Guideline

Levine G, et al. J Am Coll Cardiol. 2011;58:e44‐122

I IIa IIb III

I IIa IIb III

P2Y12 inhibitor therapy should be given for at least 1 year to post PCI patients treated with coronary stents for ACS, using the following maintenance doses:• Clopidogrel 75 mg daily; or• Prasugrel 10 mg daily; or • Ticagrelor 90 mg twice a day

Continuation of DAPT beyond 12 months may be considered in patients undergoing DES placement

Clopidogrel should given to patients receiving drug‐eluting stents for a non‐ACS indication for at least 12 months if the patients are not at high risk of bleeding; or in patients receiving bare metal stents for a non‐ACS indication for a minimum of 1 month, but ideally for 12 months• If the patient received a bare metal stent and is at increased risk of

bleeding then clopidogrel should be given for a minimum of 2 weeks

I IIa IIb III

Question 4According to the current European Society of Cardiology (ESC) Guideline, which would be the most appropriate secondary antiplatelet regimen in BA?

Clopidogrel 75 mg PO daily for 12 months

Prasugrel 5 mg PO daily for 3 months

Prasugrel 10 mg PO daily for ≥ 12 months

Ticagrelor 90 mg PO BID for 6 months

Duration of DAPT per ESC Guideline: STEMI

Windecker S, et al. Eur Heart J. 2014;35:2541‐2619

I IIa IIb III A P2Y12 inhibitor, in addition to lifetime aspirin therapy, should be maintained over 1 year unless there are contraindications such as excessive bleeding. Options include:

• Prasugrel (60 mg load, 10 mg daily) unless contraindicated

• Ticagrelor (180 mg load, 90 mg twice daily) unless contraindicated

• Clopidogrel (600 mg load, 75 mg daily) only when prasugrel or ticagrelor are not available or are contraindicated

I IIa IIb III

Duration of DAPT per ESC Guideline: NSTEMI

Roffi M, et al. Eur Heart J. Published online 29 August 2015.

I IIa IIb III A P2Y12 inhibitor, in addition to lifetime aspirin therapy, should be maintained over 1 year unless there are contraindications such as excessive bleeding. Options include:

• Prasugrel (60 mg load, 10 mg daily) in patients in whom coronaryanatomy is known and who are proceeding to PCI unless contraindicated

• Ticagrelor (180 mg load, 90 mg twice daily) for moderate‐to‐high riskischemic risk patients regardless of initial pretreatment strategy including those pre‐treated with clopidogrel unless contraindicated

• Clopidogrel (600 mg load, 75 mg daily) only when prasugrel or ticagrelor are not available or are contraindicated or who require oral anticoagulation

I IIa IIb III



Duration of DAPT per ESC Guideline: NSTEMI

Roffi M, et al. Eur Heart J. Published online 29 August 2015.

I IIa IIb IIIP2Y12 inhibitor administration for a shorter duration of 3 ‐ 6 months after DES implantation may be considered in patients deemed at a high bleeding risk

P2Y12 inhibitor administration in addition to aspirin beyond 1 year may be considered after careful assessment of ischemic and bleeding risk of the patient

I IIa IIb III

Key Questions?• Can the type of drug‐eluting stent utilized

have an effect on patient outcomes?

• Can the secondary antiplatelet agent chosenaffect the outcome?

• Is short‐term, moderate‐term, or long‐termDAPT treatment the best in all situations?

Question 5Which of the following problems with bare‐metal coronary‐artery stents was addressed by the development of drug‐eluting stents?

Platelet aggregation and restenosis

Platelet aggregation and stent thrombosis

Neointimal hyperplasia and restenosis

Neointimal hyperplasia and stent thrombosis

Drug‐Eluting Stents• Elude: to avoid• Elute: to extract

Merriam‐Webster Online Dictionary. www.merriam‐webster.com (accessed 2015 Sept 22)

Stents after PCI: Why?• PCI is preferred for the management ACS

– Open artery hypothesis

• Balloon angioplasty (POBA) alone was used first– 40‐50% of patients experience restenosis at 6 months– 20‐30% require repeat procedure within 1 year

• Along come stents

Cannon CR et al. Am J Cardiol 1999;84:170‐5

Brief History of Stents in PCI• 1970’s

– POBA• 1980’s

– Bare‐metal stents— Improvements over angioplasty alone

– Efficacy & safety– Surgical standby unnecessary

—Limitations – 1/3 of patients needed revascularization

» Restenosis developed secondary to stent‐induced neointimal hyperplasia

– Aspirin approved for use after MI (1985)– ISIS‐2 (1988)

Stefanini G, et al. N Engl J Med. 2013;368:254‐265Fuster V, et al. Circulation. 2011;123:768‐778



Landmark Trial: ISIS‐2• Randomized trial of IV streptokinase, oral

aspirin, both, or neither among 17,187 casesof suspected myocardial infarction

• Arms– Streptokinase 1.5 MU infusion– Enteric‐coated aspirin 160 mg daily for 1 month– Both active treatments– Neither active treatment

ISIS‐2. Lancet. 1988;2:349‐60

ISIS‐2• Results

– Aspirin alone produced an absolute risk reduction in vascular deaths of 2.4% (RRR = 23%) when compared to placebo over 15 months

—NNT = 42– Aspirin in combination with streptokinase provided an

absolute risk reduction in vascular deaths of 5.2% (RRR = 42%) when compared to placebo over 15 months

—NNT = 19– Provided evidence of the efficacy of aspirin

administered within 24 hours of MI presentation

ISIS‐2. Lancet. 1988;2:349‐60

Advantages of DES• Reduced rates of restenosis by 50 ‐ 70% when

compared with BMS• Overall rate of restenosis became < 5%• Markedly reduced the need for repeat PCI

procedures for in‐stent restenosis• Rapidly became the most common type of

stent implanted in the U.S.

Morice MC et al. N Engl J Med 2002; 346:1773‐80Stone GW et al. N Engl J Med 2002; 350:221‐31.

Question 6In comparing complications of DES with BMS, which of the following is true?

Greater acute stent thrombosis with DES

Greater late stent thrombosis with DES

All stent thrombosis higher with DES

All stent thrombosis lower with DES

Complications of DES• Stent thrombosis

– This is a complication of ALL stents– Is the most feared complication– Is the timing of thrombosis different?

• What are the concerns with stent thrombosis?• Can the risk be modified or minimized?

Kirtane AJ et al. Circulation 2011;124:1283‐87.

Stent Thrombosis: Why are we concerned?

• Present as MI– Usually STEMI

• Always requires emergent PCI formanagement

• 30‐day mortality: 10 – 25 %• Recurrence: 20% will have a second episode

within 2 years




Where did the DES/DAPT controversy start?

• 2006 “ESC Firestorm”• BASKET‐LATE: 746 patients BMS vs. DES• 12‐month follow‐up after d/c clopidogrel• 6 cardiac deaths in DES group vs. 0 in BMS group• 20 MI in DES group vs. 3 in BMS group

– 13 of the DES MI events were due to stent thrombosis

– Mean time to event from clopidogrel discontinuation—116 days

Pfisterer M et al. J Am Coll Cardiol 2006;48:2584‐91.

Duke Heart Center Evaluation• 3609 patients stented with BMS or DES

– And had at least 12 months of follow‐up

• DES group: differences in events noted basedon clopidogrel use after 6 months– Death/MI: 3.1% in clopidogrel users after 6

months vs. 7.2% in discontinuation group

• BMS group: no such differences observed

Eisenstein EL et al. JAMA 2007;297:159‐68.

FDA Circulatory System Devices Advisory Panel 2006

• Two‐day meeting to discuss and makerecommendations regarding issues related to stent thrombosis with DES

• Large panel consisting of:– FDA Circulatory Panel (Physicians)– Physician experts in the field of PCI and DES– FDA staff– Members of companies that make DES

http://www.fda.gov/AdvisoryCommittees /CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/

FDA Curculatory System Devices Advisory Panel 2006

• After two days, no concrete recommendationscould be made due to:– Lack of consistent long‐term follow‐up– Inconsistent definitions of stent‐thrombosis– Use of DES in both "approved" and "unapproved"

settings– Censorship of follow‐up data

• Panel suggests "a minimum duration of at least12 months of DAPT after DES in patients with lowbleeding risk"

http://www.fda.gov/AdvisoryCommittees /CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/

Stent Thrombosis (ST) defined by the Valve Academic Research Consortium (2007)

• Definite– Angiographic or pathological confirmation of partial or

total thrombotic occlusion within the per‐stent region andat least one of the following

— Acute ischemic symptoms— Ischemic electrocardiogram changes— Elevated cardiac biomarkers

• Probable– Any unexplained death within 30 days of stent placement– Any MI without angiographic confirmation of ST

• Possible– Any unexplained death beyond 30 days

Claessen B, et al. J Am Coll Cardiol. 2014;7:1081‐92

Stent Thrombosis• Classification by timing

– Acute (< 24 hours)– Subacute (24 hours to 30 days)– Late (31 days to 1 year)– Very Late (> 1 year)

• Presentation– Chest pain– ECG changes in the territory of the target vessel– Sudden death

Mauri L et al. N Engl J Med.2007; 356:1020‐9.



Factors associated with stent thrombosis

• Patient related:– Smoking– Diabetes– CKD– ACS presentation– Thrombocytosis– High post‐procedure

platelet reactivity– Surgical procedures– Premature d/c of DAPT


• Lesion‐based:– Diffuse CAD with long

stented segments– Small vessel disease– Bifurcation disease– Thrombus containing

lesions– Significant inflow or

outflow lesions proximal or distal to stented segment

Factors associated with stent thrombosis

• Stent‐related factors:– Poor stent expansion– Edge dissections with limited inflow or outflow– Delayed or absent endothelialization of stent struts– Hypersensitivity/Inflammatory/Thrombotic reactions

to DES polymers– Strut fractures– Late malapposition or aneurysm formation– Neoatherosclerosis within stent with new plaque

rupture


Question 7Which of the following is a characteristic of FDA‐approved 2nd generation drug‐eluting stents that differentiates them from 1st generation stents?

The use of sirolimus elution to improve endothelial coverage

A stainless‐steel platform with improved radial strength and conformability

Improved polymer coatings that biodegrade after drug elution, resulting in a stent surface similar to bare‐metal stents

Thinner struts that may reduce arterial injury and risk of restenosis

Components of Drug‐Eluting Stents• Platform

– Stainless steel– Cobalt‐chrome– Platinum‐chrome

• Polymer coating– Controlled release drug

carriers• Antiproliferative agent

– Highly lipophilic– Effects:

— Immunosuppressant— Antiproliferative

Stefanini G, et al. N Engl J Med. 2013;368:254‐265http://pictures.doccheck.com/de/photo/4729/drug‐eluting‐stent‐mit‐aufgeblasenem‐ballonkatheter/

DES: Polymer and Strut thickness

Reprinted from The Lancet, Vol. 386, Piccolo R, Giustino G, Mehran R, Windecker S, Stable coronary artery disease: revascularisation and invasive strategies, Pages 702‐13, Copyright 2015, with permission from Elsevier.

1st Generation Drug‐Eluting StentsBrand Name Antiproliferative Agent Platform Strut Thickness

Cypher Sirolimus Stainless steel 140 μm

Taxus Express Paclitaxel Stainless steel 132 μm

Taxus Liberté Paclitaxel Stainless steel 97 μm

Stefanini G, et al. N Engl J Med. 2013;368:254‐265

• All reduced the rate of revascularization when compared tobare‐metal stents

• All have been associated with increased risk of very late stent thrombosis when compared with bare‐metal stents

• Risk of death and MI similar to bare‐metal stents




Question 8Compared with everolimus‐eluting stents, currently available evidence demonstrates that Resolute zotarolimus‐eluting stents are associated with:

A lower risk of cardiac death, myocardial infarction, repeat revascularization, and stent thrombosis

A similar risk of cardiac death, myocardial infarction, repeat revascularization, and stent thrombosis

A higher risk of cardiac death, myocardial infarction, repeat revascularization, and stent thrombosis

A similar risk of cardiac death, myocardial infarction, and repeat revascularization, but a reduction in stent thrombosis

2nd Generation Drug‐Eluting StentsBrand Name Antiproliferative

AgentPlatform Strut Width

Xience Everolimus Cobalt‐chrome 81 μm

Promus Everolimus Cobalt‐chrome 81 μm

Promus Element Everolimus Platinum‐chrome 81 μm


• In trials versus paclitaxel‐eluting stents– Reduced repeat revascularization, MI, and stent thrombosis

• In trials versus sirolimus‐eluting stents– Similar rates of death, MI, and repeat revascularization – Lower rates of stent thrombosis

2nd Generation Drug‐Eluting StentsBrand Name Antiproliferative

AgentPlatform Strut Width

Endeavor Zotarolimus Cobalt‐chrome 91 μm

Resolute Zotarolimus Cobalt‐chrome 91 μm


• In trials versus paclitaxel‐eluting stents– Similar rates of repeat revascularization – Reduced rates of MI

• In trials versus sirolimus‐eluting stents– Similar rates of stent thrombosis, death, and MI– Higher risk of repeat revascularization– Lower rate of very late stent thrombosis

Zotarolimus vs Everolimus Eluting StentsTrial Resolute All Comers Trial1 TWENTE Trial2

N 1140 1152 697 694

Antiproliferative agent Zotarolimus(Resolute)

Everolimus(Xience V)

Zotarolimus(Resolute)


Death (cardiac causes), any MI, revascularization of

target lesion at 12 months

8.2%P<0.001 for

noninferiority

8.3% 8.2%P<0.001 for

noninferiority

8.1%

360 day definite, probable,or possible stent thrombosis

2.3%P = 0.17

1.5% 1.4%P = 0.99

1.4%

DAPT upon discharge Aspirin ≥ 75 mg daily (indefinitely)

Clopidogrel 75 mg daily (≥ 6 months)

Aspirin 100 mg daily (indefinitely)

Clopidogrel 75 mg daily (12 months)

Trial Duration 13 months 12 months

1. Serruys P, et al. N Engl J Med. 2010;363;2:136‐1462. Birgelen C, el al. J Am Coll Cardiol. 2012;59:1350‐61

Antiplatelet Therapy:Does type of agent matter?

Does duration of therapy matter?

Question 9Which of the following medications was associated with a reduction in all‐cause mortality when given in combination with aspirin for the treatment of ACS?

Clopidogrel

Prasugrel

Ticagrelor

Ticlodipine




PLATO Study Design

Primary endpoint: CV death + MI + Stroke Primary safety endpoint: Total major bleeding

6–12‐month exposure

ClopidogrelIf pre‐treated, no additional loading dose;if naive, standard 300 mg loading dose,

then 75 mg daily maintenance;(additional 300 mg allowed pre PCI)

Ticagrelor180 mg loading dose, then90 mg bid maintenance;(additional 90 mg pre‐PCI)

NSTE‐ACS (moderate‐to‐high risk) or STEMI (if primary PCI)Clopidogrel‐treated or ‐naive;

randomised within 24 hours of index event (N=18,624)

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

PLATO Results: Primary and Secondary Endpoints

All patientsTicagrelor(n=9,333)

Clopidogrel(n=9,291)

HR for (95% CI) p value

Primary objective, n (%) CV death + MI + stroke 864 (9.8) 1,014 (11.7) 0.84 (0.77–0.92) <0.001

Secondary objectives, n (%)Total death + MI + stroke

CV death + MI + stroke +ischemia + TIA + arterial thrombotic events

Myocardial infarction

CV deathStroke

901 (10.2)

1,290 (14.6)

504 (5.8)353 (4.0)125 (1.5)

1,065 (12.3)

1,456 (16.7)

593 (6.9)442 (5.1)106 (1.3)

0.84 (0.77–0.92)

0.88 (0.81–0.95)

0.84 (0.75–0.95) 0.79 (0.69–0.91)1.17 (0.91–1.52)

<0.001

<0.001

0.0050.0010.22

All‐cause mortality 399 (4.5) 506 (5.9) 0.78 (0.69–0.89) <0.001


Total Major Bleeding

No Significant Differences

0

% per year

PLATO major bleeding

1

2

3

4

5

6

7

8

9

10

12

11

13

TIMI major bleeding

Red cell

transfusion*PLATO life‐threatening/fatal bleeding

Fatal bleeding

11.611.2

7.97.7

8.9 8.9

5.8 5.8

0.3 0.3

TicagrelorClopidogrel


Non‐CABG and CABG‐related Major Bleeding

p=0.026 p=0.025 p=NS p=NS

9

% per year

Non‐CABGPLATO majorbleeding

8

7

6

5

4

3

2

1

0Non‐CABG

TIMI major bleedingCABG

PLATO major bleeding

CABG TIMI major bleeding

4.5

3.8

2.8

2.2

7.4

7.9

5.3

5.8

TicagrelorClopidogrel


TRITON‐TIMI 38

Primary endpoint: CV death + MI + Stroke Primary safety endpoint: Total major bleeding

6–15‐month exposure

Clopidogrel300 mg loading dose then 75 mg daily maintenance

Prasugrel60 mg loading dose then10 mg daily maintenance

UA/NSTEMI (moderate‐to‐high‐risk)or STEMI all with scheduled PCI

(N=13,608)

Wiviott S, et al. N Engl J Med. 2007; 357:2001‐15.

TRITON‐TIMI 38 Results: Primary and Secondary Endpoints

All patientsPrasugrel(n=6813)

Clopidogrel(n=6795)

HR for (95% CI) p value

Primary objective, n (%) CV death + MI + stroke 643 (9.9) 781 (12.1) 0.81 (0.73–0.90) <0.001

Secondary objectives, n (%)Total death + MI + stroke

CV death + MI + stroke +rehospitalization for ischemia

Myocardial infarction

CV deathStroke

692 (10.7)

797 (12.3)

475 (7.3)133 (2.1)61 (1.0)

822 (12.7)

938 (14.6)

620 (9.5)150 (2.4)60 (1.0)

0.83 (0.75‐0.92)

0.84 (0.76‐0.92)

0.76 (0.67–0.85) 0.89 (0.70‐1.12)1.02 (0.71‐1.45)

<0.001

<0.001

<0.001 0.310.93

All‐cause mortality 188 (3.0) 197 (3.2) 0.95 (0.78‐1.16) 0.64

Wiviott S, et al. N Engl J Med. 2007;357:2001‐15.



TRITON‐TIMI 38

0

50

100

150

200

250

MajorBleeding

(Non‐CABG)

FatalBleeding

Bleedingrequiring

PRBC

Majorbleeding(CABG)

Prasugrel 146 21 244 24Clopidogrel 111 5 182 6

No of patients

Bleeding End Points

P = 0.03

P = 0.002 P <0.001

Wiviott S, et al. N Engl J Med. 2007;357:2001‐15.

P <0.001 Secondary Prevention:Does antiplatelet potency

matter?

CHARISMAClinically evident (stable) CVD or multiple CV risk factors

(n = 15603)Clinically evident (stable) CVD or multiple CV risk factors

(n = 15603)

Primary endpoint: CV death + stroke + MIMedian follow‐up: 28 months

Primary endpoint: CV death + stroke + MIMedian follow‐up: 28 months

Clopidogrel 75 mg daily + aspirin 75‐162 mg daily

(n=7802)

Clopidogrel 75 mg daily + aspirin 75‐162 mg daily

(n=7802)

Placebo + aspirin 75‐162 mg daily

(n= 7801)

Placebo + aspirin 75‐162 mg daily

(n= 7801)

Bhatt D, et al. N Engl J Med. 2006;354:1706‐1717

CHARISMA ResultsTrial CHARISMA

N 7802 7801

Therapies Clopidogrel 75 mg +aspirin 75 – 162 mg daily

Aspirin 75 – 162 mg daily

CV death + stroke + MI 6.8%P = 0.22

7.3%

Severe bleeding 1.7%P = 0.09

1.3%

Moderate bleeding 2.1%P <0.001

1.3%

Bhatt D, et al. N Engl J Med. 2006;354:1706‐1717

TRILOGY ACS Background The proportion of ACS (UA/NSTEMI) patients

world‐wide who are managed medically withoutrevascularization (PCI or CABG) is 40‐60%

Medically managed ACS patients have a two‐foldincrease in ischemic events, but have been under‐represented in contemporary ACS trials

Prasugrel, a thienopyridine P2Y12 inhibitor, wasshown to improve outcomes compared withclopidogrel in ACS patients undergoing PCI in theTRITON TIMI‐38 trial, with an increase in majorbleeding

Roe MT el al. N Engl J Med 2012; 367:1297‐1309.

TRILOGY ACS Study Design


Medically Managed UA/NSTEMI Patients

Clopidogrel1

75 mg MD

Prasugrel1

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)

Clopidogrel1300 mg LD

+75 mg MD

Prasugrel130 mg LD

+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.

Median Time to Enrollment = 4.5 Days



Baseline CharacteristicsAge < 75 Years (N = 7243) Overall Population (N = 9326)

Prasugrel(N = 3620)

Clopidogrel(N = 3623)

Prasugrel(N = 4663)


Age—yr 62 (56–68) 62 (56–68) 66 (58–74) 66 (59–73)

Female sex—% 36.2 35.6 39.2 39.1

Body weight < 60 kg—% 13.1 12.8 15.2 14.9

Disease classification—%

NSTEMI 67.8 67.2 70.4 69.4

Unstable angina 32.2 32.8 29.6 30.6

Medical History—%

Diabetes mellitus 38.5 39.3 37.7 38.3

Current/recent smoking 23.3 23.6 19.7 20.2

Prior myocardial infarction 43.3 44.8 42.9 43.3

Prior PCI 27.0 29.1 25.6 26.7

Prior CABG 14.6 16.3 15.2 16.1

Baseline risk assessment

GRACE risk score 114 (101–128) 115 (102–128) 122 (105–140) 121 (106–138)

Creatinine clearance—mL/min 81 (63–104) 81 (63–102) 73 (54–97) 73 (54–96)

Angiography performed pre‐randomization—% 42.1 43.1 41.2 41.4


HR (95% CI) ≤ 1 Year:0.99 (0.84, 1.16)

HR (95% CI) > 1 Year:0.72 (0.54, 0.97)

Primary Efficacy Endpoint to 30 Months

Reprinted from Roe MT et al. N Engl J Med 2012; 367:1297‐1309. With permission from the Massachusetts Medical Society.

HR (95% CI):0.91 (0.79, 1.05)

P = 0.21

Interaction P = 0.07

TIMI Major Bleeding to 30 Months

HR (95% CI):1.31 (0.81, 2.11)

P = 0.27

Reprinted from Roe MT et al. N Engl J Med 2012; 367:1297‐1309. With permission from the Massachusetts Medical Society.

Trilogy ACS: Conclusions In ACS patients managed medically without revascularization,

prasugrel was not significantly different in efficacy from clopidogrel during 2.5 years of follow‐up among patients < 75 years of age

Further analyses of the primary endpoint yielded several important findings favoring prasugrel treatment• Trend for a time‐dependent benefit after 1 year• Fewer total recurrent ischemic events, particularly after 1

year No significant differences in major, life‐threatening, or fatal

bleeding with prasugrel vs. clopidogrelRoe MT el al. N Engl J Med 2012; 367:1297‐1309.

PEGASUS: Rationale• In patients with a 1 ‐ 3 year history of MI who

are taking only ASA– Does DAPT reduce the incidence of major adverse

cardiovascular events (MACE) during long term follow‐up?

PEGASUS: Trial Design

Bonaca MP et al. N Engl J Med 2015;372:1791‐1800

Stable patients with a history of MI 1 ‐ 3 years prior + ≥ 1 additional risk factor

n ‐ 21,162

Ticagrelor 90 mg po BID

Ticagrelor 60 mg po BID

Placebo

RANDOMIZED, DOUBLE‐BLIND

ALL PATIENTS RECEIVED ASA 75 ‐ 150 MG PO DAILY

Mean follow‐up: 33 months




PEGASUS: Enrollment• Inclusion Criteria

– Age ≥ 50 years‐old• Plus at least one of:

– Age ≥ 65 years‐old– Diabetes – 2nd MI (> 1 year ago)– Multivessel CAD– CLcr < 60 mL/min

• Able to tolerate ASA


• Exclusion Criteria:• Planned use of:

– P2Y12 inhibitor– Cilostazol, dipyridamole– Anticoagulation

• History of:– ICH, CNS tumor

• Vascular abnormality• Recent GI Bleeding• Risk for bradycardia• Dialysis or severe liver

disease

PEGASUS: Endpoints• Efficacy primary endpoint:

– CV death, MI, stroke

• Safety primary endpoint:– TIMI Major Bleeding

• Other safety endpoints evaluated:– ICH, fatal bleeding, adverse drug events


PEGASUS: Efficacy ResultsTicagrelor 90 mg BID

Ticagrelor60 mg BID

Placebo Ticagrelor 90 mg vs placebo

Ticagrelor 60 mg vs placebo

CV Death, MI, Stroke

7.85% 7.77% 9.04% HR: 0.85 (0.75‐0.96)(p=0.008)

HR:0.84 (0.74‐0.95)(p=0.004)

CV Death 2.94% 2.86% 3.39% HR: 0.87 (0.71‐1.06)(p=0.15)

HR: 0.83 (0.68‐1.01)(p=0.07)

MI 4.40% 4.53% 5.25% HR: 0.81 (0.69‐0.95)(p=0.01)

HR: 0.84 (0.72‐0.98)(p=0.03)

Stroke 1.61% 1.47% 1.94% HR: 0.82 (0.63‐1.070(p=0.14)

HR: 0.75 (0.57‐0.98)(p=0.03)


PEGASUS: Safety


Ticagrelor 90 mg BID

Ticagrelor60 mg BID

Placebo Ticagrelor 90 mg vs placebo

Ticagrelor 60 mg vs placebo

TIMI Major Bleeding

2.6% 2.3% 1.06% HR: 2.39 (1.96‐3.7)(p<0.001)

HR:2.32 (1.68‐3.21)(p<0.001)

TIMI Minor Bleeding

1.31% 1.18% 0.36% HR: 4.15(2.47‐7.00)(p<0.001)

HR: 3.31(1.94‐5.63)(p<0.001)

Transfusion 2.43% 2.09% 0.72% HR: 3.75(2.59‐5.42)(p<0.001)

HR: 3.08(2.12‐4.48)(p<0.001)

Fatal Bleeding or non fatal ICH

0.63% 0.71% 0.60% HR: 1.22(0.74‐2.01)(p=0.43)

HR: 1.33(0.73‐1.97)(p=0.47)

PEGASUS: Conclusions• Adding Ticagrelor 60 mg BID to ASA in patients

with history of MI (1‐3 years ago)– Reduced recurrent MI – Reduced stroke– Increased major bleeding

—No increase in fatal events

• Long‐term DAPT could be considered inpatients with previous MI– Which patients?


Question 10Which of the following trials established that clopidogrel may be discontinued as early as 3‐months following implantation of a 2nd

generation drug‐eluting stent provided that aspirin is continued?

DAPT

ITALIC

PRODIGY

RESET



Studies Evaluating 3 vs. 12 months DAPT Trial RESET

N 1059 1058

Therapies Clopidogrel x 3 months + aspirin 100 mg indefinitely

Clopidogrel x 12 months + aspirin 100 mg indefinitely

CV death + MI + ST + TVR + bleeding

4.7%P <0.001

for noninferiority

4.7%

1st Gen. DES 0% 28.5%

2nd Gen. DES 100% 71.5%

Trial duration 12 months

Kim B, et al. J Am Coll Cardiol. 2012;60:1340‐8

ST = stent thrombosis; TVR = target vessel revascularization

Studies Evaluating 3 vs. 12 months DAPT Trial OPTIMIZE

N 1563 1556

Therapies Clopidogrel x 3 months + aspirin 100 mg indefinitely

Clopidogrel x 12 months + aspirin 100 mg indefinitely

Death+ MI + stroke + major bleeding

6.0%P = 0.002

for noninferiority

5.8%

1st Gen. DES 0% 0%

2nd Gen. DES 100% 100%


Feres F, et al. JAMA. 2013;310:2510‐2522

Studies Evaluating 6 vs. 12 months DAPT Trial EXCELLENT SECURITY ITALIC ISAR‐SAFE

N 1443 1399 1822 4000

Therapies Aspirin + clopidogrel

Aspirin + clopidogrel

(97%)


(98%)


Primary Endpoint/Outcome

CV death + MI + TVR

noninferior

CV death + MI + stroke + bleeding

noninferior

Death + MI + TVR + stroke +

bleedingnoninferior

Death + MI + stroke + bleeding

noninferior

1st Gen. DES 25% 0% 0% 10%

2nd Gen. DES 75% 100% 100% 72%

Trial duration 12 months 24 months 12 months 12 months

Gwon H, et al. Circulation. 2012;125:505‐513Colombo A, et al. J Am Coll Cardiol. 2014;64:2086‐97

Gilard M, et al. J Am Coll Cardiol. 2015;65:777‐86 Schultz‐Schupke S, et al. Eur Heart J. 2015;36:1252‐63

Studies Evaluating Prolonged DAPT(Beyond 12 months)

PRODIGYTrial PRODIGY

N 983 987

Therapies Clopidogrel x 6 months + aspirin 80 ‐ 160 mg

indefinitely

Clopidogrel x 24 months + aspirin 80 ‐ 160 mg

indefinitely

Death+ MI + stroke at 24 months post PCI

10%P = 0.91

10.1%

BMS 25% 25%

1st Gen. DES 25% 25%

2nd Gen. DES 50% 50%


Valgimigli M, et al. Circulation. 2012;125:2015‐2026

LATE TrialsTrial DES LATE1 REAL‐LATE2

N 2531 2514 1357 1344

Therapies DAPT Aspirin 100-200mg/day

DAPT Aspirin 100-200mg/day

MI or Death from (cardiac

causes)

2.6%P = 0.75

2.4% 1.8%P = 0.17

1.2%

Major Bleeding 1.4%P = 0.20

1.1% 0.2P = 0.35

0.1


All patients received at least 12 months of DAPT prior to randomization

1. Lee C, et al. Circulation. 2014; 129:304‐12.2. Park S, et al. N Engl J Med 2010; 362:1374‐82.



Question 11Which of the following represents the outcomes associated with DAPT therapy for 30 months vs. 12 months?

Reduced stent thrombosis but increased severe bleeding

Reduced MI and stent thrombosis but increased moderate bleeding

Reduced MI but increased severe bleeding

Reduced CV death but increased moderate bleeding

Dual antiplatelet therapy (DAPT) Study

Mauri L et al. N Engl J Med 2014;371:2155‐66

• Objectives:– In patients with DES: whether DAPT beyond 12

months is associated with: —reduction in stent thrombosis and/or —major adverse cardiovascular and cerebrovascular

events (MACCE)– Defined as a composite of: Death, MI, stroke

– To determine the impact of prolonged DAPT onmoderate or severe bleeding

DAPT Study Design

12 Month observational period: Open label ASA +

Thienopyridine(n: 25,682)

3‐Month observational

period: On ASA, off

Thienopyridine

THIENOPYRIDINE + ASPIRIN(n: 5020)

PLACEBO + ASPIRIN(n: 4941)

0 12 30 33Time in months after index stent procedure

Mauri L et al. N Engl J Med 2014;371:2155‐66.

Thienopyridine: Clopidogrel (65%), Prasugrel (35%) of patients enrolled

DAPT: Baseline characteristicsPatient Characteristics DAPT Continued

n=5020No DAPTn=4941

Age ‐ years 61.8 ±10.2 61.6 ±10.1

Female sex ‐ n (%) 1242 (24.7) 1284 (26)

Weight ‐ kg 91.5 ± 19.7 91.5 ± 19.4

Diabetes Mellitus(%) 31.1 30.1

Hypertension (%) 75.8 74

Smokers (%) 24.6 24.7

Stroke or TIA (%) 3.1 3.4

Prior myocardial infarction (%) 22 22.1

Reason for PCI: STEMI (%) 10.6 10.3

Reason for PCI: NSTEMI (%) 15.5 15.5

Reason for PCI: Unstable Angina (%) 16.7 16.7

Reason for PCI: Stable Angina (%) 37.5 37.8

Reason for PCI: other(%) 19.7 19.6Mauri L et al. N Engl J Med 2014;371:2155‐66

DAPT: DES type and drug therapy


Results: MACCE Endpoint




Results: Stent Thrombosis


Results: Myocardial Infarction


55% of these events wereNOT RELATED to stent

thrombosis

DAPT: Safety results


p=0.001P=0.004 p=0.15

Breakout Case # 1• MM is a 59‐year‐old man with a history of

CAD, Hypertension, type 2 Diabetes whopresents with NSTEMI

• Social history: (+) Smoking 2 packs per day• Taken to PCI:

– DES placed in proximal LAD– 70% occlusion in his RCA, which was left alone

during this procedure

Breakout Case # 1• Current medications (all oral):

– Aspirin 81 mg daily– Lisinopril 20 mg daily– Atorvastatin 80 mg daily– Amlodipine 5 mg daily– Metformin 1000 mg twice a day (currently

withholding)– Sitagliptin 100 mg daily

• Laboratory values are all within normal limits

Question 12For how long would you treat MM with DAPT?

1 month

6 months

12 months

Indefinitely



Breakout Case # 2• JG is a 73‐year‐old man who presents to his

cardiologist’s office for a 3‐month check‐upfollowing hospitalization for unstable angina

• Three months ago underwent PCI:– Endeavor stent placed in left circumflex artery

• PMH:– Prostate cancer (diagnosed 1 month ago)– CAD– Hyperlipidemia

Breakout Case # 2• Current medications:

– Leuprolide 7.5 mg sc once monthly– Bicalutamide 100 mg po daily– Pravastatin 40 mg po daily– Aspirin 81 mg po daily– Clopidogrel 75 mg po daily

Question 13For how long would you treat JG with DAPT?

3 months

6 months

12 months

Indefinitely

Key Takeaways• Key Takeaway #1

– The type of stent implanted will have a direct impact on duration of DAPT needed to prevent CV events

• Key Takeaway #2– The type of antiplatelet agent(s) chosen will also

impact patient outcomes• Key Takeaway #3

– At this time, there is not a “one size fits all” approach to the management of DAPT following DES implantation. Therapy should always be tailored to patient‐specific variables

Key Takeaways • Key Takeaway # 4: Patients to consider prolonged

DAPT:– Current smokers, CKD, Diabetes– Long stented segment– Small vessel stent placement– Large number of stents placed, diffuse CAD– Important locations:

—Proximal LAD, Left‐main coronary artery– Stent procedural complications:

—Malapposition, strut fractures, poor flow– Stent type: 1st generation vs. 2nd generation

Key Takeaways• Key Takeaway # 5: Patients to consider shorter

courses of DAPT:– Nonadherence concerns– Cost concerns– Bleeding risk deemed too high:

—History of major bleeding, ICH– ? Cancer history– BMS placement– Patients who require chronic anticoagulation therapy

(Atrial Fibrillation)



ACC/AHA: Classification of Recommendations and Levels of Evidence

A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

*Data available from clinicaltrials or registries about the usefulness/ efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use.

†For compara ve effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.


DES: Polymer and Strut thickness

Reprinted from The Lancet, Vol. 386, Piccolo R, Giustino G, Mehran R, Windecker S, Stable coronary artery disease: revascularisation and invasive strategies, Pages 702‐13, Copyright 2015, with permission from Elsevier.

Zotarolimus vs Everolimus Eluting StentsTrial Resolute All Comers Trial1 TWENTE Trial2

N 1140 1152 697 694

Antiproliferative agent Zotarolimus(Resolute)


Zotarolimus(Resolute)


Death (cardiac causes), any MI, revascularization of

target lesion at 12 months

8.2%P<0.001 for noninferiority

8.3% 8.2%P<0.001 for noninferiority

8.1%

360 day definite, probable,or possible stent thrombosis

2.3%P = 0.17

1.5% 1.4%P = 0.99

1.4%

DAPT upon discharge Aspirin ≥ 75 mg daily (indefinitely)

Clopidogrel 75 mg daily (≥ 6 months)

Aspirin 100 mg daily (indefinitely)

Clopidogrel 75 mg daily (12 months)


1. Serruys P, et al. N Engl J Med. 2010;363;2:136‐1462. Birgelen C, el al. J Am Coll Cardiol. 2012;59:1350‐61

Baseline CharacteristicsAge < 75 Years (N = 7243) Overall Population (N = 9326)

Prasugrel(N = 3620)


Prasugrel(N = 4663)


Age—yr 62 (56–68) 62 (56–68) 66 (58–74) 66 (59–73)

Female sex—% 36.2 35.6 39.2 39.1

Body weight < 60 kg—% 13.1 12.8 15.2 14.9

Disease classification—%

NSTEMI 67.8 67.2 70.4 69.4

Unstable angina 32.2 32.8 29.6 30.6

Medical History—%

Diabetes mellitus 38.5 39.3 37.7 38.3

Current/recent smoking 23.3 23.6 19.7 20.2

Prior myocardial infarction 43.3 44.8 42.9 43.3

Prior PCI 27.0 29.1 25.6 26.7

Prior CABG 14.6 16.3 15.2 16.1

Baseline risk assessment

GRACE risk score 114 (101–128) 115 (102–128) 122 (105–140) 121 (106–138)

Creatinine clearance—mL/min 81 (63–104) 81 (63–102) 73 (54–97) 73 (54–96)

Angiography performed pre‐randomization—% 42.1 43.1 41.2 41.4


Answer Key:

1. C 2. D 3. A 4. D 5. C 6. B 7. D 8. B 9. C 10. D 11. B 12. Audience Polling Question 13. Audience Polling Question


© 2015 American Society of Health-System Pharmacists

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