DIRECT'ORAL'ANTICOAGUALANTS'(DOACS)' …sites.utexas.edu/phr-residencies/files/2018/09/...Sep 28, 2018 · Dual Therapy 150 mg HR 0.72 (95% CI 0.58-0.88) p=

!

!

!

A!Balancing!act!DIRECT'ORAL'ANTICOAGUALANTS'(DOACS)'

AND'ANTIPLATELET'THERAPY'IN'ATRIAL'

FIBRILLATION'PATIENTS'UNDERGOING'PCI''

'

September'28,'2018'

Pharmacotherapy'Rounds'

'

Olivia'Collado,'PharmD'

PGY1'Pharmacy'Resident'

Central'Texas'Veterans'Healthcare'System'

[email protected]'

' '

9/21/2018

1

A BALANCING ACT:DIRECT ORAL ANTICOAGULANTS (DOACS) AND ANTIPLATELET THERAPY IN ATRIAL FIBRILLATION PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION (PCI)Olivia M. Collado

PGY1 Pharmacy ResidentCentral Texas Veterans Healthcare System

September 28, 2018

Disclosures

• No conflicts of interest to disclose.

2

Objectives

1. Explain the challenge of balancing antiplatelet therapy and anticoagulant use in this patient population

2. Review available literature regarding dual and triple therapy with DOACs for antithrombotic strategies

3. Describe current guideline recommendations for specific regimens and duration

3

Patient case

• SH is a 66 yo M that presents with worsening chest pain during a fire drill at Dunder Mifflin Paper Company

• Transferred to emergency department with non-elevated troponin and admitted for NSTEMI and possible PCI

• PMH & Medications • Dyslipidemia: atorvastatin 40 mg daily• HTN (controlled): losartan 100 mg daily, amlodipine 5 mg daily• Diabetes: metformin 1000 mg twice daily, aspirin 81 mg daily • Atrial fibrillation: Dabigatran 150 mg twice daily

4

Patient case• Other pertinent information

⎯ Normal renal and liver function ⎯ No history of bleeding ⎯ No history of stroke/transient ischemic attack (TIA)⎯ Denies alcohol and tobacco use

5

Kahoot Question #1

• What is SH’s CHA2DS2VASc score ?

A. 1

B. 3

C. 2

D. 4

6

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2

Kahoot Question #2

• What is SH’s HAS-BLED score?

A. 1

B. 0

C. 2

D. 3

7

Patient case• SH is taken for cardiac catheterization

⎯ 80% stenosis in mid-LAD and stented with drug-eluting stent (DES)

• How do we manage his antithrombotic therapy?

⎯ Stent thrombosis prevention: antiplatelet therapy⎯ Atrial fibrillation (AF): oral anticoagulation

8

9

Background

9 10

Atrial Fibrillation

10

Atrial fibrillation

⎯ Most common heart arrhythmia

⎯ Affects ~ 7 million US, especially the elderly

⎯ Increase stroke risk by 4-5 X and mortality 2 X

11Andrade J, et al. Circ Res. 2014; 114 (9): 1453-1468.January CT, et al. Jour Am Coll Cardio. 2014; 64 (21): 2246-2280.

CHEST 2018 Guidelines

• Atrial fibrillation (Strong recommendations)

⎯ Oral anticoagulation• CHA2DS2VASc score > 1 male or > 2 female

⎯ HAS-BLED score

⎯ DOACs over vitamin K antagonist (VKA)

⎯ If VKA with time in therapeutic range (TTR) < 65%, switch to DOAC

12Gregory YH, et al. Chest. 2018; (18): 32244

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3

Kahoot Question #3

• What are some advantages of DOACs over warfarin for stroke prevention in non-valvular atrial fibrillation?

A. Standard dosing

B. No need for routine lab monitoring

C. Fewer drug interactions

D. All of the above

13

Chest 2018 Guidelines

14

Dabigatran Rivaroxaban Apixaban EdoxabanMechanism of action

Direct thrombin inhibitor

Factor Xa inhibitor

Factor Xa inhibitor

Factor Xa inhibitor

Approved dose for stroke prevention

150 mg twice daily75 mg twice daily

20 mg/d15 mg/d

5 mg twice daily2.5 mg twice daily

60 mg/d30 mg/d

Major bleedingStroke/SE Non-inferior

Gregory YH, et al. Chest. 2018; (18): 32244

150 mg 60 & 30 mg

150 mg 60 mg

15

Percutaneous coronary intervention (PCI)

15

Percutaneous coronary intervention

• Indicated for ACS or unstable angina

• Types of stents⎯ Bare-metal stents⎯ Drug-eluting stents

• Femoral and radial artery access• Complications

⎯ Stent thrombosis ⎯ Restenosis

16Bokhari S, et al. Cardiac catheterization. 2017

Kahoot Question #4

In general, what is appropriate DAPT therapy for ACS after PCI?

A. Aspirin 81 mg lifelong + warfarin; 12 mo

B. Aspirin 81 mg lifelong + clopidogrel 75 mg daily; 12 mo

C. Aspirin 81 mg lifelong + clopidogrel 75 mg daily; 6 mo

D. Aspirin 81 mg monotherapy lifelong; 6 mo

17

2016 ACC/AHA Dual antiplatelet therapy (DAPT) duration post-PCI

Levine GN, et al. 2016 ACC/AHA Guideline. J Am Coll Cardiol 2016; 68: 1082.

• ACS• Dual antiplatelet therapy after bare metal stent (BMS)/DES• Continue P2Y12 inhibitor for at least 12 mo (Class I)

• Clopidogrel• Prasugrel• Ticagrelor

• Low dose aspirin indefinitely• >12 mo if low bleed risk/ no bleed complication (Class IIb)

• Use DAPT score

18

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4

Antiplatelet agents

19

Aspirin Clopidogrel Prasugrel TicagrelorMOA Irreversible

inhibition of COX 1-2, PGs, TXA2

P2Y12 inhibitor

Dose 75-100 mg/d L: 600 mgM: 75 mg/d

L: 60 mgM: 10 mg/d

L: 180 mgM: 90 mg twice daily

2C19? Y* Y^ NInhibition Irreversible Irreversible Reversible Bleed + ++ ++*= sensitive to polymorphisms and drug interactions^= less sensitive to polymorphisms and drug interactionsCOX: Cyclooxygenase; PGs: prostaglandings; TXA2 : Thromboxane A2

Levine GN, et al. 2016 ACC/AHA Guideline. J Am Coll Cardiol 2016; 68: 1082. 20

AF & ACS Crossover

20

AF & ACS Crossover

21

ACS/Stenting

1-2 million people

Atrial Fibrillation~ 7 million

people

Stent + Afib20-30%

Lip GY, et al. Thromb Haemost. 2010; 103: 13-28.

A Balancing Act

22

Bleeding

Stent thrombosis & thromboembolic event prevention

Anticoagulation + Dual Antiplatelet

Conventional Standard-Triple Therapy

23Hansen MI, et al. Arch Intern Med 2010;170: 1433-1441.

Conventional Standard-Triple Therapy

24Hansen MI, et al. Arch Intern Med 2010;170: 1433-1441.

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5

25

Clinical QuestionAre there alternative treatment options other than triple therapy with warfarin for atrial fibrillation patients requiring oral anticoagulation undergoing PCI?

25 26

Trial Evidence

26

27

Trials

27

Dual and triple therapy with

warfarin

WOEST

ISAR-TRIPLE


DOACs

PIONEER AF-PCI

RE-DUAL PCI

28

Use of clopidogrel with or without aspirin in patients taking oral

anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomized, controlled trial

28

WOEST Trial (2013)

Intro Methods Results Conclusion

Dewilde W, et al. Am Heart J. 2009; 158 (5): 713-718.

29


• Inclusion criteria⎯ 18-80 yo, indication for OAC and PCI

• Treatment groups⎯ Triple therapy (TT): warfarin, clopidogrel, aspirin ⎯ Dual therapy (DT): warfarin, clopidogrel

• Primary endpoint⎯ Bleeding episode within 1 year of PCI

• Secondary endpoint⎯ Composite of death, myocardial infarction (MI), stroke,

target vessel revascularization (TVR), and stent thrombosis (ST)

Dewilde W, et al. Am Heart J. 2009; 158 (5): 713-718. 30

Primary Endpoint: Bleeding episode within 1 year of PCI


Secondary Endpoint: Composite of death, MI, stroke TVR, and ST

HR 0.36 (95% CI 0.26-0.60) p< .0001

HR 0.60 (95% CI 0.38-0.94) p=0.025

Dewilde W, et al. Am Heart J. 2009; 158 (5): 713-718.

9/21/2018

6

31

Authors’ Conclusion


• Compared to triple therapy with warfarin:

• Dual therapy with clopidogrel and OAC causes less bleeding

• Dual therapy with clopidogrel and OAC did not increase thrombotic events

Dewilde W, et al. Am Heart J. 2009; 158 (5): 713-718. 32

Trials


warfarin

WOEST

ISAR-TRIPLE


DOACs

PIONEER AF-PCI

RE-DUAL PCI

33

Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After

Drug-Eluting Stent Implantation

ISAR-TRIPLE (2015)


Fiedler KA, et al. J Am Coll Cardiol. 2015; 65 (16): 1619-1629. 34


• Inclusion criteria⎯ OAC at least 12 mo. and DES for ACS or stable angina

• Treatment groups⎯ 6 week clopidogrel or 6 mo. clopidogrel

• Primary endpoint⎯ Composite of death, MI, stroke, ST, Thrombolysis in

myocardial infarction (TIMI)-bleeding• Secondary endpoint

⎯ Composite of cardiac death, MI, ST, or ischemic stroke

Fiedler KA, et al. J Am Coll Cardiol. 2015; 65 (16): 1619-1629.

35

Primary Endpoint: Composite of death, MI, stroke, ST, TIMI-bleeding


Secondary Endpoint: Composite of cardiac death, MI, ST, or ischemic stroke

HR 1.14 (95% CI 0.68-1.91) p=0.63

HR 0.93 (95% CI 0.43-2.05) p=0.87

Fiedler KA, et al. J Am Coll Cardiol. 2015; 65 (16): 1619-1629. 36



• Six weeks of clopidogrel not superior to 6 months in patients taking concomitant aspirin and OAC

• Physicians should weigh the ischemic and bleed risk when choosing triple therapy duration

Fiedler KA, et al. J Am Coll Cardiol. 2015; 65 (16): 1619-1629.

9/21/2018

7

37

Trials


warfarin

WOEST

ISAR-TRIPLE


DOACs

PIONEER AF-PCI

RE-DUAL PCI

38

Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI

PIONEER AF-PCI (2016)


Gibson CM, et al. N Engl J Med. 2016; 375 (25): 2423-2434.

39


• Inclusion criteria⎯ > 18 yo with nonvalvular AF & undergone PCI with stent

• Treatment groups1. Rivaroxaban 15 mg/d + clopidogrel2. Rivaroxaban 2.5 mg/d + clopidogrel+asa3. Warfarin+clopidogrel+asa

• Primary endpoint⎯ Clinically significant bleeding

• Secondary endpoint⎯ Composite death from cardiovascular (CV) causes, MI, stroke

Gibson CM, et al. N Engl J Med. 2016; 375 (25): 2423-2434. 40

Primary Endpoint: Clinically significant bleeding


Secondary Endpoint: Composite of death from CV causes, MI, stroke

Group 1 vs 3 HR 0.59 (95% CI 0.47-0.76) p=<0.001

Group 2 vs 3 HR 0.63 (95% CI 0.50-0.80) p=<0.001

Group 1 vs 3 HR 1.08 (95% CI 0.69-1.68) p=0.75

Group 2 vs 3 HR 0.93 (95% CI 0.59-1.48) p=0.76


41



• Compared to triple therapy with warfarin,

• Both rivaroxaban treatment groups are associated with significant reduction in bleeding

• Both rivaroxaban treatment groups not associated with increased risk of MACE


PIONEER AF-PCI: Pros & Cons

42

Pros Cons• First to compare

DOAC regimen to triple therapy

• Open-label trial; small number of efficacy endpoints

• Lost 0 patients to follow-up

• Very-low-dose rivaroxaban

• Bleeding outcomes consistent across all criteria

• Little ethnic diversity

9/21/2018

8

43

Trials


warfarin

WOEST

ISAR-TRIPLE


DOACs

PIONEER AF-PCI

RE-DUAL PCI

44

Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation

RE-DUAL PCI (2017)


Cannon MD, et al. N Engl J Med. 2016; 375 (25): 2423-2434.

45


• Inclusion criteria⎯ > 18 yo with nonvalvular AF & undergone PCI with BMS or DES

• Treatment groups1. Dabigatran 110 mg twice daily + clopidogrel/ticagrelor2. Dabigatran 150 mg twice daily + clopidogrel/ticagrelor3. Warfarin+clopidogrel+asa

• Primary endpoint⎯ ISTH major or clinically relevant non-major bleeding event

• Secondary endpoint⎯ MACE

Cannon MD, et al. N Engl J Med. 2016; 375 (25): 2423-2434.46

Primary Endpoint: International society for thrombosis and hemostasis (ISTH) major or clinically relevant non-major bleeding event


Secondary Endpoint: Major adverse cardiac event (MACE)

Dual Therapy 110 mg HR 0.52 (95% CI 0.42-0.63) p=<0.001

Dual Therapy 150 mg HR 0.72 (95% CI 0.58-0.88) p=<0.002

Combined Dabigatran Dual TherapyHR 1.04 (95% CI 0.84-1.29) p=0.005 noninferiority


47



• Compared to triple therapy with warfarin,

• Dual therapy with dabigatran and a P2Y12inhibitor was associated with significantly lower risk of bleeding events

• Dual therapy with dabigatran and a P2Y12inhibitor was non-inferior regarding thromboembolic events


RE-DUAL PCI: Pros & Cons

48

Pros Cons• Both endpoints met

noninferiority • Open-label

• Study used standard dose for stroke prevention at 150 mg twice daily

• Small number of secondary efficacy endpoints

• Bleeding outcomes consistent across subgroups

• Long follow-up for VKA triple therapy

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9

Dual Therapy vs. Triple Therapy: Meta-Analysis

Overall Hazard Ratio (95% CI)

DAT arm TAT arm

TIMI major/minor bleeding

0.53 (0.36, 0.85) 130/3026 206/229

Stent thrombosis 1.00 (0.32, 2.82) 31/3024 21/2267Stroke 0.94 (0.45, 1.84) 39/3024 30/2267

Golwala HB, et al. Europ Heart Jour. 2018; 39: 1726-1735. 49

WOEST ISAR-TRIPLE

PIONEER AF-PCI

RE-DUAL PCI

Dual Therapy vs. Triple Therapy: Meta-Analysis

• Critique• Caution interpreting efficacy outcomes• Different baseline characteristics• Varying trial designs

• Conclusion

Dual therapy with OAC and a single antiplatelet may be a better option than triple therapy with warfarin and dual antiplatelet in many patients with atrial fibrillation following PCI.

Golwala HB, et al. Europ Heart Jour. 2018; 39: 1726-1735. 50

51

Future DOAC Dual Therapy Trials

DOAC Trials

52

Rivaroxaban(PIONEER AF-

PCI) 2015

Dabigatran(RE-DUAL PCI)

2016

Apixaban (AUGUSTUS) END 12/2018

53

A Study of Apixaban in Patients With Non-valvular Atrial Fibrillation With

High Thrombosis Risk Due to Having Had a Recent Coronary Event, Such as a

Heart Attack or a Procedure to Open the Vessels of the Heart

AUGUSTUS (ongoing)

AUGUSTUS (2018). Clinical Trials (Identification No. NCT02415400). 54

• Inclusion criteria⎯ AF (prior, persistent, >6 hr duration) with ACS and/or PCI with

planned P2Y12 inhibitor for 6 months ⎯ Physician decision that OAC is indicated

• Treatment groups1. Apixaban 5 mg twice daily with aspirin or placebo 2. Warfarin with aspirin or placebo

• Primary endpoint⎯ Major/clinically relevant bleeding (through 6 months)

• Secondary endpoint⎯ Death, MI, stroke, ST

ENTRUST-AF-PCI (2018). Clinical Trials (Identification No. NCT02866175).

AUGUSTUS, continued

9/21/2018

10

DOAC Trials

55

Rivaroxaban(PIONEER AF-PCI)

2015

Dabigatran(RE-DUAL

PCI) 2016

Apixaban (AUGUSTUS)

END 12/2018

Edoxaban(ENTRUST

AF-PCIEND 3/2019

56

Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial

Fibrillation Undergoing PCI

ENTRUST-AF-PCI (ongoing)


57

• Inclusion criteria⎯ OAC for AF X 12 mo. and PCI with stent placement

• Treatment groups1. Edoxaban 60 mg daily + P2Y12 antagonist 2. Warfarin + P2Y12 antagonist + asa 1-12 mo.

• Primary endpoint⎯ ISTH major and clinically relevant non-major bleeding


ENTRUST AF-PCI, continued

58

Current Guideline Recommendations

59

2018 Guideline Recommendations

EHRACHESTAHA

2018 AHA North American Consensus White PaperManagement of AF patients requiring OAC undergoing PCI

2018 Expert ConsensusChoice of anticoagulant

DOAC preferredIf VKA, INR 2-2.5OAC life-long

Choice of P2Y12inhibitor

Clopidogrel is the P2Y12 inhibitor of choice; ticagrelor if high ischemic/low bleed risk Prefer clopidogrel over aspirin

Strategy (double vs triple)

Dual therapy after hospital discharge Consider triple therapy X 1 mo if high ischemic/low bleed risk

Angiolillo DJ, et al. Circulation (2018). 60

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11

2018 AHA North American Consensus White PaperManagement of AF patients requiring OAC undergoing PCI

Angiolillo DJ, et al. Circulation (2018). 61 62


EHRACHESTAHA

2018 Updated CHEST Antithrombotic Guidelines

63

AF requiring OAC with ACS undergoing PCI Choice of anticoagulant

VKA TTR > 65-70% (INR 2-3) ORDOAC at stroke prevention dose Less bleeding with DOACs

Choice of P2Y12inhibitor

OAC with:• Low dose aspirin (ASA) + proton pump

inhibitor (PPI)• Clopidogrel preferred P2Y12 inhibitor


2018 Updated CHEST Antithrombotic Guidelines


Management of AF patients presenting with ACS requiring OAC undergoing PCI/stenting

(Weak Recommendations)

64

HAS-BLED 0-2 HAS-BLED >3Triple therapy X 6 mo. Triple therapy X 1-3 mo.

Dual therapy up to 12 mo. Dual therapy up to 12 mo.

OAC life-long OAC life-long

Triple therapy: OAC + aspirin/P2Y12-IDual therapy: OAC + P2Y12-I

65


EHRACHESTAHA

2018 Joint European Consensus

2018 Joint European Consensus. Europace. 2018. 66

9/21/2018

12

67

Key take home points

Key take home points, continued

• Dual therapy with a OAC + P2Y12-I preferred over triple therapy with warfarin in patients with AF + ACS

• Clopidogrel preferred • DOACs preferred over warfarin

• Rivaroxaban 15 mg once daily • Dabigatran 150 mg BID

68


69

1. Triple therapy with aspirin 81mg daily is used until hospital discharge. 2. For bleeding risk use HAS-BLED score: Low risk = 0-2, high risk = 3-4, very high risk >4.3. High atherothrombotic risk: For elective PCI use SYNTAX score; for ACS, GRACE score >140; stenting of the left

main, proximal LAD, proximal bifurcation; recurrent MIs; stent thrombosis etc. 4. DOAC is preferred over warfarin unless CI. Clopidogrel is preferred P2Y12 inhibitor; ticagrelor may be considered

in patients in at high thrombotic and low bleeding risk, avoid prasugrel.

Low Bleed Risk High Bleed Risk Very High Bleed RiskNormal Athero-thromboticRisk

• Triple therapy 1-3 mo. OR

• Dual therapy with OAC + P2Y12-I up to 12 mo.

• OAC lifelong

• Triple therapy 1 mo.• Dual therapy with OAC

+P2Y12-I up to 12 mo.• OAC lifelong


• OAC lifelong

High Athero-thromboticRisk

• Triple therapy 1-6 mo. • Dual therapy with OAC

+ P2Y12-I up to 12 mo. • OAC lifelong

• Triple therapy 1-3 mo.• Dual therapy with OAC

+ P2Y12-I up to 12 mo.• OAC lifelong



70

Patient Case Recap

Patient Case Recap, continued

71

AF+ NSTEMI

PCIDES Discharge

Kahoot Question #5• At discharge, what medication regimen is most appropriate

for SH, considering bleed and ischemic risk?

A. Warfarin (INR 2-3) + aspirin 81 mg + clopidogrel 75 mg daily; 1 mo

B. Rivaroxaban 20 mg daily + clopidogrel 75 mg daily ; 12 mo

C. Dabigatran 150 mg twice daily + aspirin 81 mg + clopidogrel 75 mg daily; 6 mo

72

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13


73

1. Triple therapy with aspirin 81mg daily is used until hospital discharge. 2. For bleeding risk use HAS-BLED score: Low risk = 0-2, high risk = 3-4, very high risk >4.3. High atherothrombotic risk: For elective PCI use SYNTAX score; for ACS, GRACE score >140; stenting of the left

main, proximal LAD, proximal bifurcation; recurrent MIs; stent thrombosis etc. 4. DOAC is preferred over warfarin unless CI. Clopidogrel is preferred P2Y12 inhibitor; ticagrelor may be considered

in patients in at high thrombotic and low bleeding risk, avoid prasugrel.

Low Bleed Risk High Bleed Risk Very High Bleed RiskNormal Athero-thromboticRisk

• Triple therapy 1-3 mo. OR


• OAC lifelong


+P2Y12-I up to 12 mo.• OAC lifelong


• OAC lifelong

High Athero-thromboticRisk

• Triple therapy 1-6 mo. • Dual therapy with OAC

+ P2Y12-I up to 12 mo. • OAC lifelong

• Triple therapy 1-3 mo.• Dual therapy with OAC




Acknowledgements

• Evaluator• Dr. Tamara Knight

• Preceptors

74

75

Questions?

Appendices!!!!

Appendix'A:'Figures'and'Tables'

Appendix'B:'Guideline'definitions'

Appendix'C:'Stroke'and'bleed'assessment'tools''

Appendix'D:'Abbreviations'

! !

Appendix!A.!Figures!and!Tables!

Slide'14:'Chest'2018'Guidelines'

'

!!

Slide'19:'Antiplatelet'agents'

!! !

Slide'23:'Conventional'StandardXTriple'Therapy'(Bleeding'outcomes)'

!

Slide'24:'Conventional'StandardXTriple'Therapy'(Ischemic'outcomes)'

'

'

'

Slide'60:'2018'AHA'North'American'Consensus'White'Paper'

'

Slide'61:'2018'AHA'North'American'Consensus'White'Paper'

'

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'

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'

Slide'63:'2018'Updated'CHEST'Antithrombotic'Guidelines'

!

Slide'64:'2018'Updated'CHEST'Antithrombotic'Guidelines'

'

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Slide'66:'2018'Joint'European'Consensus''

'

Slide'69:'Key'take'home'points''

!! !

Appendix!B.!Definitions!!'

Classification'of'atrial'fibrillation''

• Paroxysmal:'terminates'spontaneously'or'with'intervention'within'seven'days'of'onset.'

• Persistent:'fails'to'selfXterminate'within'7'days;'often'requiring'pharmacologic'or'electrical'

cardioversion'to'restore'sinus'rhythm.''

• Long0standing:'lasting'for'more'than'12'months.'

• Permanent:'persistent'AF'where'a'joint'decision'by'the'patient'and'clinician'has'been'made'to'no'

longer'pursue'a'rhythm'control'strategy.''

2018'Chest'guideline'definitions'

• Unusually4high4bleed4risk:'patients'with'HASXBLED'>'3'and'recent'acute'bleeding'event.'4• High4thrombotic4risk:'left'main'stent,'multiXvessel'PCI/stenting.'

Bleeding'criteria'definitions'

'

TIMI4criteria''

TIMI!Bleeding!Criteria!Major! ICH;'Hb'drop'>'5'g/d;''Hct'drop'>15%'

Minor! Bleeding;'Hb'drop'>'3'g/d;''Hct'drop'>10%'

No'observed'blood'loss:'Hb'drop'>'4'g/dL;'Hct'drop'>'12%'

Minimal! Any'clinically'overt'sign'of'hemorrhage'associated'with'Hb'drop'<3'g/dL'or'Hct'

drop'<9%'

'

BARC4bleeding4criteria4

BARC!Bleeding!Type!1! Not'actionable,'does'not'cause'unscheduled'studies,'hospitalization,'or'treatment;'may'

include'episodes'leading'to'selfXdiscontinuation'of'medical'therapy'

Type!2! Any'overt,'actionable'sign'of'hemorrhage'that'does'not'fit'the'criteria'for'types'3,4,'or'5'

but'does'meet'>'1'of'the'following'criteria:'(1)'requiring'nonsurgical,'medical'

intervention;'(2)'leading'to'hospitalization'or'increased'level'of'care;'or'(3)'prompting'

evaluation'

Type!3a! Overt'bleeding'+'Hb'drop'3X5'g/dL;'any'transfusion'with'overt'bleeding'

Type!3b! Overt'bleeding'+'Hb'drop'>5'g/dL;'cardiac'tamponade;'bleeding'requiring'surgical'

intervention'or'IV'vasoactive'agents''

Type!3c! ICH'(not'including'microbleeds'or'hemorrhagic'transformation,'does'include'intraspinal)''

Subcategories'confirmed'by'autopsy'or'imaging'or'lumbar'puncture''

Intraocular'bleed'compromising'vision''

Type!4! CABG'bleeding'

Type!5! Fatal'bleeding''

'

'

'

ISTH4

ISTH!Bleeding!Definitions!Major!Bleeding! Fall'in'Hgb'>'2'g/dl,'or'transfusion'of'>'2'units'of'PRBC'or'

whole'blood,'or'that'occurs'in'a'critical'location'i.e.'

intracranial,'or'that'causes'death'

Clinically!Relevant!NonIMajor!Bleeding! Does'not'meet'criteria'for'major'bleeding'that'requires'any'

medical'or'surgical'intervention'to'treat'the'bleeding'

'

GUSTO44

GUSTO!Bleeding!Severe! ICH;'bleeding'that'causes'hemodynamic'compromise'and'requires'intervention'

Moderate! Bleeding'requiring'transfusion'but'does'not'lead'to'hemodynamic'instability''

Mild! Bleeding'that'does'not'meet'criteria'for'severe'or'moderate'bleeding'

'

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'

Chesebro'JH,'et'al.'Circulation.'1987;'76:'142X154.''GUSTO'Investigators.'N4Engl4J4Med.'1993;'329:'673X682.''Mehran'R,'et'al.'Circulation.'2011;'123:'2736X2747.''Gregory'LH,'et'al.'Antithrombotic'Therapy'for'Atrial'Fibrillation:'CHEST'guideline'and'Expert'Panel'Report.'2018.'Chest4Journal.'! '

Appendix!C.!Ischemic!or!atherothrombotic!risk!and!bleed!assessment!tools!'

CHA2DS20VASc4score44

Congestive!heat!failure! !sign/symptoms+of+heart+failure+or+objective+evidence+of+reduce+left8ventricular+ejection+fraction++

+1!

Hypertension'Resting+blood+pressure+>+140/90+mmHg+on+at+least+2+occasions+or+current+antihypertensive+treatment++

+1'

Age'>75+

+2'

Diabetes!mellitus!Fasting+glucose+>126+mg/dL+or+treatment+with+oral+hypoglycemic+agent+and/or+insulin+

+1'

Previous!stroke,!transient!ischemic!attack,!or!thromboembolism+ +2'

Age!65I74' +1'

Sex!category!(female)' +1'

'

0='low'

1=lowXmoderate'

>2'='moderateXhigh'

HAS0BLED4

Hypertension!! !uncontrolled,+>160+mmHg+systolic+

+1!

Abnormal!liver!function'Cirrhosis+or+bilirubin+>+2+X+normal+with+AST/ALT/AP+>+3+X+normal+

+1'

Abnormal!renal!function'Dialysis,+transplant,+Cr+>+2.26+mg/dL+or+>+200+umol/L+

+1'

Stroke' +1'

Bleeding!prior+major+bleeding+or+predisposition+to+bleeding+

+1'

Labile!INR'Unstable/high+INR,+time+in+therapeutic+range+<+60%+

+1'

Elderly!>65' +1'

Drugs:!concomitant!antiplatelet!!aspirin,+clopidogrel,+NSAIDS+

+1'

Drugs:!concomitant!excess!alcohol!use!'>+8+drink/+week+

+1'

'

0X2'Lo'bleed'risk'

3X4'High'bleed'risk''

>4'Very'high'bleed'risk''

'

'

DAPT4score4Predicts'patients'that'will'benefit'from'prolonged'DAPT'after'coronary'stent'placement4

Age!>+75++65874+<65+

!I2!I1!0!

Cigarette!smoking+Smoking+within+2+year+prior+to+index+procedure+

+1'

Diabetes!mellitus' +1'

MI!at!presentation+ +1'

Prior!PCI!or!prior!MI+ +1'

PaclitaxelIeluting!stent+ +1'

Stent!diameter!<!3!mm' +1'

CHF!or!LVEF!<!30%' +2'

Vein!graft!stent' +2'

'

X2''''''X1''''''0''''''1''''''2''''''3''''''4''''''5''''''6''''''7''''''8''''''9''

Greater'' ' ' ' ' ' Greater'

Bleed'Risk' ' ' ' ' ' Thrombotic'Risk'

Syntax4Score4Algorithm44Score'complexity'of'CAD4

Dominance!!Number!of!lesions!Segments!involved!per!lesion,!with!lesion!characteristics!!Total!occlusions!with!subtotal!occlusions:'number'of'segments,'age'of'total'

occlusions,'blunt'stumps,'bridging'collaterals,'first'segment'beyond'occlusion'visible'

by'antegrade'or'retrograde'filling,'side'branch'involvement''

Trifurcation,!number!of!segments!diseased!Bifurcation!type!and!angulation!AortoIostial!lesion!Severe!tortuosity!Lesion!length!Heavy!calcification!Thrombus!Diffuse!disease,!with!number!of!segments!!'

4

4

4

4

4

GRACE4Score''Estimates'admissionX6'month'mortality'for'patients'with'acute'coronary'syndrome'4

Age! <40=0'

49X40=18'

59X50=36'

69X60=55'

79X70=73'

>'80='81!!Killip!class! I='0'

II=21'

III=43'

IV=64'

Systolic!blood!pressure! <80=63'

99X30=58'

119X100=47'

139X120=37'

159X140=26'

199X160=11'

>200=0'

Presence!of!ST!segment!deviation!! Yes=30'

Cardiac!arrest!during!presentation! Yes=43'

Serum!creatinine!concentration! 0.0X0.39=2'

0.4X0.79=5'

0.8X1.19=8'

1.2X1.59=11'

1.6X1.99=14'

0.2X3.99=23''

>'4='31'

Presence!of!elevated!serum!cardiac!biomarkers!

Yes=15'

Heart!rate!! <70=0'

89X70=7'

109X90=13'

149X110=23''

199X150=36'

>200=46''

'

'

'

!!!!!Kumar'K,'et'al.'Overview'of'atrial'fibrillation.'In:'Post'T,'ed.'UpToDate.'Waltham,'Mass.:'UpToDate;'2018.'!Assessment'tools.''American4College4of4Cardiology.'Accessed'9/10/18.''

Appendix!D.!Abbreviations!!

ACS:'acute'coronary'syndrome'

AF:'atrial'fibrillation'

BARC:'Bleeding'academic'research'consortium'

BP:'blood'pressure''

CAD:'coronary'artery'disease''

CHF:'congestive'heart'failure''

COX:'cyclooxygenase''

CRNM:'clinically'relevant'nonmajor'bleeding''

DAPT:'dual'antiplatelet'therapy''

DES:'drugXeluting'stent''

DOACs:'DirectXacting'oral'anticoagulants''

ESC:'European'Society'of'Cardiology''

HTN:'hypertension''

INR:'international'normalized'ratio''

ISTH:'International'society'for'thrombosis'and'hemostasis'

MACE:'major'adverse'cardiac'event''

MI:'myocardial'infarction''

NVAF:'nonvalvular'atrial'fibrillation''

OAC:'oral'anticoagulation''

PCI:'percutaneous'coronary'intervention''

PG:'prostaglandins'

PUD:'peptic'ulcer'disease''

SAPT:'single'antiplatelet'therapy''

SE:'systemic'embolism''

SIHD:'stable'ischemic'heart'disease'

TIA:'transient'ischemic'attack''

TIMI:'Thrombolysis'in'Myocardial'Infarction''

TT:'triple'therapy'

TTR:'time'in'therapeutic'range'

TXA2:'Thromboxane'A2'

VKA:'vitamin'K'antagonist''

'

Documents

DIRECT'ORAL'ANTICOAGUALANTS'(DOACS)' …sites.utexas.edu/phr-residencies/files/2018/09/...Sep 28, 2018 · Dual Therapy 150 mg HR 0.72 (95% CI 0.58-0.88) p=