Updated HANDOUT FOR FREE CME--2018...18 charisma 125 1903 162 1943 prodigy 63 732 69 733

Copyright 2018 Creative Educational Concepts

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Disclaimer


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Tracy Y. Wang, MD, MHS, MSc, FAHA, FACCAssociate Professor of Medicine in Cardiology

Duke UniversityDurham, NC

1) Examine recent clinical data and ACC/AHA guideline updates regarding the optimal use and duration of dual antiplatelet therapy (DAPT) in acute coronary syndromes (ACS).

2) Individualize the duration of DAPT following ACS or percutaneous coronary intervention (PCI) by examining patient specific factors to balance ischemic vs. bleeding risk of extended DAPT.

3) Explore strategies members of the interprofessional healthcare team can employ to improve adherence and long‐term persistence to antiplatelet therapies at discharge and beyond.

Learning Objectives


3

• 61 year old man with diabetes and hypertension

• Admitted with NSTE ACS

• Received drug‐eluting stent (DES) to mid LAD thrombotic lesion

• EF=45% after PCI

• Now ready for discharge

Case 1

What do you tell the patient about his post‐discharge DAPT?

Case 1


4

History of Dual Antiplatelet Therapy (DAPT) in Patients with Coronary Artery Disease

Adapted from Valgimigli M, et al. Eur Heart J. 2017.

II ASPIRINTICLODIPINE

PRASUGREL

TICAGRELOR

1996 2017

ISAR(1996)

STAR(1998)

MATTIS(1998)

FANTASTIC(1998)

DAPT Duration

CLASSIC(2000)

COMMIT(2005)

CLARITY(2005)

CURE(2001)

CREDO(2002)

CURRENTOASIS 7(2010)

PLATO(2009)

TRITON(2007)

CHARISMA(2006)

ACCOAST(2013)

GRAVITAS(2011)

RESET(2012) OPTIMIZE

(2013)

ATLANTIC(2014) ISAR

TRIPLE(2015)

PRAGUE‐18(2016)

ANTARCTIC(2016)

NIPPON(2016)OPTIDUAL

(2016)PEGASUS(2015)

ITALIC(2015)

ISAR SAFE(2015)

WOEST(2013)

DES‐LATE(2014)

REAL‐LATEZEST‐LATE(2010)

EXCELLENT(2012)

TRILOGYACS(2013)

DAPT(2014)

SECURITY(2014)

PRODIGY(2012)

I‐LOVE‐IT 2(2016)

IVUSXPL

(2016)

1m

6m

12m

36m

ARCTIC(2012)

CLOPIDOGREL

.

CURE Trial (NSTE‐ACS)Primary Endpoint at 30 days: CV Death/MI/Stroke

~20% RRR95% CI=0.67‐0.92

P=.003

Clopidogrel+ ASA

10 20 30

Placebo + ASA

Days of Follow‐Up0

0.01

0.02

0.03

0.04

0.05

0.06

Cumulative Hazard Rate

for (M

I/CVA/CV Death)

0.00

RRR=relative risk reduction

From N Engl J Med. Yusuf S, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST‐segment elevation. 345(7):494‐502. Copyright © 2001 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.


5

15

CV Death, M

or CVA(%

)

0

5

10

0 30 90 180 270 360 450

HR 0.81(0.73‐0.90)P<.001

Prasugrel

Clopidogrel

Days

12.1%(781)

9.9% (643)

NNT=46

• 1.3% reduction in definite/probable stent thrombosis

• 0.6% increase in TIMI major bleeding; 0.3% increase in fatal bleeding

TRITON (Prasugrel)Patients with STEMI or NSTE‐ACS Undergoing PCI

From N Engl J Med. Wiviott SD, et al; TRITON‐TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. 357(20):2001‐2015. Copyright © 2007 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

Days after Randomization

0 60 120 180 240 300 360

12

11

10

9

8

7

6

5

4

3

2

1

0

13

CV Death, M

I or CVA (%)

9.8%

11.7%

HR 0.84 (95% CI 0.77–0.92)

P<.001

Clopidogrel

Ticagrelor

• 0.7% reduction in definite/probable stent thrombosis• 1.4% reduction in mortality• No increase in overall bleeding; 0.7% increase in non‐CABG PLATO major bleeding

PLATO (Ticagrelor)ACS Treated with either PCI or Medical Therapy

From N Engl J Med. Wallentin L, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. 361(11):1045‐1057.Copyright © 2009 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.


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DAPT in Patients with Recent ACS

Levine GN, et al. Circulation. 2016.

0 mo

6mo

12 mo

Recent ACS (NSTE‐ACS or STEMI)

No high risk bleeding and no significant overt bleeding on DAPT

Medical Therapy Lytic (STEMI) PCI (BMS or DES)

Class I:After CABG resume P2Y12inhibitor to

complete 1y of DAPT

(clopidogrel, prasugrel, ticagrelor)

Class I:At least 12 mo(clopidogrel, ticagrelor)

Class I:At least 14

days and up to 12 mo

(clopidogrel)

Class I:At least 12 mo(clopidogrel, prasugrel, ticagrelor)

CABG

Class IIb:>12 momay be reasonable

Class IIb:DC after 6 mo

may be reasonable

High bleeding risk or overt

bleeding

• For ACS (NSTE and STEMI) in general, patients should be managed with dual antiplatelet therapy for at least 12 months1

• Considerations for our patient: • Which P2Y12 inhibitor?

• Aspirin Dose?

• What factors would lead to shorter or longer duration recommendations?

Guideline Recommendations for Duration of DAPT in ACS

1Levine GN, et al. Circulation. 2016.


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1.8

0.9 0.9

0.10.3

2.4

1.41.1

0.4 0.3

0

2

4

TIMI MajorBleeds

LifeThreatening

Nonfatal Fatal ICH

Balance Against Higher Bleeding Risk% Events

ARD 0.6%HR 1.32

Clopidogrel Prasugrel

ARD 0.5%HR 1.52

ARD 0.2% ARD 0%ARD 0.3%

P=.03

P=.01P=NS

P=.002 P=NS

Wiviott SD, et al. N Engl J Med. 2007.

Intracranial Hemorrhage in Patients with Prior Stroke/TIA

(N=518)

Clopidogrel 0 (0%) Prasugrel 6 (2.3%)

P=.02

Recommendations COR LOE

It is reasonable to choose ticagrelor over clopidogrel for maintenance P2Y12 treatment in ACS patients treated with an early invasive strategy and/or PCI.

IIa B‐R

It is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 treatment in ACS patients who undergo PCI who are not at high risk for bleeding complications.

IIa B‐R

In ACS patients managed with medical therapy alone (without revascularization or fibrinolytic therapy) treated with DAPT, it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy.

IIa B‐R

Prasugrel should not be administered to patients with a prior history of stroke or TIA.

III: Harm

B‐R

Higher Potency Antiplatelet Therapy



8

As both monotherapy and as part of DAPT:

• Aspirin <100 mg = less bleeding then higher doses

• Aspirin 75‐150 mg = comparable to higher doses in reduction of ischemic events

Aspirin Dosing in Patients Treated with DAPT

COR LOE Recommendation

I B‐NRIn patients treated with DAPT, a daily aspirin dose

of 81 mg (range 75 mg–100 mg) is recommended


61 year old man with diabetes and hypertension admitted with NSTE ACS, received drug‐eluting stent (DES) to mid LAD thrombotic lesion, EF=45% after PCI. Now ready for discharge.

What do you tell this patient about his post‐discharge DAPT?

• Aspirin 81 mg daily (life long‐for now) + P2Y12 inhibitor (for at least 12 months)

• Is the patient able to tolerate and afford a higher potency P2Y12inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg BID)?

• Prepare patient for at least 1‐year of DAPT – Discuss financial considerations and eliminate barriers to adherence

• Planned evaluation of additional bleeding risk factors and re‐evaluation after 12 months for on‐going need of DAPT

Case 1


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ACS Patients NOT Taking Evidence‐Based Therapy At 1‐Year

% of Patients NOT Taking Prescribed Therapies

Bagnall AJ, et al. Circ Cardiovasc Qual Outcomes. 2010.

13.3%

66.7%

25%

39.7%

17.8%

0

20

40

60

80

100

AspirinN=1569

ClopidogrelN=1554

Beta BlockerN=1566

ACEIN=1556

StatinN=1571

Mathews R, et al. Circ Cardiovasc Qual Outcomes. 2015.

• As early as 6 weeks after hospitalization for MI, ~30% of MI patients are suboptimallyadherent to prescribed cardiovascular medications

• One third of patients with low adherence reported missing doses of their antiplatelet therapy at least twice a week following PCI

Medication Adherence Remains Suboptimal Early After MI


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Early Discontinuation of Dual Antiplatelet Therapy Increases Mortality

0.7%

7.5%

0

1

2

3

4

5

6

7

8

Continued Discontinued

Spertus JA, et al. Circulation. 2006.

Mortality (%

) at 12 M

onths

Hazard Ratio: 9.0295% CI: 1.3‐60.6; P=.02

Delays in Filling Clopidogrel Prescription After Hospital Discharge

• 7,402 patients after MI and stent placement

• 1 in 6 patients failed to fill their prescription on the day of discharge

• Median delay: 3 days

Ho PM, et al. Circ Cardiovasc Qual Outcomes. 2010.

Incidence of Death or MI

7.90%

14.20%

0%

4%

8%

12%

16%

20%

Same Day Late or Never

2 fold increase in MI or Death


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• “Meds‐to‐Beds” Programs – mobile pharmacy services bring discharge medications to the patient’s bedside

•Allows team to identify financial barriers prior to discharge

• Prior authorization obtained prior to discharge to decrease delays in therapy

• Identify those that are underinsured or uninsured

• Involve patient assistant programs

• Increased opportunity for pharmacist counseling, identification of medication errors

•Ensures medications are in hand before departure

Discharge Prescription Services

h ps://acc.mediasite.com/mediasite/Play/9eb 44d0 042899cdfa0fa0f855aad1d.

Proportion of Patients with PDC >80% For Each Medication Prescribed at Discharge

Composite Medication Adherence

Beta‐Blocker ACEI/ARB StatinP2Y12

InhibitorAdjusted OR(95% CI)

P

Adherence at 90 days

≤1 week 69.3 65.0 64.7 65.3 Reference

1‐2 weeks 71.4 64.6 64.2 66.01.01

(0.96‐1.06).71

2‐6 weeks 69.7 65.5 64.3 65.41.00

(0.95‐1.05).87

>6 weeks 61.3 56.8 58.3 57.10.74

(0.70‐0.77)<.001

Adherence at 1 year

≤1 week 62.2 55.4 57.0 64.1 Reference

1‐2 weeks 63.1 55.6 56.6 65.31.01

(0.95‐1.07).77

2‐6 weeks 61.1 55.1 56.4 64.50.98

(0.93‐1.03).48

>6 weeks 56.0 49.5 51.2 57.70.78

(0.73‐0.83)<.001

Early Follow‐up Improves Adherence

Faridi K, et al. JAMA Cardiol. 2016.


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Brown MT, et al. Fam Pract Manag. 2013; McHorney CA. Curr Med Res Opinion. 2009..

•85% of physicians believe the majority of their patients are adherent

•85% of patients surveyed state that they would not tell their doctor that they were not planning on buying a medicine

Deciding DAPT Discharge Regimen May Be Less Than Half the Battle

Garavalia L, et al. Eur J Cardiovasc Nurs. 2011.

Patients who discontinued antiplatelet therapy:• Unaware they should be taking the drug • Didn’t know for how long• “I was just taking it because they were telling me to”

Patients who continued antiplatelet therapy:• Could explain the purpose and benefit• Knew the intended duration of therapy• “keeps the pipes open” … “so things won’t stick”

30 Days Following MI and DES Placement


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Deciding DAPT Duration

DAPT in Patients with Recent ACS


0 mo

6mo

12 mo

Recent ACS (NSTE‐ACS or STEMI)

No high risk bleeding and no significant overt bleeding on DAPT

Medical Therapy Lytic (STEMI) PCI (BMS or DES)

Class I:After CABG resume P2Y12inhibitor to

complete 1y of DAPT

(clopidogrel, prasugrel, ticagrelor)

Class I:At least 12 mo(clopidogrel, ticagrelor)

Class I:At least 14

days and up to 12 mo

(clopidogrel)

Class I:At least 12 mo(clopidogrel, prasugrel, ticagrelor)

CABG

Class IIb:>12 momay be reasonable

Class IIb:DC after 6 mo

may be reasonable

High bleeding risk or overt

bleeding


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• Consider stopping DAPT and continue with single antiplatelet therapy (SAPT), preferably with the P2Y12 inhibitor especially in case of upper GI bleeding.

• If bleeding persists despite treatment or treatment is not possible, consider stopping all antithrombotic medications.

• Once bleeding has ceased, re‐evaluate the need for DAPT or SAPT, preferably with the P2Y12 inhibitor especially in case of upper GI bleeding.

• If DAPT is re‐started, consider shortening DAPT duration or switching to less potent P2Y12 inhibitor (i.e. from ticagrelor/prasugrel to clopidogrel), especially if recurrent bleeding occurs.

SEVERE BLEEDINGAny bleeding requiring hospitalization, associated with a severe blood loss

(>5 g/dl HB) which is hemodynamically stable and not rapidly evolving

e.g., severe genitourinary, respiratoryor upper/lower gastrointestinal bleeding

Valgimigli M, et al. Eur Heart J. 2017.

Bleeding During Treatment with DAPT

2017 ESC Recommendations for Management of DAPT with Bleeding

PPI Therapy and DAPTRecommendations Based on Risk of GI Bleeding

Recommendation

PPI use for patients with history of prior GI bleeding who require DAPT

PPI use for patients with increased risk of GI bleeding (advanced age, concomitant use of warfarin, steroids, NSAIDs, H. pylori infection, etc.) who require DAPT

Routine use of a PPI is not recommended for patients at low risk of GI bleeding, who have much less potential to benefit from prophylactic therapy

Levine GN, et al. J Am Coll Cardiol. 2011.

COR LOE

I C

IIa C

III: No Benefit

C


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• 65 year‐old male returns to clinic for 1 year follow‐up after his STEMI (treated with DES to the proximal LCx ‐3 mm vessel).

•Over the last year he has not had any recurrent ischemic events.

• EF preserved, on BP meds for hypertension. No diabetes.

•He has taken ASA 81 mg and ticagrelor 90 mg BID for the past year without interruption.

• Bruises easily, nuisance when he nicks himself shaving, but no major bleeding.

Case 2

What would you like to do with his DAPT?

A. Discontinue both ASA 81 mg daily and ticagrelor 90 mg BID

B. Discontinue ASA 81 mg daily and continue ticagrelor 90 mg BID

C. Discontinue ticagrelor and continue ASA 81 mg

D. Continue both ASA 81 mg and ticagrelor 90 mg BID

E. Continue ASA 81 mg daily and decrease ticagrelor to 60 mg BID

F. Continue ASA 81 mg and switch ticagrelor to clopidogrel 75 mg daily

Case 2


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• In patients who have no new ischemic event nor bleeding at the 1 year post‐ACS follow‐up

•Clinical evaluation

•Validated Risk Scores (DAPT Score/PRECISE Score)

•Patient preference and discussion

•Has therapy created a financial barrier?

•Have elective procedures been delayed?

Who Should Get LONGER DAPT Durations?

•High‐risk features predicting stent thrombosis

What You Need To Consider?

Patient Stent

• Diabetes• LV dysfunction• Multivessel disease• Prior stent thrombosis• Renal insufficiency• Recent ACS

• Long stent length• Bifurcation stent• Stent w/in stent• L main or prox LAD stent• Stent underexpansion/malapposition• Persistent slow flow• Dissection• Brachytherapy

Iakovou I, et al. JAMA. 2005.


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Months from Randomization

Ticagrelor 60 mgHR 0.84 (95% CI 0.74–0.95)

P=.004

CV Death, M

I, or Stroke (%)

3 6 9 120 15 18 21 24 27 30 33 36

Ticagrelor 90 mgHR 0.85 (95% CI 0.75–0.96)

P=.008

Placebo (9.04%)

Ticagrelor 90 mg (7.85%)

Ticagrelor 60 mg (7.77%)

6

5

4

3

10

9

8

7

2

1

0

N=21162Median follow‐up 33 months

NNT=84

NNT=79

PEGASUS: 1‐3 years Post‐MI

From N Engl J Med. Bonaca MP, et al. Long‐term use of ticagrelor in patients with prior myocardial infarction. 372(19):1791‐1800. Copyright © 2015 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

PEGASUS‐TIMI 54: Bleeding

2.6

1.3 1.2

0.6 0.7 0.6 0.6 0.6 0.50.1 0.3 0.3

2.3

1.1

0.4

0

1

2

3

4

5

TIMIMajor

TIMIMinor

Fatal bleeding orICH

ICH Fatal Bleeding

3‐Year

KM EventRate(%) Ticagrelor 90 mg

Ticagrelor 60 mg

PlaceboP<.001

P<.001

P=NS P=NS P=NS

Ticag 90: HR 2.69 (1.96‐3.70)

Ticag 60: HR 2.32 (1.68‐3.21)

Bonaca MP, et al. N Engl J Med. 2015.

• Based on PEGASUS data ticagrelor 60 mg twice daily was approved for use after one year following ACS

• 60 mg twice daily was as effective as 90 mg twice daily and associated with less bleeding


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CHARISMA 125 1903 162 1943

PRODIGY 63 732 69 733

ARCTIC‐Int’n 3 156 4 167

DAPT 59 1805 108 1771

DES‐LATE 56 1512 66 1551

PEGASUS 980 14095 578 7067

TOTAL 1286 20203 987 13232

P=.001

0.77 (0.61‐0.98)

0.91 (0.65‐1.28)

0.79 (0.18‐3.51)

0.52 (0.38‐0.72)

0.85 (0.60‐1.21)

0.84 (0.76‐0.94)

Study Events Total Events Total

Extended Aspirin Risk RatioDAPT Alone (95% CI)

0.2 0.5 1 2Extended DAPT Better Aspirin Alone Better

0.78 (0.67‐0.90)

1.1% absolute reduction over mean 31 month DAPT Rx

CV Death/MI/Stroke with Prolonged DAPT

Republished with permission of Oxford University Press from Udell JA, et al. Long‐term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta‐analysis

of randomized trials. Eur Heart J. 37(4):390‐399. 2016. Permission conveyed through Copyright Clearance Center.

CHARISMA 45 1903 39 1943

PRODIGY 9 732 6 733

ARCTIC‐Int’n 2 156 0 167

DAPT 34 1805 14 1771

DES‐LATE 39 1512 31 1551

PEGASUS 242 13946 54 6996

TOTAL 371 20054 144 13161

P=.004

1.17 (0.76‐1.79)

1.50 (0.53‐4.20)

5.35 (0.26‐110.6)

2.38 (1.27‐4.43)

1.27 (0.79‐2.03)

2.50 (1.86‐3.36)

Study Events Total Events Total

0.5 1 2 5Extended DAPT Better Aspirin Alone Better

1.73 (1.19‐2.50)

0.8% absolute increase over mean 31 month DAPT Rx

Extended Aspirin Risk RatioDAPT Alone (95% CI)

Major Bleeding with Prolonged DAPT

Republished with permission of Oxford University Press from Udell JA, et al. Long‐term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta‐analysis

of randomized trials. Eur Heart J. 37(4):390‐399. 2016. Permission conveyed through Copyright Clearance Center.


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Risk Scores Validated for Dual Antiplatelet Therapy Duration Decision‐Making

PRECISE DAPT Score (www.precisedaptscore.com)

DAPT Score(www.daptstudy.org)

Time of use At the time of coronary stenting After 12 months

DAPT durationShort DAPT (3‐6 months) vsStandard/long DAPT (12‐24 months)

Standard DAPT (12 months) vsLong DAPT (30 months)

Calculation Age≥7565 to <75<65

Cigarette smokingDiabetes mellitusMI at presentationPrior PCI or MIPaclitaxel‐eluting stentStent diameter <3 mmCHF or LVEF <30%Vein graft stent

‐2 pt‐1 pt0 pt+1 pt+1 pt+1 pt+1 pt+1 pt+1 pt+2 pt+2 pt

Score range 0 to 100 points ‐2 to 10 points

DecisionScore ≥25 = Short DAPTScore <25 = Standard/long DAPT

Score ≥2 = Long DAPTScore <2 = Standard DAPT

Reference Costa F, et al. Lancet. 2017. Yeh RW, et al. JAMA. 2016.

Taken as a whole, trials of prolonged or extended

DAPT suggest:

•Prolonged DAPT benefit/risk ratio more favorable in those with prior MI (compared to stable ischemic heart disease [SIHD])

•≈1% to 3% absolute decrease in ischemic events over the course of several years of Rx

•≈1% absolute increase in bleeding events over the course of several years of Rx

Prolonged or Extended DAPT >1 Year Post‐MI



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• 65 year old man returns for routine clinical follow‐up 1 year after his STEMI was treated with DES to the proximal LCx (3mm vessel) without complications.

• EF preserved, on BP meds for hypertension. No diabetes.

• He has taken ASA 81 mg daily and ticagrelor 90 mg BID for the past year without interruption. Bruises easily, nuisance when he nicks himself shaving, but no major bleeding.

What would you like to do with his DAPT?A. Discontinue ASA 81 mg daily and ticagrelor 90 mg BID

B. Discontinue ASA 81 mg daily, continue ticagrelor 90 mg BID

C. Discontinue ticagrelor, continue ASA 81 mg

D. Continue both ASA 81 mg and ticagrelor 90 mg BID

E. Continue ASA 81 mg daily and decrease ticagrelor to 60 mg BID

F. Continue ASA 81 mg and switch ticagrelor to clopidogrel 75 mg daily

Case 2 ‐ Continued

Dual Antiplatelet Therapy Study“DAPT Score”

Yeh RW, et al. JAMA. 2016.

Variable Points

Age ≥75 ‐2

Age 65 ‐ <75 ‐1

Age <65 0

Current cigarette smoker +1

Diabetes mellitus +1

MI at presentation +1

Stent diameter <3mm +1

Paclitaxel‐eluting stent +1

CHF or LVEF<30% +2

Saphenous vein graft PCI +2


21

Patients undergoing very late (>1 year) switch:

•De‐escalation (switching from prasugrel or ticagrelor to clopidogrel) should occur with a maintenance dose regimen (no loading dose).

•A lower dosing regimen of ticagrelor 60 mg BID has recently been approved by the FDA for post‐myocardial infarction patients >1 year from their index event.

•When ticagrelor therapy is initiated for post–myocardial infarction patients >1 year from their index event, a switch should be made directly to 60 mg BID maintenance dose (no loading dose) regardless of the prior P2Y12 inhibitor used.

2017 International Expert Consensus on Switching P2Y12 Inhibitors

Angiolillo DJ, et al. Circulation. 2017.

Switching P2Y12 Inhibitors: Expert Consensus

Adapted from Angiolillo DJ, et al. Circulation. 2017.

Acute/Early Phase (≤30 days)

Late/Very Late Phase (>30 days)

Clopidogrel

TicagrelorPrasugrel

Ticagrelor 180 mg LD(24 hours after last prasugrel dose)

Prasugrel 60 mg LD(24 hours after last ticagrelor dose)

Clopidogrel

TicagrelorPrasugrel

Ticagrelor 90 mg BID MD(24 hours after last prasugrel dose)

Prasugrel 60 mg LD(24 hours after last ticagrelor dose)

LD=loading doseMD=maintenance dose


22

•Two months after MI discharge, the patient returns for routine follow‐up. He completed cardiac rehab and still walks >1 mile daily. You elicit an irregular heart rhythm on exam, and ECG confirms presence of asymptomatic atrial fibrillation of unknown duration at a rate in the 70s. Heart rate in the 90s on metoprolol when ambulated in the clinic hallway. He has remained on ASA 81 mg and ticagrelor 90 mg BID since discharge without bleeding complications.

•What do you do next?

Case 3

What is your next step?

A. Schedule the patient for cardioversion to avoid the need for anticoagulation

B. Continue ASA and ticagrelor without change

C. Change ticagrelor to clopidogrel and add warfarin

D. Change ticagrelor to clopidogrel and add a DOAC

E. Continue ticagrelor and replace ASA with an anticoagulant

F. Change ticagrelor to clopidogrel and replace ASA with an anticoagulant

Case: Atrial Fibrillation and DAPT


23

• Assess ischemic and bleeding risks using validated risk predictors (CHA2DS2‐VASc and HAS‐BLED)

• Keep triple therapy durations as short as possible; dual therapy only (oral anticoagulant and clopidogrel) may be considered in select patients

• Clopidogrel is the P2Y12 inhibitor of choice

• Lessen intensity of anticoagulation: Consider target INR of 2.0‐2.5 when warfarin is used

• Use low dose (≤100 mg) aspirin

• Prophylactic proton‐pump inhibitors to reduce GI bleeding

ACC/AHA 2016 Triple Antithrombotic Treatment Consensus Recommendations


≤72hours

aftersheath removal

Pre‐Randomization Choice of Duration of DAPT & Thienopyridine: PIONEER AF‐PCI

RANDOMIZE

1 mo: 16%6 mos: 35%12 mos: 49%

Rivaroxaban 15 mg dailyClopi 95%, Ticag 4%, Prasugrel 1%

Rivaroxaban 15mg dailyAspirin 75‐100 mg daily

Warfarin(target INR 2.0‐3.0)

Aspirin 75‐100 mg dailyTTR 65%

Warfarin(target INR 2.0‐3.0)Clopi 95%, Ticag 4%,

Prasugrel 1%Aspirin 75‐100 mg QD

WOEST Like

ATLAS Like

TripleTherapy

1 mo: 16%6 mos: 35%12 mos: 49%

• 2100 patients with NVAF

• Coronary stenting

• No prior stroke/TIA, GI bleeding, Hb<10, CrCl<30

Gibson CM, et al. N Engl J Med. 2016.

Rivaroxaban 2.5mg BIDClopi 95%, Ticag 4%,

Prasugrel 1%Aspirin 75‐100 mg QD‡


24

5

Kaplan‐Meier Estimates of First Occurrence of Clinically Significant Bleeding Events: PIONEER AF‐PCI

TIMI M

ajor, TIM

I Minor, or Bleeding

Requiring Medical Attention (%)

Days

15

25

20

10

00 30 60 90 180 270 360

30

26.7%

18.0%

16.8%

Riva + P2Y12

Warfarin+ DAPT

Riva + DAPT

Riva + P2Y12 vs. Warfarin + DAPTHR=0.59 (95% CI: 0.47‐0.76)P<.000013ARR=9.9NNT=11

Riva + DAPT vs. Warfarin + DAPTHR=0.63 (95% CI: 0.50‐0.80)P<.00018ARR=8.7NNT=12

From N Engl J Med. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. Gibson CM, et al. 375(25):2423‐2434. Copyright © 2016 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

Kaplan‐Meier Estimates of First Occurrence of CV Death, MI or Stroke: PIONEER AF‐PCI

Cardiovascular Death, M

yocardial

Infarction, or Stroke (%)

Days

Warfarin + DAPT

Riva + DAPT

Riva + P2Y12

6.5%

5.6%6.0%

8

6

4

2

00 30 60 90 180 270 360

Riva + P2Y12 vs. Warfarin + DAPTHR=1.08 (95% CI: 0.69‐1.68)P=.750

Riva + DAPT vs. Warfarin+ DAPTHR=0.93 (95% CI: 0.59‐1.48)P=.765

From N Engl J Med. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. Gibson CM, et al. 375(25):2423‐2434. Copyright © 2016 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.


25

Dabigatran 110 mg dual therapy (n=981)

Warfarin triple therapy (n=981)

1.5

1

0.5

0

HR: 0.30 (95% CI: 0.08–1.07) P=0.064

Dabigatran 150 mg dual therapy (n=763)

Warfarin triple therapy (n=764)

HR: 0.12 (95% CI: 0.02–0.98) P=0.047

0.3%

1.0%

0.1%

1.0%

Patientswithoutcomeevent(%

)

ARR: 0.9%ARR: 0.7%

Cannon CP, et al. N Engl J Med. 2017.

RE‐DUAL PCI: Rate of Intracranial Hemorrhage

What is your next step?

A. Schedule the patient for cardioversion to avoid the need for anticoagulation

B. Continue ASA and ticagrelor without change

C. Change ticagrelor to clopidogrel and add warfarin

D. Change ticagrelor to clopidogrel and add a DOAC

E. Continue ticagrelor and replace ASA with an anticoagulant

F. Change ticagrelor to clopidogrel and replace ASA with an anticoagulant

Case: Atrial Fibrillation and DAPT


26

•Decisions about treatment and duration of DAPT require a thoughtful assessment of the benefit/risk ratio and consideration of patient preferences

•Shorter‐duration DAPT can be considered for patients at lower ischemic risk with high‐bleeding risk

• Longer‐duration DAPT may be reasonable for patients at higher ischemic risk with a lowering bleeding risk

• Lower doses of ASA are associated with less bleeding ‐> 81 mg daily is the recommended dose with DAPT

Take Home Lessons

• 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016.

Link: http://circ.ahajournals.org/content/134/10/e123.long

• 2017 ESC Focused Update on Dual Antiplatelet Therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J. 2017

Link: https://academic.oup.com/eurheartj/article ‐lookup/doi/10.1093/eurheartj/ehx419

• International Expert Consensus on Switching Platelet P2Y12 Receptor‐Inhibiting Therapies. Circulation. 2017.

Link: http://circ.ahajournals.org/content/136/20/1955.long

• Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A North American Perspective‐2016 Update. Circ Cardiovasc Interv. 2016.

Link: http://circinterventions.ahajournals.org/content/9/11/e004395.long

Resources


27

• American College of Cardiology (ACC). Surviving MI: an ACC quality initiative. Presented August 30, 2016. Author’s website. h ps://acc.mediasite.com/mediasite/Play/9eb 44d0 042899cdfa0fa0f855aad1d. Accessed June 2018.

• Angiolillo DJ, Rollini F, Storey RF, et al. International Expert Consensus on Switching Platelet P2Y(12) Receptor‐Inhibiting Therapies. Circulation. 2017;136(20):1955–1975.

• Bagnall AJ, Yan AT, Yan RT, et al; Canadian Acute Coronary Syndromes Registry II Investigators. Optimal medical therapy for non‐ST‐segment‐elevation acute coronary syndromes: exploring why physicians do not prescribe evidence‐based treatment and why patients discontinue medications after discharge. Circ Cardiovasc Qual Outcomes. 2010;3(5):530‐537.

• Bonaca MP, Bhatt DL, Cohen M, et al. Long‐term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372(19):1791–1800.

• Brown M, Sinsky CA. Medication adherence: we didn't ask and they didn't tell. Fam Pract Manag. 2013;20(2):25–30.

• Cannon CP, Bhatt DL, Oldgren J, et al; RE‐DUAL PCI Steering Committee and Investigators. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017;377(16):1513–1524.

• Costa F, van Klaveren D, James S, et al; PRECISE‐DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE‐DAPT) score: a pooled analysis of individual‐patient datasets from clinical trials. Lancet. 2017;389(10073):1025–1034.

• Faridi KF, Peterson ED, McCoy LA, et al. Timing of First Postdischarge Follow‐up and Medication Adherence After Acute Myocardial Infarction. JAMA Cardiol. 2016;1(2):147–155.

• Garavalia L, Ho PM, Garavalia B, et al. Clinician‐patient discord: exploring differences in perspectives for discontinuing clopidogrel. Eur J Cardiovasc Nurs. 2011;10(1):50–55.

• Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375(25):2423–2434.

• Ho PM, Tsai TT, Maddox TM, et al. Delays in filling clopidogrel prescription after hospital discharge and adverse outcomes after drug‐eluting stent implantation: implications for transitions of care. Circ Cardiovasc Qual Outcomes. 2010;3(3):261–266.

• Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug‐eluting stents. JAMA. 2005;293(17):2126–2130.

• Levine GN, Bates ER, Blankenship JC, et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44–e122.

References

• Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline forCoronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of PatientsWith Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST‐Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non‐ST‐Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016.

• Mathews R, Peterson ED, Honeycutt E, et al. Early Medication Nonadherence After Acute Myocardial Infarction: Insights into Actionable Opportunities From the TReatment with ADP receptor iNhibitorS: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE‐ACS) Study. Circ Cardiovasc Qual Outcomes. 2015;8(4):347–356.

• McHorney CA. The Adherence Estimator: a brief, proximal screener for patient propensity to adhere to prescription medications for chronic disease. Curr Med Res Opin. 2009;25(1):215–238.

• Spertus JA, Kettelkamp R, Vance C, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug‐eluting stent placement: results from the PREMIER registry. Circulation. 2006;113(24):2803–2809.

• Udell JA, Bonaca MP, Collet JP, et al. Long‐term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta‐analysis of randomized trials. Eur Heart J. 2016;37(4):390–399.

• Valgimigli M, Bueno H, Byrne RA, et al; ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National CardiacSocieties. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio‐Thoracic Surgery (EACTS). Eur Heart J. 2017 Aug 26. doi:0.1093/eurheartj/ehx419. [Epub ahead of print].

• Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–1057.

• Wiviott SD, Braunwald E, McCabe CH, et al; TRITON‐TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–2015.

• Yeh RW, Secemsky EA, Kereiakes DJ, et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315(16):1735–1749.

• Yusuf S, Zhao F, Mehta SR, et al. effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST‐segment elevation. N Engl J Med. 2001;345(7):494–502.

References

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