optimal lenght of dapt in different clinical...

Dr Grégoire Rangé / CH Chartres / France

Optimal lenght of DAPT in different clinical scenarios

…After PCI with DES

… in the light of recent and ongoing studies

DAPT duration depend on the evolution of risk’s balance

along time

D 0 D 365 D ?

Stent thrombosis

Bleeding

= Switch DAPT to SAPT

Clinical and procedural factors associated with ischemic and bleeding risks

(ACC 2016)

Advanced age

Female sex

BMI <25

CKD

Diabetes

Oral anticoagulation

Anémia

History of prior bleeding

NSAID or steroid

Advanced age

ACS

Prior MI

Extensive CAD

Diabetes

CKD

Ischemic risk Hemorragic risk

ACS

Diabetes

LVEF < 40 %

1er génération DES

ISR

Bifurcation

Stent undersized or deployed

Small diameter or long Stent

Risque TIS

J Am Coll Cardiol. 2016;68(10):1082-1115. doi:10.1016/j.jacc.2016.03.513

2016 ACC/AHA Guideline Focused Update

on Duration of Dual Antiplatelet Therapy

in Patients With Coronary Artery Disease:

Stable angina

What we must do (guidelines)

6 months 2014 ESC Guidelines

J Am Coll Cardiol. 2016;68(10)

2016 ACC/AHA Guideline Focused Update on Duration of

Dual Antiplatelet Therapy in Patients With Coronary Artery Disease

2016 ACC/AHA Guidelines

What we can do (published data)

3 months (meta-analysis; n =11473)

What we will do (ongoing study)

1 month and Ticagrelor alone ?

What we must do (Guidelines)

12 months

STEMI et NSTEMI (ESC NSTEMI 2015)

What we can do (published studies)

3 or 6 months

n % ACS Ischemic Bleeding

DES LATE, NEJM 2010 2117 60% 12 Mo = >12Mo No difference

EXCELLENT, JACC 2012 1443 50% 6 Mo = 12Mo No Difference

PRODIGY, Circulation 2012 2013 75% 6 Mo = 24 Mo More bleeding

RESET, JACC 2012 2117 55% 3 Mo = 12 Mo No difference

OPTIMIZE, JAMA 2013 3119 30% 3 Mo = 12 Mo More bleeding

ISAR SAFE, AHA 2014 4005 40% 6Mo = 12 Mo More Bleeding

Randomized studies S-DAPT vs L-DAPT

What we will do (on going study)

DAPT 3 months / Ticagrelor alone

TWILIGHT STUDY

High risk patient undegoing PCI with DES

High ischemic risk population

Giustino et al. JACC 2016

Procedural factors

Ischemic Benefit of long-term DAPT according to the degree of PCI complexity

Bonaca MP. NEJM. 2015.

Clinical factors High ischemic risk post MI patients PEGASUS : DAPT 12 vs 33 months

* Age >65 yrs, diabetes, 2nd prior MI, multivessel CAD,

or chronic non-end stage renal dysfunction

30 months or forever ?

ACC Guideline DAPT > 1 year reasonable (IIb)

in low risk bleeding patient

2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease

High bleeding risk patient What we must do (Guideline)

3-6 months 2014 ESC Guidelines

2016 ACC/AHA Guideline

What we can do (published study)

1 month LEADER FREE

DES (Biomatrix) vs BMS with one month DAPT In high hemorragic risk population (age> 75 ans , OAC,..)

Urban , NEJM 2014

Need Help ?

Advanced age

Female sex

BMI <25

CKD

Diabete

Oral anticoagulation

Anémia

History of prior bleeding

NSAID or steroid

Advanced age

ACS

Prior MI

Extensive CAD

Diabetes

CKD

Ischemic risk Hemorragic risk

ACS

Diabete

LVEF < 40 %

1er génération DES

ISR

Bifurcation

Stent undersized or deployed

Small diameter or long Stent

Risque TIS

J Am Coll Cardiol. 2016;68(10):1082-1115. doi:10.1016/j.jacc.2016.03.513

2016 ACC/AHA Guideline Focused Update

on Duration of Dual Antiplatelet Therapy

in Patients With Coronary Artery Disease:

?

DAPT score

PARIS score

DAPT duration in real life From CRAC registry (2016)

93,8% 87,1%

50,2%

94,6%

85,4%

55,1%

93,8%

82,2%

54,6%

0,0%

10,0%

20,0%

30,0%

40,0%

50,0%

60,0%

70,0%

80,0%

90,0%

100,0%

> 1 mois > 6 mois > 1 an

STEMI ST- Stable

% p

atie

nts

so

us

DA

PT

Conclusions

• The choice of DAPT duration is complex depending on many factors including initial clinical status and need a personalized evaluation for each patient of ischemic and hemorragic risk

• DAPT and PARIS scores could help the decision of DAPT continuation after 12 months

• On going studies with short DAPT and rapid switch with Ticagrelor alone could soon change the paradigm

Specific population with AC

Back up slides

What we must do (Guidelines)

1 month triple therapy

What we can do (published study)

Clopidogrel + AVK 12 Months

All Deaths Bleeding

WOEST trial

Post PCI SAPT + AVK vs DAPT+ AVK

Gibson

What we will do (on going study)

Clopidogrel + Rivaroxaban 12 Months

Kaplan-Meier Estimates of First Occurrence of Clinically Significant Bleeding Events

TIM

I M

ajo

r,

TIM

I M

ino

r, o

r B

leed

ing

Re

qu

irin

g M

ed

ica

l A

tte

ntio

n (

%)

697

Days

593 555 521 461 426 329VKA + DAPT

No. at risk

VKA + DAPT

26.7%

Treatment-emergent period: period starting after the first study drug administration following randomization and ending 2 days after stop of study drug.

Clinically significant bleeding is the composite of TIMI major, TIMI minor, and BRMA.

Hazard ratios as compared to the VKA group are based on the (stratified, only for Overall, 2.5 mg BID/15 mg QD comparing VKA) Cox proportional hazards model.

Log-Rank P-values as compared to VKA group are based on the (stratified, only for Overall, 2.5 mg BID/15 mg QD comparing VKA) two-sided log rank test. Gibson et al. AHA 2016

VKA + DAPT

Riva + DAPT

18.0%

p<0.00018

HR = 0.63 (95% CI 0.50-0.80)

ARR = 8.7

NNT = 12

706

697

636

593600

555

579

521

543

461

509

426

409

329

Riva + DAPT

VKA + DAPT

VKA + DAPT

Riva + P2Y12

16.8%

p<0.000013

HR = 0.59 (95% CI 0.47-0.76)

ARR = 9.9

NNT = 11

696

697

628

593606

555

585

521

543

461

510

426

383

329

Riva + P2Y12

VKA + DAPT

Riva + P2Y12

VKA + DAPT

Riva + DAPT

Riva + P2Y12 v. VKA + DAPT

HR=0.59 (95% CI: 0.47-0.76)

p <0.000013

ARR=9.9

NNT=11

Riva + DAPT v. VKA + DAPT

HR=0.63 (95% CI: 0.50-0.80)

p <0.00018

ARR=8.7

NNT=12

696

706

697

628

636

593

606

600

555

585

579

521

543

543

461

510

509

426

383

409

329

Riva + P2Y12

Riva + DAPT

VKA + DAPT

Kaplan-Meier Estimates of First Occurrence of CV Death, MI or Stroke

Card

iov

ascu

lar D

eath

, M

yo

card

ial

Infa

rcti

on

, o

r S

tro

ke (

%)

Days

Riva + P2Y12

Riva + DAPT

VKA + DAPT

694

704

695

648

662

635

633

640

607

621

628

579

590

596

543

562

570

514

430

457

408

VKA + DAPT

Riva + DAPT

Riva + P2Y12

Riva + P2Y12 v. VKA + DAPT

HR=1.08 (95% CI: 0.69-1.68)

p=0.750

Riva + DAPT v. VKA + DAPT

HR=0.93 (95% CI: 0.59-1.48)

p=0.765

6.5%

5.6%

6.0%

Treatment-emergent period: period starting after the first study drug administration following randomization and ending 2 days after stop of study drug.

Composite of adverse CV events is composite of CV death, MI, and stroke.

Hazard ratios as compared to VKA group are based on the (stratified, only for the Overall, 2.5 mg BID/15 mg QD comparing VKA) Cox proportional hazards model.

Log-Rank P-values as compared to the VKA group are based on the (stratified, only for Overall, 2.5 mg BID/115 mg QD comparing VKA) two-sided log rank test.

6 Subjects were excluded from all efficacy analyses because of violations in Good Clinical Practice guidelines

No. at risk

Gibson et al. AHA 2016

PIONEER study (post PCI + NVAF)

AVK + DAPT vs RVX (10mg) + DAPT vs RVX (15 mg) + SAPT

Patients With Atrial Fibrillation Undergoing

Coronary Stent Placement: PIONEER AF-PCI

• Primary endpoint: TIMI major + minor + bleeding requiring medical attention

• Secondary endpoint: CV death, MI, and stroke (Ischemic, Hemorrhagic, or Uncertain Origin)

*Rivaroxaban dosed at 10 mg once daily in patients with CrCl of 30 to <50 mL/min.

†Alternative P2Y12 inhibitors: 10 mg once-daily prasugrel or 90 mg twice-daily ticagrelor.

‡Low-dose aspirin (75-100 mg/d). ∆ Open label VKA

2100

patients

with NVAF

Coronary

stenting

No prior

stroke/TIA,

GI bleeding,

Hb<10,

CrCl<30

R

A

N

D

O

M

I

Z

E

1,6, or 12 months

Rivaroxaban 15 mg qd*

Clopidogrel 75 mg qd†

Rivaroxaban 15mg QD

Aspirin 75-100 mg qd

Rivaroxaban 2.5 mg bid


Aspirin 75-100 mg qd‡

VKA∆(target INR 2.0-3.0)


VKA∆ (target INR 2.0-3.0)



≤72

hours

After

Sheath

removal

1,6, or 12 months

End of treatment 12 months

WOEST

Like

ATLAS

Like

Triple

Therapy

Gibson et al. AHA 2016

Pre randomization MD Choice

Pre randomization MD Choice

optimal lenght of dapt in different clinical...

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