duration of dapt after pci in stable cad › static_file › escardio... · dapt (des) 9,961 30.6...

Duration of DAPT After PCI in Stable CAD

Prof. Dr. Helmut Schühlen, FESC, FACC

Vivantes Auguste-Viktoria-Klinikum

Berlin, Germany

Conflict of Interest Statement


Research support, speaker‘s or consulting honoraria from:

Astra Zeneca Abbott

Bayer Biotronik

Boehringer Ingelheim Bristol Myers-Squibb

Correvio Daiichi-Sankyo

Lilly Novartis

Pivotal Trials Establishing DAPT After BMS- DAPT Mandated for 4 Weeks - Event Rates at 30 Days -


0.7 0,5

5,4

2,72.9

0

1

2

3

4

5

6

ISAR STARSS

ten

t th

rom

bo

sis

(%)

n = 517 n = 1652

p < 0.005p = 0.004

aspirin +

ticlopidineaspirin + coumadin(+ overlapping heparin)

aspirin

monotherapy

A Schömig et al., N Engl J Med 1996 M Leon et al., N Engl J Med 1998

Incidence of Adverse Cardiac Events in Pivotal Early DAPT Trials


ISAR STARS

DAPT (aspirin + ticlopidine) aspirin + anticoagulation

A Schömig et al., N Engl J Med 1996 M Leon et al., N Engl J Med 1998

5,4

0,7

1,6

0,00

2

4

6

8

10

week 1+2 week 3+4

%

2,7

0,00,5

0,00

2

4

6

8

10

week 1+2 week 3+4

%

Late Stent Thrombosis in the Era of BMS + DAPT with Ticlopidine


B Doyle et al., Circulation 2007

Analysis of 4503 patients with aspirin + ticlopidinefor 4 wks.

30-day SAT rate:

0.5%

Early & Late Stent Thrombosis of BMSWith a 4-Week DAPT


Stent Thrombosis (%)Registry of18,334 pts

with BMS or DES

246 definite SAT

T Tada et al., JACC Intv 2013

years

0

0.5

1.0

2.0

3.0

0 1 2 3

1.5

2.5

BMS

1 month

Summary of First Part


After DAPT became standard after BMS placement, the optimal duration was never tested comprehensively.

Current data suggest that 4 weeks of DAPT after BMS might have been too short (and still may be).

DAPT Duration in Pivotal Trials of 1G-DES


RAVEL 8 wks.SIRIUS 3 mo.E- & C-SIRIUS 2 mo.

TAXUS I, II, IV-VI 6 mo.

Cypher ®

sirolimus-eluting, permanent polymer

Taxus ®

paclitaxel-eluting, permanent polymer

The Debate at ESC 2006


Mechanistic Insights into the Excess Risk ofLate Stent Thrombosis After 1G DES


AquiredMalapposition

Incomplete Endothelializationand Chronic Inflammation

Guagliumi et al., JACC Interv 2012

Guagliumi et al, Circulation 2003

18 mo. after implantation

Continuous Risk for Stent Thrombosis with 1st Gen. DES


Stent Thrombosis (%)

Registry of18,334 pts

with BMS or DES

246 definite SAT


years

0

0.5

1.0

2.0

3.0

0 1 2 3

1.5

2.5

BMS

1st Gen. DES

Independent Predictors forStent Thrombosis with 1st Gen. DES


I Iakovou et al., JAMA 2005

2229 pts. with 1st gen. DESClopidogrel for >3 mo. (Cypher) or >6 mo. (Taxus)

* > 30 days, up to 9 mo.

* n=15.

n=14.

Lower Risk for Stent Thrombosiswith 2nd-Gen. DES


E Kedhi et al., Lancet 2010

COMPARE Trial: 1800 patients, 60% ACS

stent thrombosis

Xience

Taxus

RR 0.26 (95% CI 0.11-0.64)

Late Stent Thrombosis with BMS, 1st-Gen. & 2nd-Gen. DES


1st-G. DES

BMS

2nd-G. DES

Registry of18,334 pts

with BMS or DES

246 definite SAT


DAPT Interruption & Stent ThrombosisAfter 2nd Gen. DES (Xience V)


P Généreux et al., Circ Cardiovasc

Interv 2015

Pooled data from 3 randomized trials & 4 registries11219 patients with 2 yr FU after Xience V placement


Data for ENDEAVOR RESOLUTE Stent to obtain CE Mark for 1 Mo. DAPT (3/2013)

Data from the RESOLUTE trial program with 5003 patients

S Silber, TCT 2012


DES vs. BMS in Patients withHigh Bleeding Risk & DAPT for 1 Mo.

Stent Thrombosisdefinite or probable

Primary EPdeath, MI or TVR

BMS

DES (Endeavor)

Randomization to Endeavor or BMSSubgroup of 828 patients (~48% ACS) with ≥1 bleeding risk criterion

Bleeding Risk Criteria

age > 80 yrs indication for oral anticoagulation other pro-hemorrhagic medication

(steroids, NSAID) recent bleeding episode known anemia (<10 mg/dl)

S Ariotti et al.,JACC Intv 2016


Polymer-Free BIOFREEDOM DES

P Urban et al., TCT 2015

N Engl J Med 2015

2466 patients with clinical indication for PCI& 1 or more inclusion criteria (high bleeding risk)

BMS(n=1227)

BioFreedom(n=1239)

DAPT for 4 wks.new P2Y12 inhibitors ~6%

triple Rx ~33%

Primary Safety EP: cardiac death, MI or stent thrombosisPrimary Efficacy EP: clinically-driven TLR (both at 1 yr.)

Polymer-Free BIOFREEDOM DES

Primary Safety EPcardiac death, MI or stent thrombosis

Primary Efficacy EPclinically-driven TLR

P Urban et al., TCT 2015 & N Engl J Med 2015


Summary After Second Part




First-generation DES were limited by delayed and/orincomplete healing, with a continuous thrombotic risk.

Data for 2G DES suggest that DAPT for 3 mo. may be safe.

… and 1 mo. DAPT may be safe with “3G“ DES.

Dedicated Randomized Trials on DAPT Duration After DES


SECURITY

ISAR-SAFE

REAL/ZEST LATE

Randomized Trials on the Duration of DAPT


Trial or Subgroup Patients, n Diabetics, % ACS, % Newer DES, % Thienopyridines

DAPT up to 12 mo.

EXCELLENT 1,443 38.2 51.1 74.8 Clopi

ISAR SAFE 4,000 24.5 40.0 88.6 Clopi

OPTIMIZE 3,119 35.3 5.4 N/A Clopi

RESET 2,148 29.3 58.6 44.8 Clopi

SECURITY 1,399 30.9 38.4 100 Clopi

DAPT >12 mo.

ARCTIC-Interruption 1,259 33.5 N/R 63.0 Clopi, Prasu

DAPT (DES) 9,961 30.6 42.6 47.2 Clopi, Prasu, Tica

DES LATE (extended) 5,045 28.1 60.7 34.2 Clopi

ITALIC/ITALIC plus 1,850 38.0 23.4 100 Clopi, Prasu, Tica

PRODIGY 1,970 24.2 74.4 50.2 Clopi



Randomization at Time ofPotential DAPT Interruption

DAPT

ISAR-SAFE

ARCTIC interruption

REAL / ZEST LATE

DES LATE

ITALIC

Randomization at Time ofStent Placement

EXCELLENT

PRODIGY

OPTIMIZE

RESET

SECURITY


all have a composite primary endpointnone was powered for mortality

* Placebo-controlled & blinded, all others are open-label

Randomization at Time ofStent Placement

Randomization at Time ofPotential DAPT Interruption

DAPT*

ISAR-SAFE*

ARCTIC interruption

REAL / ZEST LATE

DES LATE

ITALIC

EXCELLENT

PRODIGY

OPTIMIZE

RESET

SECURITY


… it‘s Time for Metaanalyses !



Lancet June 2015

shorter versus longer DAPTn=31666)

definite or probable SAT

major bleeding

all-cause death

HR 2.04 (1.48-2.80)

HR 0.58 (0.47-0.72)

HR 0.82 (0.69-0.98)

myocardial infarction HR 1.51 (1.28-1.77)

cardiac death HR 0.93 (0.73-1.17)

non-cardiac death HR 0.67 (0.51-0.89)


definite or probable SAT

major bleeding

all-cause death

myocardial infarction

cardiac death

Br Med J online 350:h1618

shorter DAPT

versus 12 mo.

n=15995)

OR 1.32 (0.83-2.08)

OR 0.58 (0.36-0.92)

OR 0.91 (0.71-1.18)

OR 1.11 (0.87-1.43)

OR 0.95 (0.68-1.33)

longer DAPT

versus 12 mo.

(n=16282)

OR 0.33 (0.21-0.51)

OR 1.62 (1.26-2.09)

OR 1.30 (1.02-1.66)

OR 0.53 (0.42-0.66)

OR 1.09 (0.79-1.50)


L Mauri et al., Eur Heart J 2016

DAPT Trial - Causes of Death

█ continued thienopyridine

█ placebo

ACS versus Non-ACS Patients


RW Yeh et al., ACC 2015 &

J Am Coll Cardiol 2015


DAPT Score

RW Yeh et al., AHA 2015

www.daptstudy.org


RW Yeh et al., J Am Coll Cardiol 2015

Does Prolonged DAPT MerelyDelay Stent Thrombosis ?

Post-Hoc Analysis

of theDAPT trial

after discontinuationof study drug

Final Summary




First-generation DES were limited by delayed and/orincomplete healing, with a continuous thrombotic risk.

Data for 2G DES suggest that DAPT for 3 mo. is safe.

… and 1 mo. DAPT may be safe with “3G“ DES.

Prolonging DAPT after 2G DES >6 mo. may decreaseischemic events, but increase bleeding & mortality.

duration of dapt after pci in stable cad › static_file › escardio... · dapt (des) 9,961 30.6...

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