Dual Antiplatelet Therapy (DAPT) Duration Dilemma: Recent Trials And Guidelines For Clinical Practice Dean J. Kereiakes, MD FACC FSCAI Medical Director, The Christ Hospital Heart & Vascular Center and the Lindner Research Center at The Christ Hospital, Cincinnati, Ohio Professor of Clinical Medicine, Ohio State University
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Dual Antiplatelet Therapy (DAPT) Duration Dilemma: Recent Trials And Guidelines For
Dual Antiplatelet Therapy (DAPT) Duration Dilemma: Recent Trials And Guidelines For Clinical Practice. Dean J. Kereiakes, MD FACC FSCAI Medical Director, The Christ Hospital Heart & Vascular Center and the Lindner Research Center at The Christ Hospital, Cincinnati, Ohio - PowerPoint PPT Presentation
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Dual Antiplatelet Therapy (DAPT) DurationDilemma: Recent Trials And Guidelines ForClinical Practice
Dean J. Kereiakes, MD FACC FSCAIMedical Director, The Christ Hospital Heart & Vascular Center and the Lindner Research Center at The Christ Hospital, Cincinnati, OhioProfessor of Clinical Medicine, Ohio State University
Solutions, Inc.• Significant: Boston Scientific, Abbott
Vascular, REVA Medical Inc.
3
2011 ACC/AHA/SCAI Guideline for PCIThe duration of P2Y12 inhibitor therapy should generally be as follows:
DURATION
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIa. In patients receiving a stent (BMS or DES)
during PCI for ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include clopidogrel 75 mg daily,prasugrel 10 mg daily or ticagrelor 90mg twice daily
b. In patients receiving DES for non-ACS indication, clopidogrel should be given for at least 12 months if patients are not at high risk for bleeding.
c. In patients receiving BMS for a non-ACS indication, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless patient is at increased risk for bleeding;then it should be given for a minimum of 2 weeks) Circulation 2011;124:e574-651
Primary endpoint: Net Clinical Benefit † at 12-month FU
* Exclude ACS with + biomarker; prior DES Rx;SVG target** Stratified by DM and Institution; not blinded† composite endpoint of all-cause death, MI, CVA and major bleeding
DAPT for 3 months DAPT for 12 months N = 1,560 N= 1,560
Feres et al. AHJ 2012:164:810 e3Feres et al. TCT 2013 LBCT
Clinical FU at 1, 3, 6, 12 and 18 months and yearly up to 3 yrs
Ischemic Endpoints By DAPT Duration In Randomized Trials
Adapted from t Gwon et al. ACC 2011tt Valgimigli et al. ESC 2011ttt Park et al. NEJM 2010;362:1374tttt Feres et al. TCT 2013 LBCT
*Cardiac death / MI / TVR**Death / MI, CVA, Revasc***Death/MI/Revasc
EXCELLENT t PRODIGY tt REAL-LATE/ OPTIMIZE tttt ZEST-LATE ttt
6 mos (n=957) 6 mos (n=1546) 12 mos (n=1344) 3 mos (n=1563)12 mos (n=970) 24 mos (n=1500) 24 mos (n=1357) 12 mos (n=1556)
Major Bleeding (TIMI or GUSTO/REPLACE 2* ) By DAPT Duration In Randomized Trials
Adapted from t Gwon et al. ACC 2011tt Valgimigli et al. ESC 2011ttt Park et al. NEJM 2010;362:1374tttt Feres et al. TCT 2013 LBCT
0
0.5
1
1.5
2
2.5
3
0.3
0.6
0.1
0.70.6
1.6
0.2
0.8
% P
atie
nts
EXCELLENT t PRODIGY tt REAL-LATE/ OPTIMIZE tttt* ZEST-LATE ttt
6 mos 6 mos 12 mos 3 mos 12 mos 24 mos 24 mos 12 mos
P=0.42 P=0.04 P=0.35 P=0.66
Type II, III or V BARC Bleeding: PRODIGY
No. at Risk24-month clopidogrel 987 925 884
6-month clopidogrel 983 919 881
Valgimigli et al. Circulation 2012; 125:2015-2026
0 180 360 540 7200
4
8
12 24 mo DAPT 6 mo DAPT
%CEC adjudicated
Hazard ratio: 0.46 (0.1-0.69)
P=0.00018 7.4
3.5
PRODIGY BARC Bleeding Categories
Mehran et al. Circ 2011;123:2736-2747
BARC 2* BARC 3 BARC 50
2
4
6
8
10
4.0
2.5
0.91.5 1.4
0.5
24 mo DAPT 6 mo DAPT
%
*BARC 2 “Any overt, actionable sign of hemorrhage that…meets at least one of the following criteria: (1) requiring nonsurgical, medical intervention by a healthcare professional, (2) leading to hospitalization or increased level of care, or (3) prompting evaluation…no change in hemoglobin, blood transfusion or hemodynamic sequelae are required”
P=0.001
P=0.075
P=0.029
OPTIMIZE : NACCE at 1 Year(All-Cause Death, MI, Stroke, Major Bleeding)
Divided into 4 subsets and 1:1 randomization was performed
31 patients excluded - 16 withdrawal of consent - 15 Met exclusion criteria
E-ZES with 3-month DAPT (N=1059) Standard therapy (N=1058)
Diabetes mellitusSubset (N=292)
Acute coronary syndromeSubset (N=601)
Short-length DESSubset (N=681)
Long-length DESSubset (N=543)
E-ZES(N=146)
R-ZES(N=146)
E-ZES(N=301)
R-ZES(N=300)
E-ZES (N=341)
SES(N=340)
E-ZES(N=271)
EES(N=272)
E-ZES with 3-month DAPTStandard TherapyOther DES with 12-month DAPT
Kim et al. JACC 2012;60:1340-1348Primary Endpoint: CV death, MI, ST, ID-TVR, Bleed (TIMI major & minor)
RESET: Clinical Events Through 1 Year
4.7
0.8
0.2 0.2
4.7
1.3
0.30.6
0
1
2
3
4
5
CV Death, MI, ST,ID-TVR, Bleed*
Death, MI, ST Def/Prob ST** Major Bleed
E-ZES + 3 month DAPT (n=1,059) Standard Therapy (n=1,058)
% P
atie
nts
Adapted from Kim et al. JACC 2012 Sep 5 (e-Pub ahead of print)
*Primary Endpoint: (Assumed 10% with N.I. margin 4% for absolute difference in risk)**SORT OUT III / ENDEAVOR IV / PROTECT / KAMIR
40 41 8 11 2 3 2 6
ISAR-SAFEStudy Flowchart
1st FU: 1 month after randomization2nd FU: 6 months after randomization (at least one day after
study drug cessation)
3rd FU: 9 months after randomization (at least 3 months after study drug cessation)
Randomization
Continuous Clopidogrel therapy for 5 to 8 months
Placebofor 6 months
Clopidogrel 75 mg/dfor 6 months
Drug- Eluting Stenting
Follow Up
0
1st
9th
6th
- 8th to -5th
Primary Analysis 2015
PEP = death,MI,stent thrombosis,stroke,TIMI major bleed
Study treatment period 12-30 mStudy observation period 30-33m
DAPT: Study Design
20
Eligible for Enrollment after PCI• Any PCI with DES or BMS• >18 years of age• No contradictions to dual antiplatelet therapy • Able and willing to provide written informed consent
Eligible for Randomization at 12 mStratified by DES v BMS, drug type, and
complexity (ACS or lesion-based)
Not Eligible for Randomization at 12 m
• Death• MI or repeat PCI at > 6 weeks• CABG• Stroke• Major Bleed
12 m DAPT Arm
Aspirin + blinded placebo
30 m DAPT Arm
Aspirin + blinded thienopyridine
Primary analysis DES treated subjects, 12-30mSecondary analysis propensity matched BMS to
DES subjects 0-30m2 co-primary endpoints: stent thrombosis and
MACCE (death, myocardial infarction or stroke)Powered safety endpoint: major bleeding (GUSTO)
Total 33 month follow-upMauri, Kereiakes et al AHJ 2010;160:1038-1041