Transcript ESC, Hotline III, Paris, August, 30, 2011 PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY M.

ESC, Hotline III, Paris, August, 30, 2011
PROlonging Dual
antiplatelet treatment after
Grading stent-induced
Intimal hyperplasia studY
M. Valgimigli, MD, PhD
University of Ferrara, ITALY
On behalf of the PRODIGY
Investigators
Drivers for Duration of Dual Antiplatelet therapy Post-Stenting
Data suggest that certain patient population
(e.g. high risk for thrombotic events, patients
after SES or PES implantation) may benefit from
IA
prolonged DAPT beyond12
1 year
.
NSTEACS:
Months
IB
STEMI:
12DAPT
Months
Recent data suggest that
for 6 months mayIIa C
IB
Indication to the PCI procedure
….3 lines below
be sufficient because late and very late stent thrombosis
correlate poorly with discontinuation of DAPT
Type of implanted stent(s)
DES:
 because
6 to 12ofMonths
If the risk of morbidity
bleeding outweights
the anticipated benefit
afforded
by thienopyridine therapy,
 12
Months
I B*
earlier discontinuation should be considered (I C)
*: DUKE heart registry, JAMA 07; 159-68
Quoted Registries by Guidelines
for prolonged DAPT after DES
% D/MI
P=0.02
P=0.50
50%
RRR
637
579
417 1,976
18 Month Events After Clopidogrel
Discontinuation at 6 Months Stratified
by Stent Type*
% D/MI
24 Month Events in Patients who
Discontinued or did not Discontinue Clopidogrel
at 6 Months Stratified by Stent
73%
RRR
244
499
N=1,216
*N=3 *N=24
Eisenstein EL et al, JAMA 2007
Pfisterer M et al, J Am Coll Cardiol 2006
PRODIGY Study Flow Chart
Intent-to-stent
1:1:1:1
Balancing
Randomization
Xience V®
Taxus®
BMS
Endeavor®
30-Days
1:1
1° Endpoint Randomization
Short
DAPT
Aspirin
Prologned
DAPT
Clopidogrel
6 mos
Aspirin
6 mos
6 Mos*
Clopidogrel
6 mos
12 mos
12 mos
12 mos
18 mos
18 mos
18 mos
24 mos
24 mos
*: <6 months clopidogrel was allowed in BMS pts with stable CAD at the time of PCI
24 Mos
2,697 ASSESSED FOR ELIGIBILITY
75%
694 Excluded, 353 Not Meeting Inclusion Criteria
232 Refused to Participate, 109 Operator’s choice
2,013 randomly allocated to recieve one of the four study stent types
501 randomized to EES
499 received EES
10 received POBA for ≥1 lesion
4 had ≥1 failed treated lesion
5 died before 30 days
1 withdrew at 30 days
505 randomized to PES
498 received PES
13 received POBA for ≥1 lesion
2 had ≥1 failed treated lesion
11 died before 30 days
4 withdrew at 30 days
502 randomized to ZES
500 received ZES
12 received POBA for ≥1 lesion
4 had ≥1 failed treated lesion
7 died before 30 days
2 withdrew at 30 days
505 randomized to BMS
502 received BMS
14 received POBA for ≥1 lesion
2 had ≥1 failed treated lesion
10 died before 30 days
3 withdrew at 30 days
1,970 eligible for
randomization at 30 days
983
983
987
987
Months DAPT
DAPT
66 Month
24 Month
Months DAPT
DAPT
24
4 Lost to follow-up
99.6%
3 Lost to follow-up
Ff
984
2 year follow-up
f
Ff
979
2 year follow-up
f
Clopidogrel and Dual Anti-Platelet
Therapy Use
Compliance to DAPT
(%)
Compliance to Clopidogrel
(%)
•24 Month DAPT (n=987)
6 Month DAPT (n=983)
100
100
99.4
98.3 96.9 95.7
100
83.6
80
100
60
40
40
20
20
3.5
1 Mo
6 Mo
100
80
60
0
100
12 Mo
0.9
18 Mo
98.8
0
3.4
1 Mo
P<0.001 for all time points from 6 months onwards
95.9
94.7
0.6
0.3
83.1
0.5
24 Mo
97.4
6 Mo
12 Mo
18 Mo
24 Mo
Primary Endpoint
Overall Death, MI or CVA
CEC adjudicated
24 mo DAPT
12
6 mo DAPT
10.1
10.0
8
%
P=0.91
4
Hazard Ratio: 0.98 (0.74-1.29)
0
0
No. at Risk
24-Month Clopidogrel
6-Month Clopidogrel
180
987
983
360
925
540
720
884
919
881
Secondary Endpoint
Death from any cause
24 mo DAPT
12
6 mo DAPT
P=0.98
10
%
8
6.6
6.6
6
4
2
Hazard Ratio: 1.00 (0.72-1.40)
0
0
No. at Risk
24-Month Clopidogrel
6-Month Clopidogrel
987
983
180
360
925
540
720
884
919
881
Secondary Endpoint
Death from any cause or MI
CEC adjudicated
24 mo DAPT
12
6 mo DAPT
9.6
8.9
P=0.62
%
8
4
Hazard Ratio: 1.07 (0.80-1.43)
0
0
No. at Risk
24-Month Clopidogrel
6-Month Clopidogrel
987
983
180
360
925
540
720
884
919
881
Landmark Analysis
CEC adjudicated
Death from any cause, MI or CVA
adjudicated
from CEC
6 months
onwards
24 mo DAPT
12
10
P=0.53
HR: 0.89 (95%CI: 0.64-1.25)
8
%
6 mo DAPT
7.2
6.4
6
4
2
0
0
No. at Risk
24-Month Clopidogrel
6-Month Clopidogrel
180
360
963
961
934
933
540
913
916
720
893
895
Key Safety Endpoint
Type II, III or V BARC bleeding
CEC adjudicated
24 mo DAPT
6 mo DAPT
12
P=0.00018
8
%
7.4
4
3.5
Hazard Ratio: 0.46 (0.1-0.69)
0
0
No. at Risk
24-Month Clopidogrel
6-Month Clopidogrel
180
987
983
360
925
540
720
884
919
881
Bleeding Events and RBC Transfusion
CEC adjudicated
P=0.00018
P=0.00033
%
P=0.037
P=0.041
P=0.041
Bleeding Academic Research Consortium
Summary
Our study failed to show that prolonging
DAPT for 24 months is superior to 6
month duration of Tx in pts receiving
1 or 2 gen DES or at least 1 month after
BMS
While we cannot rule out the possibility
that a smaller than previously anticipated
benefit may exist, the clear increase
in bleeding, transfusion and net adverse
clinical events, suggests that
current recommendations may have
overemphasized the benefit over the risk
of combined long-term aspirin and
clopidogrel
ENDPOINTS HAZARD RATIO
(95% CI)
P-VALUES
P=0.91
D/MI/CVA
D/MI
P=0.62
D/CVA
P=0.57
Def ST
P=0.80
Key safety EP
P<0.001
TIMI Major Bleed
P=0.041
RBC Transfusion
P=0.041
Net Adverse
Clinical Events
P=0.025
1.5
24-month DAPT better
1
0.5
6-month DAPT better
0