COMFORTABLE AMI
How and why this study may
change my practice ?
Ron Waksman, MD, FACC, FSCAI
Professor of Medicine, Georgetown University,
Director Cardiovascular Research Medstar Heart Institute
Associate Director of Cardiology , Washington Hospital Center,
Washington, DC
Potential conflicts of interest
Speaker’s name: Ron Waksman, MD
x I have the following potential conflicts of interest to report:
x Research contracts: Boston Scientific, Abbott Vascular,
Medtronic, Biotronik
x Consulting to Biotronik
 Employment in industry
 Stockholder of a healthcare company
 Owner of a healthcare company
 Other(s)
 I do not have any potential conflict of interest
Conclusions
Human pathologic analysis clearly indicate that healing is delayed by DES in
the setting of plaque rupture vs. stable angina and that an increased risk of
late thrombotic events should be expected in this setting.
We believe there is a need for more rigorous larger randomized controlled
trials before new technologies are used for unapproved indications such as
AMI. Until these data become available, routine implantation of DES for AMI
Cannot be recommended.
COMFORTABLE AMI
is a high quality study
• Testing new bioabsorbable polymer technology of
DES for the STEMI indication
• Prospective, multinational multicenter, two arm,
randomized 1:1.
• Strong study organization: monitoring, steering
committee, DSMB, CEC, angio and IVUS/OCT core labs
• Enrollment completed in 2 years with > 97% available
clinical follow-up at one year
COMFORTABLE AMI
Main study Weakness
• Control was a BMS without a track record in
clinical trials or in STEMI
• The study is underpowered to detect specific
components of the primary endpoint which
combined safety and efficacy endpoints
• The one year follow-up does not enable to
examine the performance of the device after
complete degradation (9 M) of the polymer
• Did not compared with second Gen DES
Which Stent are you using for AMI?
• If you mainly BMS user you should switch to
DES
• The Comfortable AMI is concordant with all
the prior DES versus BMS studies for the use of
DES for the AMI indication
• DES are superior to BMS for re intervention
across all AMI trials, without safety issues
• Guidelines should reflect the data and changed
1st Gen DES vs. BMS for STEMI
8 Trials < 1000 patients each
Kastrati et al Euro Heart Journal 2007 28: 2706
DES are superior to BMS
RE INTERVENTION
Kastrati et al Euro Heart Journal 2007 28: 2706
STENT THROMBOSIS
Which Stent are you using for AMI?
The Question is
• If you are mainly a DES user should you switch
to the BES technology?
Unfortunately
• The Comfortable AMI did not address this
question
Can we compare across trials?
• Probably not, but I could not resist!
No differences in characteristics among
2ND Gen DES VS. BMS in STEMI studies
COMFORTABLE AMI
HORIZON AMI
EXAMINATION
BES
BMS
PES
BMS
EES
BMS
# of pts
575
582
2257
749
751
747
Age
60.7
60.4
59.9
59.3
61
62
Gender
80.5
78.2
77.0
76.0
84.4
81.7
Diabetes
14.6
15.5
16.1
15.2
18
16
Smoker
47.9
52.3
46.3
51.9
72
72
Stent Length
25.2
24.1
30.8
27.3
23
23
# of stents
1.3
1.3
1.5
1.4
1.37
1.36
IIB/IIIA
48.0
45.7
52.0
51.5
53.3
51.5
Prasugrel
40.2
41.1
0
0
0
0
On DAPT at
12 months
80.6
81.6
73.1
63.9
97.9
89.9
TLR and ST rates BES & EES < PES
No differences among BMS types
COMFORTABLE AMI
HORIZON AMI
EXAMINATION
BES
BMS
PES
BMS
EES
BMS
MACE
4.3
8.7*
8.1
8.0
11.9
13.9
Cardiac Death
2.9
3.5
2.4
2.7
3.2
2.8
Re infarction
0.5
2.7 *
3.7
4.5
1.4
2.1
Q- MI
0.4
1.2
2.0
1.9
1.3
2.0
ID TLR
1.6
5.7*
4.5
7.5*
2.2
5.1*
Definite ST
0.9
2.1
2.6
3.0
0.5
1.9*
Definite
/probable ST
2.5
3.7
3.1
3.4
0.9
2.5*
Stroke
1.1
0.7
1.0
0.7
N/A
N/A
* Statistically significant as compared to DES
HORIZONS-AMI II
Harmonizing Outcomes with Revascularization and Stents in AMI II
7,000 – 10,000 pts with STEMI
Aspirin
Prasugrel (open-label)
Primary PCI with bivalirudin anticoagulation
Stent randomization eligible
R
1:1
Promus Element DES
Omega BMS
Follow-up at 30 days
Pts without MACE or bleeding
Prasugrel
Clinical FU:
R
1:1
Double-blind
Clopidogrel
All pts: 30 d, 6 mo, 1 yr, 2 yr, 3 yr
Pharmacology rand only: 15 mo
Are 2nd gen DES safer than
BMS in STEMI patients?
Hypothesis 1:
• Polymer covered stent are less thrombogenic
Hypothesis 2:
• Reducing restenosis is associated with the reduction of late
stent thrombosis and re infarction
Hypothesis 3:
• It is possible that high prasugrel use reduce the overall event
rate in comfortable AMI
Hypothesis 4:
• Will biodegradable polymer, when compared to durable, result
with lower event rate after one year? In LEADERS it was shown
only after 3 years
Can the STEMI results in LEADERS replicate
with second generation DES
25
1-year HR
0.40 [0.19 to 0.87]
P = 0.02*
BES
SES
3-year HR
2-year HR
0.40 [0.20 to 0.80]
P = 0.01*
0.43 [0.23 to 0.84]
P = 0.01*
19.7%
20
15.9%
-57%
Δ11.3%
15
%
21.3%
Δ9.1%
10
10.0%
8.4%
6.8%
5
0
0
6
12
Number at risk
18
Months
24
30
36
BES
135
132
121
120
118
116
108
SES
140
138
115
114
111
106
101
Comfortable AMI
Should you change your practice
• I am comfortable to switch from BMS to BES
• I am not comfortable to switch from DES to
BES for all patients with AMI yet
• I am eager to see the results of the next study
that will test biodegradable versus durable
polymer DES for AMI patients (Leaders-like
study).
Thank you for the opportunity
to comment on this trial