1. How and why this study may change my practice ?
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

2. 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

3. 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.

4. 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

5. 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

6. 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

7. 1st Gen DES vs. BMS for STEMI 8 Trials < 1000 patients each
Kastrati et al Euro Heart Journal : 2706

8. DES are superior to BMS RE INTERVENTION STENT THROMBOSIS
Kastrati et al Euro Heart Journal : 2706

9. 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!

10. No differences in characteristics among 2ND Gen DES VS
No differences in characteristics among 2ND Gen DES VS. BMS in STEMI studies
COMFORTABLE AMI
HORIZON AMI
EXAMINATION
BES
BMS
PES
EES
# 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
Stent Length
25.2
24.1
30.8
27.3 23
# of stents
1.3
1.5
1.4
1.37
1.36
IIB/IIIA
48.0
45.7
52.0
51.5
53.3
Prasugrel
40.2
41.1
On DAPT at 12 months
80.6
81.6
73.1
63.9
97.9
89.9

11. TLR and ST rates BES & EES < PES No differences among BMS types
COMFORTABLE AMI
HORIZON AMI
EXAMINATION
BES
BMS
PES
EES
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
ID TLR
1.6
5.7*
7.5*
2.2
5.1*
Definite ST
0.9
2.6
3.0
1.9*
Definite /probable ST
2.5
3.1
3.4
2.5*
Stroke
1.1
0.7
1.0
N/A
* Statistically significant as compared to DES

12. Primary PCI with bivalirudin anticoagulation
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 Double-blind R
1:1
Prasugrel
Clopidogrel
All pts: 30 d, 6 mo, 1 yr, 2 yr, 3 yr
Pharmacology rand only: 15 mo
Clinical FU:

13. 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

14. Can the STEMI results in LEADERS replicate with second generation DES25
1-year HR
0.40 [0.19 to 0.87]
P = 0.02*
2-year HR
0.40 [0.20 to 0.80]
P = 0.01*
3-year HR
0.43 [0.23 to 0.84]
P = 0.01*
BES
SES
8.4%
19.7%
Δ11.3%
21.3% 20
15.9%
-57% 15 %
Δ9.1% 10
10.0%
6.8% 5 6 12 18 24 30 36
Number at risk
BES
135
132
121
120
118
116
108
SES
140
138
115
114
111
106
101
Months

15. 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