i.v. enoxaparin or unfractionated heparin in primary pci: acute and long-term results g. m...
TRANSCRIPT
![Page 1: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/1.jpg)
I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results
G. MONTALESCOT, DISCLOSURE: Research Grants to the Institution or Consulting/Lecture Fees from Abbott Vascular, Astra-Zeneca, Bayer, Biotronik, Boehringer-Ingelheim, Boston Scientific, Cleveland Clinic Foundation, Cardiovascular Research Foundation, Cordis, Daiichi-Sankyo, Duke institute, Eli-Lilly, Europa, Fédération Française de Cardiologie, Fondation de France, GSK, ICM, INSERM, Lead-up, Medtronic, Menarini, Nanospheres, Novartis, Pfizer, Sanofi-Aventis Group, Servier, Société Française de Cardiologie, The Medicines Company, TIMI group.
ATOLL: Acute STEMI Treated with primary PCI and intravenous enoxaparin Or UFH to Lower ischemic and bleeding events at short- and Long-term follow-up (Investigator-driven study)
G. Montalescot, M. Cohen, P. Goldstein,
K. Huber, C. Pollack, U. Zeymer, E. Vicaut
for the ATOLL investigators
![Page 2: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/2.jpg)
Intravenous enoxaparin vs. UFH in PCI
Primary PCI of STEMI
(ATOLL)
Secondary PCI of STEMI
(ExTRACT-PCI)
Elective PCI
(STEEPLE) 57%Major Bleeding
(p=0.004)
23%Death or re-MI
(p<0.001)
Montalescot G et al. N Engl J Med 2006;355:1006 –17Gibson MC et al. J Am Coll Cardiol 2007;49:2238–46
?
![Page 3: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/3.jpg)
ATOLL Trial design
STEMI Primary PCI
30-day and 6-month results
Randomization as early as possible (MICU +++)Real life population (shock, cardiac arrest included)
No anticoagulation and no lytic before Rx
Similar antiplatelet therapy in both groups
ENOXAPARIN IV0.5 mg/kg
with or without GPIIbIIIa
UFH IV 50-70 IU with GP IIbIIIa
70-100IU without GP IIbIIIa(Dose ACT-adjusted)
IVRS
Primary PCI ENOXAPARIN SC UFH IV or SC
![Page 4: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/4.jpg)
Trial organization
ACTION Study Group (Academic Research Organization, Paris):
1-Coordinating Center: Institute of Cardiology, Pitié-Salpêtrière Hospital, Paris 2-Sponsor: AP-HP (Assistance Publique-Hôpitaux de Paris) 3-Data center, Statistics: Unité Recherche Clinique, Lariboisière Hospital, Paris 4-International CRO: Pierrel-Hyperphar 5-Funding: AP-HP and unrestricted research grant from Sanofi-Aventis Group
Steering Committee: G. Montalescot (Chair, France), M. Cohen (USA), P. Goldstein (France), K. Huber (Austria), C. Pollack (USA), E. Vicaut (France), U. Zeymer (Germany)
Data Safety Monitoring Board: A. Cohen (Chair, France), M. Cucherat (France), A. Gitt (Germany)
Core Laboratory: R. Dumaine, A. Samadi
Clinical Event Committee: F. Philippe, P. Sabouret, F. Boccara, A. Bellemain, O. Gournay
![Page 5: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/5.jpg)
Main objectives
• 1° EP:– All-cause mortality at D30, – Complications of MI at D30 [resuscitated cardiac arrest,
recurrent MI/ACS, urgent revascularization, stroke, peripheral or pulmonary embolism],
– Procedure failure [definite stent thrombosis; B.O. use of GpIIB/IIIa; Non-TIMI 3 flow after PCI; ST resolution < 50% after PCI],
– Non-CABG major bleeding during hospitalization
• Main 2° EP: All-cause mortality, Recurrent ACS or Urgent revascularization at D30
• Main safety EP: Non-CABG major bleeding (STEEPLE definition) during hospitalization
![Page 6: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/6.jpg)
FINAL 30-DAY RESULTS
![Page 7: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/7.jpg)
Selected Baseline Characteristics
UFH (n=460)
ENOXAPARIN (n=450)
Age, median (Q1;Q3) Age > 75
60 (52; 70)17% (80)
59 (52; 71)19% (85)
Pre-hospital randomization 71% (325) 71% (318)
Shock and/or cardiac arrest before sheath, % (n) 5% (24) 4% (17)
Time from symptom onset to randomization—hr, median (Q1;Q3)
2h19(1h26; 4h37)
2h33(1h29; 4h50)
Radial artery access, % (n) Other artery access, % (n)
66% (305)34% (155)
69% (309) 31% (141)
Glycoprotein IIb/IIIa inhibitors,% (n) 83% (382) 77% (347)
Clopidogrel < 300mg > 300 and < 600mg > 600 and < 900mg > 900mg
37% (171) 37% (172) 25% (113)
1% (4)
37% (168)39% (174) 22% (101)
2% (7)
![Page 8: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/8.jpg)
Primary EndpointDeath, Complication of MI, Procedure Failure or Major Bleeding
33.7
28
0
5
10
15
20
25
30
35
40
UFHENOX
RRR = 17% P = 0.07
% o
f pa
tien
ts 0.06
![Page 9: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/9.jpg)
Main Secondary Endpoint (ischemic) Death, Recurrent ACS or Urgent Revascularization
0 5 10 15 20 25 30
0.0
00
.05
0.1
00
.15
Days
Mai
n se
cond
ary
EP
rate UFH
ENOX
Log-Rank Test
p=0.01 11.3%
6.7%
30d rate (%)
41%
![Page 10: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/10.jpg)
Consistent therapy Pre-specified analysis: no protocol violation (88%)
0.1 1.0 10
Only one heparin
More than one heparin
Only one heparin
More than one heparin
Relative Risk
IV 0.5mg/kg Enoxaparin better IV UFH better
0.76 (0.61-0.94)
1.51 (0.91-2.50)
RR (95%CI)
0.76 (0.61-0.94)
1.51 (0.91-2.50)
1 � end point
Main 2� end point
![Page 11: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/11.jpg)
Death or Complication of MIDeath, resuscitated cardiac arrest, recurrent ACS, Urg Revasc,
stroke, peripheral or pulmonary embolism
0 5 10 15 20 25 30
0.0
00
.05
0.1
00
.15
Days
De
ath
orC
om
plic
atio
n o
f MI r
ate
UFHENOX
Log-Rank Test
p=0.02 12.4%
7.8%
30d rate (%)
37%
![Page 12: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/12.jpg)
Death or resuscitated cardiac arrest
Death (any)
0 5 10 15 20 25 30
0.00
0.02
0.04
0.06
0.08
0.10
DaysDea
thor
resu
scita
ted
card
iac
arre
stra
te
UFHENOX Log-Rank Test
p=0.049 7.0%
4.0%
30d rate (%)
0 5 10 15 20 25 30
0.00
0.02
0.04
0.06
0.08
0.10
Days
Dea
thra
te
UFHENOX Log-Rank Test
p=0.08 6.3%
3.8%
30d rate (%)
40% 42%
6.3%
3.8%
7.0%
4.0%
![Page 13: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/13.jpg)
Safety Endpoints
Protocole definitions (STEEPLE)
NS
![Page 14: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/14.jpg)
Death, Complication of MI or Major bleedingNet clinical benefit
15
10,2
0
2
4
6
8
10
12
14
16
UFHENOX
RRR = 32% P = 0.03
% o
f pa
tien
ts
![Page 15: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/15.jpg)
6-month Follow-up
![Page 16: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/16.jpg)
6-month results
• Follow-up on mortality
• 100% follow-up
• We used a Cox regression model to identify independent predictors of death at 6 months. We firstly performed univariate analysis and significant variables were introduced into a stepwise cox regression model
![Page 17: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/17.jpg)
Death over 6 months
0 1 2 3 4 5 6
0.00
0.02
0.04
0.06
0.08
0.10
Months
Dea
th
ENOX
UFH
Log Rank Test: p=0.11
6.3%
7.0%7.2%
3.8%
4.5%4.7%
r=2.5%
r=2.5%r=2.5%
![Page 18: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/18.jpg)
Independent correlates of death at 6 months
Variables HR[95%CI] Pvalue
Beta blockers, yes vs. no 0.16 [0.08;0.32] <.0001
KILLIP II,III,IV vs. I 3.87 [2.02;7.4] <.0001
Age >75 vs. <75 4.01 [2.2;7.29] <.0001
ACE yes vs. no 0.32 [0.16;0.66] 0.0021
MI location, anterior vs. other 2.24 [1.27;3.94] 0.0052
Prior heart failure, yes vs. no 4.57 [1.37;15.31] 0.0137
Prior COPD, yes vs. no 3.15 [1.05;9.39] 0.0401
Systolic BP [mmHg] (10 units increase) 0.87 [0.77;0.97] 0.0149
Prior stroke, yes vs. no 3.10 [1.14;8.48] 0.0273
![Page 19: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/19.jpg)
Conclusions
In this 1st head-to-head comparison between two anticoagulants in primary PCI, i.v. enoxaparin:
• Reduced serious ischemic events, on top of intense antiplatelet therapy
• Had a good safety profile, with a superior net clinical benefit
• Tended to reduce mortality over 6 months
![Page 20: I.V. Enoxaparin or Unfractionated Heparin in Primary PCI: Acute and Long-term results G. M ONTALESCOT, DISCLOSURE : Research Grants to the Institution](https://reader031.vdocuments.net/reader031/viewer/2022032015/56649cc35503460f9498baa6/html5/thumbnails/20.jpg)
Special Thank to:
INVESTIGATORS – Austria: WR. Benzer, K. Huber, F. Leisch, F. Weidinger – France: F. Adnet, M. Angioi, B. Barberon, JF. Benezet, JL. Bonnet, J. Boschat, B. Boulanger, D. Carrie, T. Chouihed, P. Coste, Y. Cottin, H. Courcoux, C. Cuvier, N. Danchin, JL. Ducasse, F. Duclos, P. Ecollan, S. Elhadad, E. Filippi, M. Freysz, F. Funck, S. Gallula, B. Gelée, A. Greffet, P. Henry, A. Jacquemin, T. Joseph, JM. Lablanche, H. Lardoux, H. Le Breton, B. Lederman, A. Margenet, G. Mehu, O. Nallet, F. Paganelli, M. Pansieri, L. Payot, C. Pouges, E. Salengro, C. Spaulding, G. Steg, O. Stibbe, E. Teiger, M. Thicoipe, C. Thuaire, J. Treuil, O. Wittenberg, O. Wolf – Germany: D. Andresen, C. Axthelm, Fischer, E. Girth, E. Hauptmann, U. Zeymer – USA: M.Cohen, F. ShamoonCOMMITTEES – A Appaix-Bellemain, F Boccara, A Cohen, M. Cohen, M Cucherat, R Dumaine, A Gitt, P Goldstein, O Gournay, K Huber, F Philippe, C Pollack, P Sabouret, A Samadi, E Vicaut, U ZeymerPIERREL Research– L. Basso, L. Merlini, M. MazzoleniACTION study Group – ME. Assossou, M. Aout, B. Bertin, D. Brugier, JP. Collet, M. Courreges-Viaud, V. Gallois, P. Gallula, V. Jouis, S. Kabla, C. Misse, G. Ngouala, A. Pena, S. Paulsrud, N. Vignolles