Ponencia realizada por el Dr. Montalescot y presentada por el Dr. José Antonio Gómez Hospital en la Reunión EuroIMAT 2020, celebrada en Barcelona (20 y 21 de febrero de 2020).

1. Low Molecular Weight Heparin in STEMI
G. Montalescot
G. Montalescot, Research Grants to the Institution or Consulting/Lecture/CME Fees available at www.action-coeur.org

2. Change in the opponent:
G Montalescot
Pitié Salpêtrière
Paris
JA Gómez Hospital
Hospital Universitari Bellvitge
L’Hospitalet. Barcelona
No conflicts of interest

3. Primary PCI: Periprocedural pharmacotherapy
Antiplatelet Therapy
Potent P2Y12 inhibitor (Prasugrel orTicagrelor)
Or
Clopidogrel
Aspirin
GP IIb/IIIa inhibitors
Cangrelor
Anticoagulant Therapy
Unfractioned Heparin
Enoxaparin
Bivalirudin
Fondaparinux

4. ENOXAPARIN IN ELECTIVE PCI

5. STEEPLE TRIAL
Montalescot G et al. N Engl J Med 2006; 355: 1006.
Non-CABG Major or Minor Bleeding at 48 h
Percent reaching target anticoagulation levels at the
start and end of the procedure

6. STEEPLE: Safety and Efficacy
Quadruple End Point: All-Cause Death, MI, UTVR 30d and Major Bleeding
up to 48 h
p= all NS
Ischemic End Point at 30 days
Montalescot G et al. N Engl J Med 2006; 355: 1006.

7. IV Enoxaparin
Predictable and easy-to-use anticoagulation

8. ENOXAPARIN IN STEMI
(NON PRIMARY PCI)

9. ExTRACT TIMI 25 Trial
Antman EM, et al. N EnglJ Med. 2006;354:1477-1488.

10. ExTRACT–TIMI 25: fibrinolysis+/- PCI
Antman EM, et al. N EnglJ Med. 2006;354:1477-1488.

11. STEMI: RCTs Meta-analysis
Odds ratio
.2 1 5
Study % Weight
Odds ratio
(95% CI)
0.92 (0.82,1.02)ExTRACT 79.0
1.27 (0.86,1.87)ASSENT 3 Plus 5.0
0.89 (0.68,1.16)ASSENT 3 12.8
0.54 (0.23,1.27)BAIRD 1.7
0.68 (0.15,3.09)ENTIRE 0.4
0.90 (0.36,2.25)HART II 1.1
0.92 (0.84,1.01)Overall (95% CI)
ENOX
Better
UFH
Better
7.1%6.6%
Fixed effects
Random Effects
.2 5
0.92 (0.84,1.01)
Odds ratio
.2 1 5
Study
Odds ratio
(95% CI)
0.68 (0.59,0.78)ExTRACT
0.59 (0.37,0.95)ASSENT 3 Plus
0.62 (0.44,0.87)ASSENT 3
0.70 (0.38,1.28)BAIRD
0.14 (0.04,0.52)ENTIRE
1.00 (0.37,2.72)HART II
0.66 (0.59,0.74)Overall (95% CI) Fixed effects
Random Effects
0.64 (0.53,0.78)
5.1%3.4%
UFH
Better
ENOX
Better
.2 5
N=27,131
30 days
Death Re-infarction
ExTRACT
ASSENT-3 Plus
ASSENT-3
BAIRD
ENTIRE
HART II
OVERALLOVERALL
Odds ratio
.2 1 5
Study % Weight
Odds ratio
(95% CI)
0.92 (0.82,1.02)ExTRACT 79.0
1.27 (0.86,1.87)ASSENT 3 Plus 5.0
0.89 (0.68,1.16)ASSENT 3 12.8
0.54 (0.23,1.27)BAIRD 1.7
0.68 (0.15,3.09)ENTIRE 0.4
0.90 (0.36,2.25)HART II 1.1
0.92 (0.84,1.01)Overall (95% CI)
ENOX
Better
UFH
Better
7.1%6.6%
Fixed effects
Random Effects
.2 5
0.92 (0.84,1.01)
Odds ratio
.2 1 5
Study
Odds ratio
(95% CI)
0.68 (0.59,0.78)ExTRACT
0.59 (0.37,0.95)ASSENT 3 Plus
0.62 (0.44,0.87)ASSENT 3
0.70 (0.38,1.28)BAIRD
0.14 (0.04,0.52)ENTIRE
1.00 (0.37,2.72)HART II
0.66 (0.59,0.74)Overall (95% CI) Fixed effects
Random Effects
0.64 (0.53,0.78)
5.1%3.4%
UFH
Better
ENOX
Better
.2 5
N=27,131
30 days
Death Re-infarction
ExTRACT
ASSENT-3 Plus
ASSENT-3
BAIRD
ENTIRE
HART II
OVERALLOVERALL

12. ENOXAPARIN IN STEMI: PRIMARY PCI

13. FINESSE: Improved safety and Efficacy in Facilitated PCI
Montalescot G. et al. JACCCardiovasc Interv 2010; 3(2): 203.

14. FINESSE: Enoxaparin in Primary PCI
Montalescot G. et al. JACCCardiovasc Interv 2010; 3(2): 203.
Non-randomized comparison
n= 2452

15. FINESSE: Adjusted Odds Ratios for Efficacy and Safety Endpoints
LMWH vs. UFH
Endpoint OR 95% CI P
TIMI major bleeding 0.56 0.31 – 0.99 0.04
Death/complications of MI to day 90 (1°)* 0.73 0.52 – 1.03 0.07
Death to day 90 0.59 0.35 – 0.99 0.04
Death or MI to day 30 0.58 0.35 – 0.96 0.03
Death, MI, urg revasc or refr. ischemia to day 30 0.47 0.31 – 0.72 0.0005
Net benefit (death/MI/stroke/major bleeding) 0.64 0.45 – 0.91 0.01
*Hazard ratio (logistic regression model)
Montalescot G. et al. JACCCardiovasc Interv 2010; 3(2): 203.

17. ATOLL : primary PCI
STEMI  Primary PCI
1° EP: Death, Complication of MI, Procedure Failure, Major Bleeding
Main 2° EP: Death, recurrent MI/ACS, Urgent Revascularization
30 days
Randomization as early as possible
Real life population (shock, cardiac arrest included)
No anticoagulation before Rx
Similar antiplatelet therapy in both groups
ENOXAPARIN IV
0.5 mg/kg
with or without GPIIbIIIa
UFH IV
50-70 IU with GP IIbIIIa
70-100IU without GP IIbIIIa
(Dose ACT-adjusted)
Primary PCI
ENOXAPARIN SC UFH IV or SC
ATOLL TRIAL
• Resuscitated cardiac arrest.
• Recurrent ACS.
• Urgent revascularisation.
• Stroke.
• Peripheral or pulmonary
embolism.
Complication of MI:
• Definite Stent Thrombosis (ARC)
• Bailout use GP IIb/IIIa inhibitor
• Non TIMI 3 flow
• ST resolution < 50%
Procedure Failure
Montalescot G, et al. Lancet. 2011;378:693-703

18. ATOLL
Intent-to-Treat and per-protocol

19. ATOLL: Primary end point
Death, Complication of MI, Procedure Failure or Major Bleeding
Montalescot G, et al. Lancet. 2011;378:693-703 Collet JP et al. AmJ Cardiol 2013;112:1367e1372
Per-protocol
RRR = 23%
P = 0.0133.7
28
0
5
10
15
20
25
30
35
40
UFH
ENOX
RRR = 17%
P = 0.07
%ofpatients
0.06
Intention-To-Treat
10
15
5
0
20
25
30
35
40

20. ATOLL: Main secondary end point
Death, Recurrent ACS or Urgent Revascularization
0 5 10 15 20 25 30
0.000.050.100.15
Days
MainsecondaryEPrate
UFH
ENOX
Log-Rank Test
p=0.01
11.3%
6.7%
30d rate (%)
i41%
Intent-To-Treat Per-protocol
i73%
p=0.006
UFH
ENOX
Montalescot G, et al. Lancet. 2011;378:693-703 Collet JP et al. AmJ Cardiol 2013;112:1367e1372

21. ATOLL: Major bleeding
RRR = 54%
P = 0.04
Per-protocol
RRR = 8%
P = NS
Intent-To-Treat
%
%
Montalescot G, et al. Lancet. 2011;378:693-703 Collet JP et al. AmJ Cardiol 2013;112:1367e1372

22. Mortality in ATOLL
Per-protocole
RRR = 64%
P = 0.003
RRR = 40%
P = 0.08
Intent-To-Treat
Montalescot G, et al. Lancet. 2011;378:693-703 Collet JP et al. AmJ Cardiol 2013;112:1367e1372

23. Meta-analysis enoxaparin vs. UFH in PCI
 48%
 34%
J. Silvain et al. BMJ 2012; 344:e553.

24. Updated Meta-Analysis
Wang Hai long et al. Open Med 2018; 13: 359–365
Fixed-effect meta-analysis for Death
Fixed-effect meta-analysis for Major Bleeding

25. ATOLL in the real life (e-PARIS Registry)
Brieger D et al. Cathet Cardiovasc Interv 2011; 77: 182.

26. ATOLL in the real life
Brieger D et al. Cathet Cardiovasc Interv 2011; 77: 182.

27. GUIDELINES AND RECOMMENDATIONS

28. 2017 ESC STEMI recommendations

29. Anticoagulant therapy in ESC STEMI guidelines

30. 1. BEFORE PCI, BOLUS of 0.5mg/Kg IV (or in
arterial sheath), at first medical contact
2. DURING PCI, If PCI not finished 2hrs later,
SECOND BOLUS of 0.25mg/kg
3. AFTER PCI, 40mg/subQ od, starting right
after procedure, during Hospital stay.
Weight
(kg)
Volume
(mL)
80 7.1
85 7.5
90 8
95 8.4
100 8.8
105 9.3
110 9.7
115 10.2
Dilute 300 mg of
enoxaparin in a 50 mL
bag of D5W or NS
Enoxaparin in STEMI with Primary PCI

31. Post-procedural anticoagulation
Results will be available in December 2020

32. CONCLUSIONS:

33. Conclusions
• Enoxaparin can be used for all MI and PCI patients.
• Dose IV 0,5 mg/Kg. No need for ACT monitoring.
• Same dose with or without GPIs.
• Better safety/efficacy than UFH.