Ponencia presentada por el Dr. Raúl Moreno Gómez en el directo online ‘Anticoagulación de cine en el paciente mayor’, realizado el 13 de febrero de 2020 en la Casa del Corazón.
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Braveheart. NOAC in AF patients after coronary stenting
1. NOAC in AF patients after coronary stenting
Dr. Raúl Moreno
Hospital La Paz - Madrid, Spain
BRAVEHEART
Fotoretiradadelapelícula“Braveheart”utilizadaparafineseducativos
segúnelart32delaLPI.
2. • 5-7% patients undergoing PCI have indication for oral
anticoagulation due to AF.
• These patients are at high risk of both thrombotic and bleeding
events.
• Treatment: wide variation in clinical practice.
• Two separate aspects of anti-thrombotic treatment:
– Double versus triple therapy.
– NOAC vs vKA.
HOW IMPORTANT IS THIS PROBLEM
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
3. IMPACT OF POST-DISCHARGE BLEEDING AFTER PCI
(ADAPT-DES STUDY)
Impact of post-discharge bleeding vs MI on mortality
8583 patients treated with ≥ 1 DES prospectively followed-up in 10-15 hospitals.
Platelet reactivity evaluated using VerifyNow showed increased risk of events with high PRU.
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
4. BRAVEHEART
NOAC in AF patients after coronary stenting
Dr. Raúl Moreno
Hospital La Paz - Madrid, Spain
Fotoretiradadelapelícula“Braveheart”utilizadaparafineseducativos
segúnelart32delaLPI.
5. ALL OPTIONS CAN BE GOOD, BAD, AND UGLY AT THE SAME
TIME
DAPT Anticoagulation
Prevention of stent
thrombosis &
reinfarction
Prevention of stroke
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
6. DUAL VERSUS TRIPLE THERAPY IN POST-PCI PATIENTS
WITH AF
11,480 patients with AF and
MI or post-PCI (2000-2009)
in Denmark.
Bleeding events accordingly
to the type of anti-thrombotic
therapy.
Triple therapy: the problem of bleeding
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
7. • 583 patients with indications for OAC undergoing PCI (98% stent, 2/3 DES).
• Randomization to doublé (clopi+VKA) vs triple (ASA+Clopi+VKA) therapy.
DOUBLE VERSUS TRIPLE ANTI-PLATELET THERAPY: WOEST
TRIAL
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
8. DOAC VERSUS VKA: THE PUZZLE HAS BEEN COMPLETED
Rivaroxaban
(PIONEER)
Apixaban
(AUGUSTUS)
Dabigatran
(RE-DUAL)
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
9. Significantly lower rates of ISTH major bleeding or CRNMBE with
dabigatran dual therapyProbabilityofevent(%)
0
0 90 180 270 360 450 540 630 720
Time to first event (days)
40
35
30
25
20
15
10
5
Warfarin
triple therapy
Dabigatran 110 mg
dual therapy
HR: 0.52 (95% CI: 0.42–0.63)
Non-inferiority P<0.001
P<0.001
0 90 180 270 360 450 540 630 720
Time to first event (days)
40
35
30
25
20
15
10
5
0
Dabigatran 150 mg
dual therapy
Warfarin
triple therapy
HR: 0.72 (95% CI: 0.58–0.88)
Non-inferiority P<0.001
P=0.002
2,725 NVAF patients post-CS: warfarin+ASA vs Dabigatran 110 mg BID vs 150 mg BID (all P2Y12 inhibitor).
Primary end point: major or clinically relevant nonmajor bleeding event.
RE-DUAL PCI trial
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
10. No significant differences in efficacy end-points among 3 groups
Composite efficacy end point:
Death, thromboembolic events (MI, stroke, or systemic embolism), or unplanned revascularization.
Cannon et al. N Engl J Med. 2017 Oct 19;377(16):1513-1524.
RE-DUAL PCI trial
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
11. PIONEER-AF trial
2,124 NVAF patients undergoing CS
Group 1: Riva 15 mg + P2Y12
Group 2: Riva 2.5 mg b.i.d. + DAPT followed by Riva 15 mg + P2Y12
Group 3: VKA + DAPT
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
12. My concern with low-dose NOAC: stent thrombosis (trials
unpowered)
RE-DUAL PCI PIONEER AF
≈ 11% of patients
included had
STEMI
≈ 12% of patients
included had
STEMI
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
13. AUGUSTUS trial
ACS PCI
37.3%23.9% 38.8%
76.1%61.2%
• 4,614 patients with AF after ACS and/or PCI.
• 6-month follow-up (!)
2x2 randomization
• Apixaban (standard dose) vs VKA.
• ASA 81 mg/d vs placebo
(in association with any P2Y12 inhibitor ≥ 6
mo).
Primary end-point: major or clinically relevant bleeding through 6 months.
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
14. 10.5
%
14.7%
9.0%
16.1%
Major or CRNMB: Apixaban vs VKA. Major or CRNMB: ASA vs placebo.
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
AUGUSTUS trial
15. ENTRUST-AF
• 1,506 patients with AF after PCI-stent.
• Randomization (1:1 design) to: Edoxaban + P2Y12 inhibitor or vKA + ASA 100 mg/d + P2Y12 inhibitor.
• Primary end-point: major or clinically relevant non-major bleeding at 12 months.
17.0% (20.7% annualized)
20.0% (25.6% annualised)
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
16. Figure S6. Kaplan-Meier curve for the main efficacy endpoint, ITT analysis
0·10
0·09
0·08
0·07
0·06
0·05
0·04
0·03
0·02
0·01
0·00
0 30 60 90 120 150 180 210 240 270 300 330 360
Days from randomisation
EDOXABAN
Number at risk:
751 719 705 695 685 679 670 664 657 652 643 639 575
VKA 755 718 700 690 678 667 661 657 653 646 640 635 575
Edoxaban VKA
Number of events:
Edoxaban: 49/751
VKA: 46/755
HR (95% CI): 1·06 (0·71; 1·69)
Cumulativeincidenceinoutcomes
Main efficacy outcome
(CV death, stroke, systemic embolic events, MI, and definite stent thrombosis)
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
ENTRUST-AF
17. Timing and bleedings
Hypothesis: investigators were concerned
about bleeding risk with VKA and
undertreated these patients
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
ENTRUST-AF
18. 4,510 out of 21,105 patients (21.4%) had previous CAD.
4,5
3,2
3,6
2,5
Prior CAD No prior CAD
VKA Edoxaban 60
Major bleeding (annualized rate).
Putting into context the ENTRUST: CAD patients in the ENGAGE
ARR: 0.9%
RRR: 20%
ARR: 0.7%
RRR: 22%
1,2 1,2
0,7 0,6
Prior CAD No prior CAD
VKA Edoxaban 60
Fatal or life-threatening bleeding
ARR: 0.5%
RRR: 42%
ARR: 0.6%
RRR: 50%
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
19. 4,510 out of 21,105 patients (21.4%) had previous CAD.
5,4
3,2
4,4
2,6
Prior revasc No prior revasc
VKA Edoxaban 60
Major bleeding (annualized rate).
ARR: 1,0%
RRR: 19%
ARR: 0.6%
RRR: 19%
1,4
1,1
0,9
0,6
Prior revasc No prior revasc
VKA Edoxaban 60
Fatal or life-threatening bleeding
ARR: 0.5%
RRR: 36%
ARR: 0.5%
RRR: 45%
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
Putting into context the ENTRUST: CAD patients in the ENGAGE
20. Putting into context the ENTRUST: concomitant use of SAPT
in the ENGAGE
NOAC in AF patients after coronary stenting Dr. Raúl Moreno
22. CONCLUSIONS
• With the ENTRUST trial, the puzzle of NOAC in patients with AF and PCI-
stent is completed.
• In ENTRUST, edoxaban was not inferior to VKA in terms of bleeding
complications, with similar rate of cardiac events.
• The risk reduction in bleeding, although not statistically significant, was
consistent with the benefit observed in other edoxaban trials.
• Edoxaban is now an alternative to other NOAC in patients treated with
PCI-stent and AF.
NOAC in AF patients after coronary stenting Dr. Raúl Moreno