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Braveheart. NOAC in AF patients after coronary stenting

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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. 1. NOAC in AF patients after coronary stenting Dr. Raúl Moreno Hospital La Paz - Madrid, Spain BRAVEHEART Fotoretiradadelapelícula“Braveheart”utilizadaparafineseducativos segúnelart32delaLPI.
  2. 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. 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. 4. BRAVEHEART NOAC in AF patients after coronary stenting Dr. Raúl Moreno Hospital La Paz - Madrid, Spain Fotoretiradadelapelícula“Braveheart”utilizadaparafineseducativos segúnelart32delaLPI.
  5. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 20. Putting into context the ENTRUST: concomitant use of SAPT in the ENGAGE NOAC in AF patients after coronary stenting Dr. Raúl Moreno
  21. 21. SAGE Open Medicine SAGEOpen Medicine 3: 2050312115613350 © The Author(s) 2015 Reprintsand permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2050312115613350 smo.sagepub.com Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versusother nonvitamin K antagonist oral anticoagulantsamong patientswith nonvalvular atrial fibrillation and CHADS2 score⩾ 2 Maria M Fernandez1, Jianmin W ang1, Xin Ye2, W inghan Jacqueline Kwong2, Bintu Sherif1, Susan Hogue1 and Beth Sherrill1 Abstract Background: The nonvitamin K antagonist oral anticoagulants pivotal clinical trialsfor stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient characteristics. Objective: We sought to evaluate the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants in the management of stroke prevention in atrial fibrillation by adjusting for differences in baseline stroke risk and the length of follow-up amongthe four phase 3 randomized controlled trials. Methods: We conducted a systematic literature review of randomized controlled trials evaluating the nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation and performed a network meta-analysis using data from ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and ARISTOTLE, with warfarin as a common comparator. To adjust for between-trial differences in CHADS2 score and length of follow-up, annualized event rates among patients with CHADS2 score⩾ 2 were analyzed usingamixed Poisson’s regression model. Results: Once-daily high-dose edoxaban was associated with significant lower major bleeding episodes compared with once- daily rivaroxaban (risk ratio, 0.76; 95% confidence interval, 0.66–0.89), twice-daily dabigatran 150mg (risk ratio, 0.78; 95% confidence interval, 0.61–0.84), and twice-daily dabigatran 110mg (risk ratio, 0.83; 95% confidence interval, 0.71–0.98) and similar bleedingrisk compared with twice-daily apixaban (risk ratio, 1.08; 95%confidence interval, 0.91–1.28). Risk of stroke and systemic embolism wassimilar for the high-dose edoxaban and other nonvitamin K antagonist oral anticoagulant regimens. The low-dose edoxaban regimen was associated with asignificant lower risk of major bleedingthan other nonvitamin K antagonist oral anticoagulantsand asignificant higher risk of stroke and systemic embolism compared with apixaban and dabigatran 150mg. 613350SMO0010.1177/20503121 15613350 SAGE Open Medicine Fernandez et al. h-article 2015 Original Article • Four phase 3 pivotal trials for stroke prevention in AF (RE- LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48). • Network meta-analysis including only data from patients with CHADS2 score⩾2 in RE-LY and ARISTOTLE. Major bleeding Stroke and systemic embolism Putting into context the ENTRUST NOAC in AF patients after coronary stenting Dr. Raúl Moreno
  22. 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

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