Special Conditions of NOAC PCI 가톨릭의대 순환기내과 장성원

Transcription

1 Special Conditions of NOAC PCI 가톨릭의대 순환기내과 장성원

2 Issues on Patients with NOAC PCI Peri-procedural management CKD or dialysis Cardioversion Neurological situations

3 Dual Antiplatelet Therapy with Oral Anticoagulants PCI IN ATRIAL FIBRILLATION

4 Sites of action: OAC and DAPT Circ Cardiovasc Interv 2016;9:e004395

5 Dual Antiplatelet Therapy in PCI Primary end point: death, revascularization, stent thrombosis, MI Leon et al. N Engl J Med 1988;339:1665

6 ACTIVE-W DAPT vs. OAC in AF Primary end point: stroke, non-cns systemic embolism, MI, vascular death ACTIVE investigators. Lancet 2006;367;1903

7 Patients with AF undergoing PCI OAC Triple? DAPT

8 Randomized trial with VKA WOEST trial ISAR-TRIPLE trial

9 WOEST trial: Primary end point Triple: ASA+CLOPD+warfarin Double: CLOPD+warfarin

10 WOEST trial: Secondary end point

11 Limitations Small number of events Open-label design Low PPI use Majority of femoral access High (70%) prevalence of stable CAD Relatively simple lesions intervened Limited power to detect stent thrombosis

12 ISAR-TRIPLE trial 6 weeks vs. 6 month CLOPD therapy Triple therapy as short as possible

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15 기타 registry 연구를종합하면 VKA+DAPT 는 VKA+SAPT 보다 bleeding risk 가높다. VKA+SAPT 는 VKA 보다 bleeding risk 가높다. CLOPD+VKA 는 ASA+VKA 보다 bleeding risk 가높다. Efficacy 에대해서는일관된결과가없다.

16 NOACs in Phase III Trials Dabigatran Higher rate of MI vs. VKA (OR 1.33, CI ) in a metaanalysis Uchino et al. Arch Intern Med 2012;172:397 No excess of MI in a Danish and an US Medicare registry Larsen et al. J Am Coll Cardiol 2013;61:2264, US FDA DSC Rivaroxaban An excess of MI vs. VKA (no stat significance) Patel et al N Engl J Med 2011;365:883 Edoxaban An excess of MI vs. VKA (no stat significance) Giugliano et al N Engl J Med 2013;369:2093

17 NOACs in Patients with ACS Apixaban DAPT+apixaban (standard dose) increased major and fatal bleeding without clear benefit of ischemic events. Alexander et al. N Engl J Med 2011;365:699 Very low dose rivaroxaban (2.5mg bid) DAPT 에추가하였을때 ACS outcome 은좋았으나, bleeding 은역시증가. 저용량에서는뇌졸중예방효과는없음. Mega et al. N Engl J Med 2012;366:9 Taken together, triple therapy should be kept as short as possible.

18 Current Guideline 2015 EHRA practical guide on NOAC

19 2015 EHRA practical guide on NOAC

20 On-Going Trial RE-DUAL PCI (Dabigatran) Finished PIONEER AF PCI (Rivaroxaban) Finished and published AUGUSTUS (Apixaban) ENTRUST-AF PCI (Edoxaban)

21 Gibson et al. N Engl J Med 2016;375:2423

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23 RIVA + CLOPD RIVA + ASA/CLOPD Warfarin + ASA/CLOPD

24 Gibson et al. N Engl J Med 2016;375:2423

25 Gibson et al. N Engl J Med 2016;375:2423

26 Primary Safety Endpoint Gibson et al. N Engl J Med 2016;375:2423

27 Secondary Efficacy Endpoint Gibson et al. N Engl J Med 2016;375:2423

28 Supplementary Appendix

29 Limitations Efficacy 를증명하기에는대상환자가적다. Superiority 를증명하기위해서는각군당 13,598 명이필요 하물며 1, 6, 12 개월사용군간의 subgroup analysis 는통계적분석력이더떨어진다. Ticagrelor, prasugrel 사용군이적다.

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31 AUGUSTUS Trial: NVAF Patients Undergoing PCI Phase IV, open-label, 2 x 2 factorial, randomized controlled clinical trial SELECT INCLUSION CRITERIA NVAF Age years Physician decision that oral anticoagulant is indicated ACS or PCI within prior 14 days with planned P2Y12 inhibitor for 6 months RANDOMIZE N=4,600 SELECT EXCLUSION CRITERIA Contraindication to dual-antiplatelet therapy (DAPT) Other reason for VKA (e.g. prosthetic valve, mod/severe mitral stenosis) CABG APIXABAN 5 mg PO BID 2.5 mg BID in select patients P2Y12 inhibitor for all patients x 6 months Aspirin for all on the day of ACS or PCI Aspirin versus placebo after randomization VKA Target INR 2-3 Aspirin 81 mg Daily PLACEBO Aspirin 81 mg Daily PLACEBO Primary Endpoint: ISTH major bleeding or clinically relevant non -major bleeding Seconday Endpoint: Composite (death, stroke, MI, stent thrombosis, urgent revsacularization); first rehospitalization CABG, coronary artery bypass graft; ** Patients with 2 of the following: age 80 years, weight 60 kg, serum creatinine 1.5 mg/ dl (133 mm) Source: Clinicaltrials.gov identifier: NCT ; EUDRACT: ; Date accessed February 7, 2016.

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33 기타고려사항 시술전평가 PCI 가꼭필요한가? Ischemic/thrombotic and bleeding risk 시술시고려사항 Vascular access (radial) Stent selection (new-generation DES) 시술후고려사항 Re-assessment of risk profile Recommend PPI and avoid NSAIDs

34 Uninterrupted OAC for Ablation in Atrial Fibrillation PERIPROCEDURAL MANAGEMENT

35 Calkins et al. N Engl J Med 2017 online

36 Calkins et al. N Engl J Med 2017 online

37 Time to First Adjudicated Major Bleeding Events Calkins et al. N Engl J Med 2017 online

38 Adverse Events Calkins et al. N Engl J Med 2017 online

39 Catheter ablation Catheter ablation VENTURE AF Design: Randomized, Open-label, Active-controlled Multicentre Study Rivaroxaban 20 mg od Rivaroxaban 20 mg od Population: Patients with paroxysmal, persistent or long-standing persistent NVAF, scheduled for catheter ablation Planned TEE or ICE a Sufficient anticoagulation b Insufficient anticoagulation c R 124 1:1 N=248 R days 30±5 days VKA (INR ) VKA (INR ) Rivaroxaban 20 mg od Rivaroxaban 20 mg od 4 5 weeks 30±5 days 1:1 VKA (INR ) VKA (INR ) End of treatment a Immediate TEE or ICE confirming the absence of detectable intracardiac thrombus b Sufficient anticoagulation documented for 3 weeks prior to randomization c These patients were randomized to receive study drug for 4-5 weeks prior to the procedure Heparin iv ACT sec (target sec) Please refer to the slide notes for the full details of the footnotes Naccarelli GV et al, J Interv Card Electrophysiol 2014;41:

40 VENTURE AF: Complications During the Study Period Rivaroxaban VKA Total Any adjudicated event n=123 n=121 N=244 Any bleeding event* Major bleeding event Vascular pseudoaneurysm Non-major bleeding event Most relevant: Arteriovenous fistula Catheter/puncture site haemorrhage Haematoma/vessel puncture site haematoma Vascular pseudoaneurysm n=124 n=124 N=248 Any thromboembolic events (composite) # Ischaemic stroke Vascular death n=114 n=107 N=221 Any other procedure-attributable event Pericardial effusion without tamponade *safety population; # ITT population; per-protocol population For full list see publication or back-up-slide Adapted from Cappato R et al. Eur Heart J 2015; doi: /eurheartj/ehv177 [E-Pub ahead of print] 41

41 Catheter ablation Follow-up 90 days AXAFA Trial: NVAF Patients Undergoing Catheter Ablation Phase IV, Prospective Parallel Group, Randomized, Open-label, Blind Assessment Noninferiority Study (PROBE)* Select Inclusion Criteria (n= 650) NVAF with clinical indication for catheter ablation Age 18 years old CHADS 2 1 R Randomisation stratified by type of AF Apixaban 5 mg twice daily 2.5 mg twice daily in select patients** Minimum 30 days of therapy VKA therapy (target INR 2-3) Minimum 30 days of therapy Primary endpoint All-cause death, stroke, major bleeding Substudy Silent brain lesions on MRI within 48 hours after ablation Countries: Belgium, Denmark, Germany, Italy, Netherlands, Spain, UK, US ** Patients with 2 of the following: age 80 years, weight 60 kg, serum creatinine 1.5 mg/ dl (133 mm) INR, international normalised ratio Study number NCT Details available from

42 Catheter ablation Follow-up 30 days AEIOU: NVAF Patients Undergoing Catheter Ablation Phase IV, open label, randomized, parallel assignment trial with prospective and retrospective cohorts* Select Inclusion Criteria (n= 360) NVAF with clinical indication for catheter ablation Age 18 years old R Randomisation stratified by site Interrupted: HOLD AM dose prior to procedure Uninterrupted: Administer AM Dose Prior to Procedure Apixaban 5 mg twice daily X 21 Days 2.5 mg twice daily in select patients** Primary endpoint Clinically significant bleeding (BARC 2) Thrombotic events: composite non-hemorrhagic stroke and systemic thromboembolic events ** Patients with 2 of the following: age 80 years, weight 60 kg, serum creatinine 1.5 mg/ dl (133 mm) INR, international normalised ratio Study number N C T Details available from Retrospective Warfarin Cohort September 1, present

43 Summary PCI in AF patients NOAC (or VKA) 는 stroke risk stratification 에따라평생사용한다. DAPT 의기간을조절한다. VKA 를사용할경우 INR NOAC 의경우 lowest therapeutic dose P2Y12 inhibitor 로는 clopidogrel 을선호 ASA 는 mg/d Uninterrupted OAC in AF ablation NOAC 에서도통용될가능성이높다 Antidote 가있을경우유리할것