REVIEW ARTICLES International Journal of Arrhythmia 2016;17(1):51-55 doi: 수술전후항응고요법 ( 백내장수술, 치과및위장관내시경시

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REVIEW ARTICLES doi: http://dx.doi.org/10.18501/arrhythmia.2016.

1 REVIEW ARTICLES doi: ( 백내장수술, 치과및위장관내시경시술 ) 정중화 조선대학교의과대학내과학교실 Joong-Wha Chung, MD Peri-procedural Management of Anticoagulation Therapy (cataract eye surgery, dental procedure and gastrointestinal endoscopy) Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea Received: November 16, 2015 Revision Received: February 11, 2016 Accepted: March 28, 2016 Correspondence: Joong-Wha Chung, MD Department of Internal Medicine, College of Medicine, Chosun University, 365, Pilmun-daero, Dong-gu, Gwangju, Republic of Korea Tel: Fax: chungjoongwha@gmail.com Copyright 2016 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd. ABSTRACT Anticoagulation therapy is widely used to prevent thromboembolism in patients with atrial fibrillation, venous thromboembolism, and mechanical heart valves. The temporary interruption of anticoagulants is common to reduce the bleeding risk during peri-procedures. Traditionally, warfarin was held for several days before procedures with heparin bridging therapy. However, recent data showed that stopping warfarin was not necessary before procedures with a low bleeding risk, such as a gastrointestinal endoscopy, cataract eye surgery, and dental procedures when the thromboembolic risk of the patient is moderate-to-high. This review article outlines the estimation of the thromboembolic and bleeding risk before procedures, and determines the timing of anticoagulant interruption. Key Words: Anticoagulants Procedures Cataract Tooth Extraction Endoscopy 서론 장기적인항응고요법이필요한경우의 1/3 정도에서항응고요법을중단해야하는경우가발생하는데, 위장관내시경검사와치과시술이대부분을차지한다. 1 만약항응고요법을중단하게되면혈전색전증의위험이증가하는반면에항응고요법을유지하면출혈의위험이증가하게된다. 따라서환자마다의특성을고려하여시 ( 수 ) 술과관련된항응고요법을결정해야한다. 미국흉부학회 (ACCP) 의지침 (guideline) 에의하면시 ( 수 ) 술예정일기준으로최소일주일전에는환자에대한평가가이뤄져야하며, 2 시 ( 수 ) 술과관련된항응고요법을결정하는데다음과같은여러가지사항들을고려해야한다. 출혈합병증의위험정도 유럽부정맥학회 (EHRA) 의치료권고안에의하면출혈합병증의위험정도는대부분시 ( 수 ) 술의종류에따라 51

2 결정되지만 (Table 1) 3, 신장기능과같은환자의특성 (HAS- BLED 점수 ) 도중요하게고려해야한다. 4 과거의지침들은심장박동조율기 (cardiac pacemaker) 나삽입형제세동기 (implantable cardioverter defibrillator, ICD) 와같은시술을고출혈위험군으로분류하였으나, 최근연구에의하면 warfarin 중단후 heparin을사용한가교치료 (bridging therapy) 군보다 warfarin을지속한군에서출혈의위험성이낮았으며, 두군간의혈전색전증발생에는차이가없었다. 5 치아발치를 1 3개시행하는치과시술은저위험군으로분류되어있기때문에항응고제를유지하면된다. 심방세동과관련된폐정맥분리술과같은전극도자절제술 (catheter ablation) 의경우 warfarin을유지하는것이 heparin 가교치료에비해혈전색전증과출혈의위험을감소시켰다고한다. 6 미국내시경학회의지침에따르면점막생검을포함하는위장관 / 대장내시경검사는항응고제중단없이도안전하게시행될수있는시술로정의하였지만, 용종절제술 (polypectomy) 은출혈의위험이높은시술로정의하고있다. 7 혈전색전증의위험정도 혈전색전증의위험도를평가할때중요한점은심방세동환자의 CHA 2 DS 2 점수와기계심장판막 (mechanical heart valve) 의종류, 그리고정맥혈전색전증 (venous thromboembolism, VTE) 의발생시기이다 (Table 2). 8 Table 1. Procedural bleeding risks Bleeding risk* Major risk Minor risk Minimal risk Procedure and Surgery Any major operation Liver biopsy Kidney biopsy ESWL Transurethral prostate biopsy Spinal or epidural anesthesia Catheter ablation of simple left-sided supraventricular tachycardia Endoscopy with biopsy Prostate or bladder biopsy Electrophysiologic study or catheter ablation for right-sided supraventricular tachycardia Non-coronary angiography Pacemaker or ICD implantation Dental interventions Extraction of one to three teeth Paradontal surgery Incision of abscess Implant positioning Cataract or glaucoma intervention Endoscopy without surgery Modified from Heidbuchel H, et al. Europace. 2015;17: ESWL, extracorporeal shockwave lithotripsy; ICD, implantable cardioverter defibrillator. Table 2. Risk stratification for peri-procedural thromboembolism Thromboembolic risk (annual risk) Atrial fibrillation (CHADS 2 ) Mechanical heart valve Venous thromboembolism High (>10%) 5 6 Moderate (5-10%) 3 4 Low (<5%) 0-2 Mitral valve prosthesis Cage-ball or tilting disc aortic valve prosthesis Bileaflet aortic valve prosthesis with >1 risk Atrial fibrillation Previous stroke or TIA Hypertension Diabetes mellitus Congestive heart failure Age over 75 years Bileaflet aortic valve prosthesis without atrial fibrillation Recent (within 3 months) VTE event VTE within the past 3-12 months VTE >12 months previous TIA, transient ischemic attack; VTE, venous thromboembolism. Modified from Daniels PR. BMJ. 2015;351:h

3 Table 3. Discontinuation of NOACs NOAC Low bleeding risk procedure High bleeding risk procedure Creatinine clearance (ml/min) Dabigatran 24h 48h 80 36h 72h h 96h Not indicated Not indicated Not indicated <15 Apixaban /Rivaroxaban /Edoxaban 24h 48h >30 36h 48h Not indicated <15 NOAC, novel or non-vitamin K antagonist oral anticoagulant. Modified from Heidbuchel H, et al. Europace. 2015;17: 심방세동의경우 CHA 2 DS 2 점수가높거나최근 3개월내에심방세동으로인한뇌졸중이나일과성뇌허혈이있었으면중등도이상의위험군으로분류할수있다. 미국심장학회 / 미국심장협회 (ACC/AHA) 지침을보면혈전색전증의위험도가낮거나동리듬 (sinus rhythm) 으로유지가잘되는심방세동에서는시술 5일전에 warfarin을중단하고가교치료를하지않아도된다. 9 기계심장판막의경우인공승모판막이대동맥인공판막에비해 caged ball이이엽 (bileaflet) 기계판막에비해혈전색전증의위험이높다. 10 시행하는것이좋다. 하루두번복용하는 NOAC은마지막약을복용한후 12시간, 하루한번복용하는 NOAC은복용후 24시간에시 ( 수 ) 술하면된다. 약제마다의중단시점은 Table 3에정리하였다. 3 시 ( 수 ) 술이끝나고출혈이안정화되면 warfarin은 24시간이내에시작하고 NOAC의경우에는 6 8 시간후에재투여하는데, 시 ( 수 ) 술의출혈위험도가높으면 48 72시간뒤에사용한다. 3,12 항응고제가교치료 시 ( 수 ) 술전항응고제의중단시점과재사용시점 시 ( 수 ) 술전에항응고제를중단해야한다면항응고제의종류, 시 ( 수 ) 술과관련된출혈위험도, 그리고새로운경구용항응고제 (novel or non-vitamin K antagonist oral anticoagulant, NOAC) 의경우에는크레아티닌청소율을고려해야한다. Warfarin은시 ( 수 ) 술 5일전부터중단하면되는데, INR (international normalized ratio) 이 2.5 이상으로유지되었거나고령환자에서는 5일이상중단해야할수도있어 INR 검사결과를참조해야한다. 11 NOAC을사용하고있다면약제를중단하지않아도되는시 ( 수 ) 술의경우에는약제의혈중농도가최저치 (trough level) 일때 85% 이상에서 CHADS 2 점수가 1 3점인심방세동환자를대상으로 heparin 가교치료의유용성을관찰한 BRIDGE 연구 (Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery study) 를살펴보면 warfarin을중단하고가교치료를시행한군과시행하지않은군사이에혈전색전증의발생은통계적으로차이가없었고, 오히려가교치료를시행한군에서주요출혈 (major bleeding) 의위험이증가하였다. 13 이러한결과는 warfarin을중단했을때발생한다고알려져있는반응성과응고 (rebound effect) 에의한것으로생각된다. 14 Rivaroxaban을포함한 NOAC의연구결과를살펴보면시 ( 수 ) 술전약제를중단하고 53

4 가교치료를하지않아도안전해보인다. 1,15,16 전향적관찰연구를보더라도 NOAC을사용하는경우에가교치료를시행한군에서주요출혈의발생이 5배나증가하였다. 1 결론 Warfarin의오래된역사에도불구하고 NOAC의처방은빠르게증가하고있으며계속해서신약들이등장하고있다. Warfarin을사용하는경우과거에비해 heparin 가교치료의유용성이감소하는경향이지만, 혈전색전증의위험이높으면반드시시행해야한다. NOAC의경우에는항응고효과를비교적정확하게예측할수있기때문에대부분의경우에 heparin 가교치료가필요하지않다. 위장관내시경검사와치과시술과같은상당수의임상시 ( 수 ) 술과관련된출혈위험성은낮기때문에환자가가지고있는혈전색전증의발생위험이중등도이상이아니면충분한기간동안항응고제를중단한후안전하게시 ( 수 ) 술할수있을것으로생각된다. References 1) Beyer-Westendorf J, Gelbricht V, Förster K, Ebertz F, Köhler C, Werth S, Kuhlisch E, Stange T, Thieme C, Daschkow K, Weiss N. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur Heart J. 2014;35: ) Douketis JD, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, Dunn AS, Kunz R; American College of Chest Physicians. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e326S-350S. 3) Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with nonvalvular atrial fibrillation. Europace. 2015;17: ) Omran H, Bauersachs R, Rübrenacker S, Goss F, Hammerstingl C. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bridging REgistRy (BORDER). Thromb Haemost. 2012;108: ) Birnie DH, Healey JS, Wells GA, Verma A, Tang AS, Krahn AD, Simpson CS, Ayala-Paredes F, Coutu B, Leiria TL, Essebag V; BRUISE CONTROL Investigators. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013;368: ) Di Biase L, Burkhardt JD, Santangeli P, Mohanty P, Sanchez JE, Horton R, Gallinghouse GJ, Themistoclakis S, Rossillo A, Lakkireddy D, Reddy M, Hao S, Hongo R, Beheiry S, Zagrodzky J, Rong B, Mohanty S, Elayi CS, Forleo G, Pelargonio G, Narducci ML, Dello Russo A, Casella M, Fassini G, Tondo C, Schweikert RA, Natale A. Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial. Circulation. 2014;129: ) Eisen GM, Baron TH, Dominitz JA, Faigel DO, Goldstein JL, Johanson JF, Mallery JS, Raddawi HM, Vargo JJ 2nd, Waring JP, Fanelli RD, Wheeler-Harbough J; American Society for Gastrointestinal Endoscopy. Guideline on the management of anticoagulation and antiplatelet therapy for endoscopic procedures. Gastrointest Endosc. 2002;55: ) Daniels PR. Peri-procedural management of patients taking oral anticoagulants. BMJ. 2015;351:h ) January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; ACC/AHA Task Force Members AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130: ) Cannegieter SC, Rosendaal FR, Briët E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89: ) Hylek EM, Regan S, Go AS, Hughes RA, Singer DE, Skates SJ. Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Ann Intern Med. 2001;135: ) Spyropoulos AC, Douketis JD. How I treat anticoagulated 54

5 patients undergoing an elective procedure or surgery. Blood. 2012;120: ) Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, Garcia DA, Jacobson A, Jaffer AK, Kong DF, Schulman S, Turpie AG, Hasselblad V, Ortel TL; BRIDGE Investigators. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373: ) Genewein U, Haeberli A, Straub PW, Beer JH. Rebound after cessation of oral anticoagulant therapy: the biochemical evidence. Br J Haematol. 1996;92: ) Sherwood MW, Douketis JD, Patel MR, Piccini JP, Hellkamp AS, Lokhnygina Y, Spyropoulos AC, Hankey GJ, Singer DE, Nessel CC, Mahaffey KW, Fox KA, Califf RM, Becker RC; ROCKET AF Investigators. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation. 2014;129: ) Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchel H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M; RE-LY Investigators. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long- Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation. 2012;126:

종설 ISSN 일산병원학술지 2017;16(2):57-66 비판막성심방세동환자에서의항응고치료의최신요법 국민건강보험일산병원심장내과 양주영 Current Antithrombotic Therapy for Patients with Nonvalvular Atr

종설 ISSN 일산병원학술지 2017;16(2):57-66 비판막성심방세동환자에서의항응고치료의최신요법 국민건강보험일산병원심장내과 양주영 Current Antithrombotic Therapy for Patients with Nonvalvular Atr 종설 ISSN 2093-9272 일산병원학술지 207;6(2):57-66 비판막성심방세동환자에서의항응고치료의최신요법 국민건강보험일산병원심장내과 양주영 Current Antithrombotic Therapy for Patients with Nonvalvular Atrial Fibrillation Joo Young Yang Department of Internal