Marco Aurélio Fraga Borges Neurologista

Agosto, 2015

JACC March 17, 2015

Circulation. 2014;130:e191-e193

e191

Anticoagulants (commonly called

blood thinners) are medications that

interact with the body’s natural blood-

clotting system to treat and prevent

abnormal blood clots. Anticoagulants are

used in patients who have blood clots in

the legs (called deep vein thrombosis or

DVT) or in the lungs (called pulmonary

embolism or PE), other types of blood

clots in the arteries or veins, an irregular

heart rhythm called atrial fibrillation that

increases the risk of stroke, and mechan-

ical heart valves. For decades, warfarin

(also known as Coumadin) was the pri-

mary anticoagulant used. Recently, sev-

eral other medications known as novel

oral anticoagulants (NOACs) have been

studied and released on the market as

alternatives to warfarin. Given the num-

ber of choices now available for patients

who need anticoagulants, the benefits,

risks, side effects, and convenience of

each anticoagulant must be carefully

considered.

How Do NOACs Differ From Warfarin?

Warfarin treats and prevents blood

clots by decreasing the production of

several clotting proteins that rely on

vitamin K. Warfarin is taken by mouth

once daily, and the dose varies depend-

ing on inherited factors, reason for the

medication, and diet (Table 1). Because

of the variations in doses needed for

each patient, warfarin requires frequent

laboratory monitoring and dose adjust-

ment to maintain blood levels within

the target range (called the international

normalized ratio or INR). Below target

blood levels, patients have an increased

risk of clotting. Above target blood lev-

els, the risk of bleeding increases. As

with all anticoagulants, warfarin use

increases the risk of bleeding. If this

happens, vitamin K or various blood

products can be given to replace the

clotting factors affected by warfarin.

NOACs work by targeting individual

clotting proteins. They do not require

laboratory monitoring or dose adjust-

ment because they reach predictable

levels in most patients (Table 1). They

are also shorter-acting than warfarin. If

a dose of warfarin is missed, a patient’s

blood may still be adequately thinned

because it takes several days for the

anticoagulant effect to wear off. In con-

trast, if a dose of a NOAC is missed,

patients quickly lose the anticoagulant

effect and are unprotected from blood

clots. Unlike warfarin, no specific anti-

dotes are currently available to reverse

the blood-thinning effect of NOACs

in patients who are bleeding. Because

its anticoagulant effect lasts for days,

warfarin must be stopped several days

before surgery and certain other proce-

dures. During interruption of warfarin

treatment, patients may need to give

themselves injections with shorter-act-

ing anticoagulants or be admitted to the

hospital for intravenous anticoagulants

to prevent blood clots (often called

bridging). The NOACs rarely require

bridging because they are shorter act-

ing and can be safely stopped a day or

two before surgery or procedures.

NOACs are taken once or twice daily

(depending on the NOAC being used and

the condition being treated). Although

NOACs have been evaluated for stroke

prevention in atrial fibrillation and treat-

ment and prevention of DVTs and PEs,

they are contraindicated for treatment in

patients with mechanical heart valves.

WarfarinWarfarin has been used for decades to

treat patients with atrial fibrillation,

(Circulation. 2014;130:e191-e193.)© 2014 American Heart Association, Inc.

Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.114.010426

The information contained in this Circulation Cardiology Patient Page is not a substitute for medical advice, and the American Heart Association recommends consultation with your doctor or healthcare professional.

From the Cardiovascular Division (G.P.) and Department of Medicine (R.K.W., C.E.R.), Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

Correspondence to Gregory Piazza, MD, MS, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail gpiazza@partners.org

Warfarin Versus Novel Oral AnticoagulantsHow to Choose?

Rishi K. Wadhera, MD, MPhil; Cori E. Russell, MD; Gregory Piazza, MD, MS

CARDIOLOGY PATIENT PAGE

by guest on August 17, 2015http://circ.ahajournals.org/Downloaded from

1960 1970 1980 1940 2010 1950 1990 2000

1940s HNF comercialmente disponível

1954 Varfarina

comercialmente disponível

1993 Primeira HBPM

comercialmente disponível

1998 Primeiro IDT comercialmente disponível

2001 Primeiro inibidor sintético de Xa comercialmente disponível

~50 anos

2008 - Dabigatrana 2009 - Xarelto Aprovados para uso clínico EMEA e ANVISA

AC=anticoagulante; IDT=inibidor direto de trombina; FDA=Food and Drug Administration; HBPM=heparina de baixo peso molecular; HNF=heparina não fracionada

Journal of Thrombosis and Haemostasis 2013, 11: 177–179

Escolher o indivíduo ADEQUADO para ser anticoagulado na intensidade ADEQUADA com

a droga ADEQUADA.

J Am Coll Cardiol. 2014;64(21):2246-2280

RECOMENDAÇÕES CLASSE I

RECOMENDAÇÕES CLASSE III

Stroke. 2014;45:2160-2236 Lancet. 2009 Oct 10;374(9697):1271-83

Insuficiência coronariana

FIBRILAÇÃO

ATRIAL

SÍNDROME CORONARIANA

AGUDA

DOENÇA CORONARIANA

ESTÁVEL

Europace (2013) 15, 625–651 Europace (2014) 16, 293–298

ANGIOPLASTIA CORONARIANA

RISCO DE EVENTO CARDIOEMBÓLICO

RISCO ATEROTROMBÓTICO

RISCO DE SANGRAMENTO

Lancet. 2009 Oct 10;374(9697):1271-83 Europace (2013) 15, 625–651

Lancet. 2013 Mar 30;381(9872):1107-15 J Am Coll Cardiol. 2014;64(21):2246-2280

Lancet. 2013 Mar 30;381(9872):1107-15 J Am Coll Cardiol. 2014;64(21):2246-2280

Europace (2013) 15, 625–651

EHRA PRACTICAL GUIDE

European Heart Rhythm Associat ion Pract ical

Guide on the use of new oral ant icoagulants in

pat ients with non-valvular atr ial fibrillat ion

Hein Heidbuchel 1*, Peter Verhamme1, Marco Alings2, Mat thias Antz3,

W erner Hacke4, Jonas Oldgren5, Peter Sinnaeve1, A. John Camm 6,

and Paulus Kirchhof7,8

1Department of Cardiovascular Medicine, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium; 2Department of Cardiology, Amphia Ziekenhuis, Breda,

Netherlands; 3Department of Cardiology, Klinikum Oldenburg, Oldenburg, Germany; 4Department of Neurology, Ruprecht Karls Universitat, Heidelberg, Germany; 5Uppsala

Clinical Research Center and Dept of Medical Sciences, Uppsala University, Uppsala, Sweden; 6Clinical Cardiology, St George’s University, London, UK; 7University of Birmingham

Centre for Cardiovascular Sciences, Birmingham, UK; and 8Department of Cardiology and Angiology, University of Munster, Germany

Received 7 November 2012; accepted after revision 18 March 2013

New oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial

fibrillation (AF). Both physiciansand patientswill have to learn how to use these drugseffectively and safely in clinical practice. Many unresolved

questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to co-

ordinate aunified way of informingphysicianson the use of the different NOACs. A writinggroup listed 15 topicsof concrete clinical scenarios

and formulated as practical answers as possible based on available evidence. The 15 topics are: (1) Practical start-up and follow-up scheme for

patientson NOACs; (2) How to measure the anticoagulant effect of NOACs; (3) Drug–druginteractionsand pharmacokineticsof NOACs; (4)

Switching between anticoagulant regimens; (5) Ensuring compliance of NOAC intake; (6) How to deal with dosing errors; (7) Patients with

chronic kidney disease; (8) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?

(9) Management of bleeding complications; (10) Patients undergoing a planned surgical intervention or ablation; (11) Patients undergoing an

urgent surgical intervention; (12) Patients with AF and coronary artery disease; (13) Cardioversion in a NOAC-treated patient; (14) Patients

presenting with acute stroke while on NOACs; (15) NOACs vs. VKAs in AF patients with a malignancy. Since new information is becoming

available at a rapid pace, an EHRA Web site with the latest updated information accompanies this text (www.NOACforAF.eu).- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywor ds Atrial fibrillation † Anticoagulation † Stroke † Bleeding † Pharmacology

Int roduct ion

New oral anticoagulants (NOACs) have emerged as an alternative

for vitamin K antagonists (VKAs) for thromboembolic prevention

in patients with non-valvular atrial fibrillation (AF). This will have

an impact on many practical considerations in the daily manage-

ment of these patients. Although very promising in many regards

(predictable effect without need for monitoring, fewer food and

drug interactions, shorter plasma half-life, and an improved effi-

cacy/safety ratio), the proper use of NOACs will require new

approaches in many daily aspects. Whereas the 2010 ESC Guide-

lines (and the 2012 Update)1,2 mainly discuss the indications for

anticoagulation in general (e.g. based on the CHA2DS2-VASc

score) and of NOAC in particular, they guide less on how to

* Corresponding author. Tel: + 32-16-34 42 48; fax: + 32-16-34 42 40, Email: Hein.Heidbuchel@uzleuven.be

Advisors: Azhar Ahmad, M.D. (Boehringer Ingelheim Pharma), Susanne Hess, M.D. (Bayer Healthcare Pharmaceuticals), Felix Munzel, Ph.D. (Daiichi Sankyo Europe), Markus

Schwertfeger, M.D. (Daiichi Sankyo Europe), Martin van Eickels, M.D. (Bayer Healthcare Pharmaceuticals), Jean-Philippe Verbist, M.D. (Bristol Myers Squibb/Pfizer).

Document reviewers: Coordinator: Antonio Raviele, Alliance to Fight Atrial Fibrillation (ALFA), Venice-Mestre, Italy.

Leandro Zimerman, M.D. (Hospital deClınicas de Porto Alegre, Brasil), Chern-En Chiang, Ph.D. (Taipei VeteransGeneral Hospital, Taiwan), HansDiener, Ph.D. (University of Essen,

Germany), Giuseppe Di Pasquale, Ph.D. (Ospedale Maggiore, Bologna, Italy), Stephan Hohnloser, Ph.D. (Klinikum der J.-W.-Goethe-Universitat, Frankfurt, Germany), Jean-Yves Le

Heuzey, Ph.D. (Hopital Europeen Georges Pompidou, Paris, France), Jose Lopez-Sendon, Ph.D. (Hospital Universitario La Paz. Madrid, Spain, Jonas Bjerring Olesen, Ph.D. (Copen-

hagen University Hospital Gentofte, Denmark), Frans H Rutten, Ph.D. (Julius Center UMC Utrecht, The Netherlands), Marco Valgimigli, Ph.D. (University Hospital of Ferrara, Italy),

Freek W.A. Verheugt, Ph.D. (Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands), Michael Brainin, Ph.D. (Klinische Medizin Und Praeventionsmedizin, Danube University

Krems, Austria), Kennedy Lees, Ph.D. (University of Glasgow, UK).

Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: journals.permissions@oup.com.

Europace (2013) 15, 625–651

doi:10.1093/europace/eut083

by guest on January 19, 2015D

ownloaded from

Doença coronariana estável

SCA > 1 ano

Stent convencional > 1 mês

Stent farmacológico > 6 mês

Stroke. 2014;45:2160-2236 J Am Coll Cardiol. 2014;64(21):2246-2280

European Heart Journal – cardiovascular imaging 2007 (8), Issue 1, 1

1 2

4 3

Circulation. 2009;119:1616-1624

Circ Heart Fail. 2013;6:988-997

J Stroke Cerebrovasc Dis. 2013 Nov;22(8):1279-87

Stroke. 2014;45:2160-2236

Arq Bras Cardiol 2008; 91(5) : 306-310 Arq Bras Cardiol. 2013; 101(3Supl.3): 1-93

Circulation. 2012;125:2649-2661

J Am Coll Cardiol. 2014;64(21):2246-2280

RECOMENDAÇÕES CLASSE IIa

Síndrome de anticorpo antifosfolípede

Diagnóstico confirmado e AVC/AIT prévio

Trombose venosa cerebral Gestação e amamentação

Heparina

Shimoli V. Shah and Brian F. GageCost-Effectiveness of Dabigatran for Stroke Prophylaxis in Atrial Fibrillation

ISSN: 1524-4539 Copyright © 2011 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online

72514Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX

doi: 10.1161/CIRCULATIONAHA.110.9856552011, 123:2562-2570: originally published online May 23, 2011Circulation

http://circ.ahajournals.org/content/123/22/2562located on the World Wide Web at:

The online version of this article, along with updated information and services, is

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Baixo risco de AVC (CHADS2 = 0)

Alto risco de AVC (CHADS2 > 3)

Médio risco de AVC (CHADS2 = 1-2)

Risco de sangramento 6% ao ano

CoBCMJ 2014;56:391-394

Avaliação de custo efetividade É efetiva e segura Sem bem tolerada previamente não há

necessidade de troca, que inclusive nesse caso não é recomendada

Prezar mais a discussão de tratamento com o paciente