Rev. Bras. Reumatol. vol.56 número6

r e v b r a s r e u m a t o l . 2016;56(6):469–470

w w w . r e u m a t o l o g i a . c o m . b r

REVISTA

BRASILEIRA

DE

REUMATOLOGIA

Editorial

Direct

oral

anticoagulants

in

antiphospholipid

syndrome

Anticoagulantes

orais

diretos

na

síndrome

antifosfolípide

Antiphospholipid syndrome (APS) is an acquired throm-bophiliacharacterizedbythrombosisand/orfetalloss asso-ciatedornotwiththepresenceofthrombocytopeniainthe presenceofcirculatingantiphospholipidantibodies (anticar-diolipin,lupusanticoagulantand/oranti-beta2-glycoprotein I). Chronic current treatment of this disease includes the useofvitaminK antagonistoralanticoagulants.There isa good response to treatment with oral anticoagulants; this therapyaimsatpreventingnewthromboticevents;however, re-thrombosisratesof16%coveringatimespanof10years were described.1 _{In this review, the authors found a high}

rateofre-thrombosisintriple-positive(anticardiolipin,lupus anticoagulantandanti-beta2-glycoproteinI)patients(44%in 10 years). However, these medications are associated with variousdruginteractions and aregreatly influencedbythe dietaryvitaminK intake.2 _{Itisimportantthat adjustments}

andmaintenancecontrolsarecarriedout,basedon prothrom-bintime(throughcontroloftheinternationalnormalization ratio –INR) regularly performedthroughout the lifeofthe patient,whichreduceshis/hertherapeuticadherence. More-over,insomecases,thelupusanticoagulantcanchangethe prothrombintimeandcompromisethepatient’smonitoring. Another disadvantageisthe decrease inC and Sproteins, whicharenaturalanticoagulants,withapossibleincreased riskofthrombosisintheacutephaseofanticoagulation.3

Hence,anewclassoforalanticoagulantdrugs(directoral anticoagulants)emerged,withtheadvantageofnotrequiring alaboratorycontrol,withtheaddedbenefitofbeingverylittle influencedfromfoodandothermedications.Examplesofsuch drugsare dabigatran, which is adirectthrombin inhibitor, andrivaroxaban,apixaban,and edoxaban,whicharefactor Xainhibitors.SuchdrugsareapprovedbytheFDAforusein venousthromboembolicevents andincasesofatrial fibril-lationinthe generalpopulation. Therearefewreportsand studiesontheuseofthesemedicationsinpatientswithAPS.

Table1summarizesthestudieswithdabigatranor

rivaroxa-baninAPS.

Intheliterature,about85casesofpatientswithAPSwho have taken the new oralanticoagulants were found. Most ofthesepapersare casereportsor seriesofcases,besides two retrospective studies and one prospective study. The medianfollow-uptimerangedfrom10to19monthsandthe most widely used medication was rivaroxaban. The recur-rencerangedfrom0to17%,includingseveralarterialevents, whenonlystudiesthatreportedthenumberofrecurrences inrelationtothenumber ofpatientsatrisk whowere fol-lowedforaperiodoftimewereevaluated.Thevastmajority ofpatientsincludedinallstudieshadsufferedprevious arte-rialeventsormultiplerecurrencesinthepresenceofvitamin K antagonists, or discontinued the use of the anticoagu-lant,or,ultimately,weretriple-positiveforantiphospholipid antibodies.4–9

Twoprospectiverandomizedstudies,oneofItalianorigin (TRAPS)andanotherEnglish(RAPS),3_{currentlyinafollow-up}

phaseofpatientswithAPS,withagrouptreatedwithwarfarin versusrivaroxaban,werepublished.Thesestudieswillprovide theanswerstothisquestion.

470

Table1–Summaryofcaseseries,prospectiveandretrospectivestudiesontheuseofneworalanticoagulantsinpatients withantiphospholipidsyndrome.

Author,year N Primary APS

Studytype Follow-up Previous arterialevent

Triple positive

Anticoagulant Recurrence

Noeletal.,20155 _{26 12/26 Retrospectivecohort 19m 12/26 7/26 Rivaroxaban}

(n=15), dabigatran (n=11)

1(4%)

Sciasciaetal.,20156 _{35 Prospectivecohort 10m 0 ND Rivaroxaban 0}

Sonetal.,20157 _{12 8/12 Caseseries 12m 2/12 5/12 Rivaroxaban 2(17%)[2SLE,}

1previous arterialevent, 1patient discontinued Rivaroxaban6d] Schaeferetal.,20148 _{3 2/3 Retrospectivecohort NA 2/3 1/3 Rivaroxaban}

(n=2),dabigatran (n=1)

3(100%)

Winetal.,20149 _{3 3/3 Caseseries NA 2/3 ND Rivaroxaban 2venous,}

1arterialevent

Signorellietal.,20154 _{8 8/8 Caseseries NA 2/8 3/8 Rivaroxaban 6arterial,}

2venousevents

NA,notapplicable;ND,notdetermined;SLE,systemiclupuserythematosus.

Funding

CarvalhoJF received grants from Federico Foundation and CNPq(300665/2009-1);LevyRAreceivedagrantfromFederico Foundation;LevyRAand AndradeDC aremembers ofAPS Action.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

r

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f

e

r

e

n

c

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s

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JozélioFreiredeCarvalhoa,∗,

DanieleCastroOliveiradeAndradeb_,RogerA.Levyc

a_{UniversidadeFederaldaBahia,InstitutodeCiênciasdaSaúde,}

Salvador,BA,Brasil b_{UniversidadedeSãoPaulo,FaculdadedeMedicina,}

DivisãodeReumatologia,SãoPaulo,SP,Brazil c_{UniversidadedoEstadodoRiodeJaneiro,Divisãode}

Reumatologia,RiodeJaneiro,RJ,Brazil

∗_{Correspondingauthor.}

E-mail:jotafc@gmail.com(J.F.Carvalho). 2255-5021/©2016ElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBY-NC-NDlicense(http://

creativecommons.org/licenses/by-nc-nd/4.0/).