腫瘤患者靜脈血栓栓塞的抗凝治療與管理

腫瘤相關(guān)VTE治療研究進展前言

目前已經(jīng)證實惡性腫瘤與VTE之間關(guān)系密切，惡性腫瘤患者通常處于高凝狀態(tài)，與非惡性腫瘤患者相比，其發(fā)生VTE的風(fēng)險更高。血栓栓塞事件已經(jīng)成為腫瘤患者的第二大死因。腫瘤患者發(fā)生VTE通常初始使用低分子肝素（LMWH）進行抗凝治療，長期抗凝是否可轉(zhuǎn)換為華法林？亦或更換為新型抗凝藥？04020103主要內(nèi)容腫瘤患者VTE初始治療方案腫瘤患者VTE長期治療肝素VS華法林腫瘤患者VTE長期治療DOACs

VS華法林總結(jié)參考文獻1.HighIncidenceofThromboembolicEventsinPatientsTreatedWithCisplatin-BasedChemotherapy:ALargeRetrospectiveAnalysis[J].J

Clin

Oncol.2011,29(25):3466-73.2.Venousthromboembolisminthecanceroutpatientsetting:contemporaryratesandpredictorsintheUnitedStates[J].

Cancer.2013,119(3):648-55.3.Anticoagulationforthelong-termtreatmentofvenousthromboembolisminpatientswithcancer[J].CochraneDatabaseSystRev,2014,8(7).4.Oralrivaroxabanversusstandardtherapyforthetreatmentofsymptomaticvenousthromboembolism:apooledanalysisoftheEINSTEIN-DVTandPErandomizedstudies[J].ThrombJ2013;11:21.5.DirectoralanticoagulantsinpatientswithVTEandcancer:asystematicreviewandmeta-analysis[J].Chest.2015;147(2):475-484.

6.Prosandconsofneworalanticoagulantsinthetreatmentofvenousthromboembolisminpatientswithcancer[J].Inter

Emerg

Med.2015,10(6):651-656.流行病學(xué)1.HighIncidenceofThromboembolicEventsinPatientsTreatedWithCisplatin-BasedChemotherapy:ALargeRetrospectiveAnalysis[J].J

Clin

Oncol.2011,29(25):3466-3473.流行病學(xué)2.Venousthromboembolisminthecanceroutpatientsetting:contemporaryratesandpredictorsintheUnitedStates[J].

Cancer.2013,119(3):648-55.腫瘤患者VTE治療方案選擇2014ASCO211ESMO2016ACCP2016NCCN腫瘤患者VTE治療方案選擇2011EMSO2014ASCO2016CNNC2016ACCPInitial

treatmentLMWH，UFH.Crcl<25–30ml,UFHorLMWHwithanti-Xaactivitymonitoringisrecommended[I,A]LMWHisrecommendedfortheinitial5to10daysoftreatmentofVTE

aswellasforlong-termsecondaryprophylaxisforatleast6months.LMWH,UFH

or

FXa

antagonists

according

to

patient’s

characteristics

and

clinical

situation.LMWH

over

VKA

therapydabigatran,rivar-oxaban,apixaban

or

edoxaban(2C)

at

first

3

months.Long

term

treatment75%-80%

of

the

initial

dose

for

6

months

of

LMWH

is

safe

and

more

effective

than

VKA.(I,A)UseofnoveloralanticoagulantsisnotcurrentlyrecommendedforpatientswithmalignancyandVTE.LMWH

is

preferred.Indefinite

anticoagulation

in

patients

with

active

cancer

or

persistent

risk

factors.extendedanticoagulanttherapy(noscheduledstopdate)over3monthsoftherapy(1B),orhaveahighbleedingrisk,wesuggestextendedanticoagulanttherapy(noscheduledstopdate)over3monthsoftherapy(2B)腫瘤患者發(fā)生VTE時起始治療各指南均推薦LMWH。長期治療藥物選擇方面除ASCO指南說明無法使用LMWH時可選擇VKA，其余均說明LMWH優(yōu)于VKA?；顒有阅[瘤或血栓誘因持續(xù)存在時，療程不確定，長期抗凝優(yōu)于短期抗凝（3個月）。腫瘤患者VTE指南推薦治療方案總結(jié)腫瘤患者VTE長期治療LMWH

VS華法林3.Anticoagulationforthelong-termtreatmentofvenousthromboembolisminpatientswithcancer.CochraneDatabaseSystRev,2014,8(7).10,033

records

identified

through

database

searching55

additional

record

identified

through

other

sources9559

records

after

duplicates

removed9559

records

screened65

full-text

articles

assessed

for

eligibility10

studies

included

in

qualitative

synthesis(11

reports)10

studies

included

in

qualitative

synthesis(meta-analysis)54

full-text

articles

excluded,with

reasons;14=unavailable

data

for

cancer

subgroup;1=case

series;15=review;4=retrospective

study;2=protocol;6=observational

study;4=nonrandomizedtrial;4=no

cancer

patients

included;1=only

one

cancer

patient

included;2=no

relevant

outcome;1=different

durations

of

intervention生存率：使用時間-事件資料，采用pooled

analysis方法，對兩篇已發(fā)表，一篇從作者處獲得的原始資料進行分析。結(jié)果：LMWH與VKA間無統(tǒng)計學(xué)差異

HR0.96；95%

CI

0.81-1.14；I2=0%全因死亡率：采用pooled

analysis方法，分析6個月時的全因死亡率。結(jié)果：LMWH與VKA間無統(tǒng)計學(xué)差異

RR0.97；95%

CI

0.88-1.10；I2=0%LMWH

VS華法林生存率及全因死亡率LMWH

VS華法林生VTE復(fù)發(fā)VTE復(fù)發(fā)：使用時間-事件資料，采用pooled

analysis方法，對兩篇已發(fā)表，一篇從作者處獲得的原始資料進行分析。結(jié)果：LMWH與VKA間有統(tǒng)計學(xué)差異

HR0.47；95%

CI

0.32-0.71；I2=0%LMWH

VS華法出血事件間無統(tǒng)計學(xué)差異文獻小結(jié)雖然LMWH能夠降低VTE的復(fù)發(fā)風(fēng)險，但因其花費較高且需要皮下注射，因此腫瘤患者合并VTE時長期治療選擇LMWH還是華法林應(yīng)綜合評估患者的風(fēng)險和獲益，以及患者的選擇傾向。新型口服抗凝藥與傳統(tǒng)抗凝治療的比較4.Oralrivaroxabanversusstandardtherapyforthetreatmentofsymptomaticvenousthromboembolism:apooledanalysisoftheEINSTEIN-DVTandPErandomizedstudies.ThrombJ2013;11:21.背景：肝素聯(lián)合VKA是治療VTE的標(biāo)準(zhǔn)方法。直接口服抗凝藥已經(jīng)被研究用于VTE的急性和長期治療，其能夠避免胃腸外給藥且不需要實驗室監(jiān)測抗凝療效。方法：通過pooled

analysis比較EINSTEIN-DVT和EINSTEIN-PE研究中利伐沙班（15mg

bid

21d,隨后20mg

qd）和標(biāo)準(zhǔn)療法

（依諾肝素1.0mg/kg

bid序貫華法林或香豆素類抗凝藥）。統(tǒng)計患者3、6、12個月VTE復(fù)發(fā)及出血情況。預(yù)設(shè)的非劣效性邊緣值為1.75。Table

2

Efficacy

a