EBM98.10.22::

65,,.Permanent Catheter,,.,,(arteriovenous graft).graft.

70,,(ballon angioplasty)(thrombectomy),..

. graftarteriovenous graft,.,???

AVG stenosisDialysis access:The most common cause of arteriovenous failure is thrombosis,which is most commonly secondary to progressive venous outflow stenosis followed by occlusion

5As of EBMAsk : ask an answerable questionAcquire : track down the best evidenceAppraisal : validity, impact, applicabilityApply : to patients problemAudit : effectiveness

Ask Patient:DM with nephropathy and progressed to ESRDHad arteriovenous graft created Intervention:any medicationComparison:placeboOutcome: arteriovenous graft thrombosis

Acquire

AcquirePubmed Main serch:Arteriovenous graftAntithrombosisAdvanced Search:randomised trials or meta-analysis

Acquire

AcquireallEBM reviewMain serch:Arteriovenousantithrombosis

AcquireAntiplatelet Agents Reduce Risks for Death, Stroke, Myocardial Infarction, Deep Venous Thrombosis, and Arterial OcclusionDouble-blind randomized trial of the effect of ticlopidine in arteriovenous fistulas for hemodialysisEffect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trialNo suitable paper for our PICO

Appraisal

AppraisalSelection criteria:RCTs of active drug versus placebo in patients with ESRD undergoing haemodialysis via an A-V fistula or prosthetic interposition AV graftlevel IAOutcome:measure analysed was the long-term fistula or graft patency rate

All randomised trials from electronic searches of MEDLINE (1966 to date), EMBASE (1980 to date) and CINAHL (1982 to date)

Characteristics of included studies

Andrassy 1974Crowther 2002Fiskerstrand 1984Grontoft 1985Grontoft 1998Harter 1979

Michie 1977Schmitz 2002Sreedhara 1994Trimarche 2006All randomised controlled studies

A (low risk of bias) B (moderate risk of bias) C(high risk of bias)

Quality of trials

Andrassy 1974

Aspirin 500mg VS placeboData base 92

Harter 1979

Aspirin 160 mg VS placeboData base 44

Crowther 2002Warfarin VS placeboData base 107

Fiskerstrand 1984Ticlopidine 250mg VS placeboData base 18

Grontoft 1985

Ticlopidine 250 mg VS placeboData base 42

Grontoft 1998

Ticlopidine 250mg VS placeboData base 254

Michie 1977

Sulfinpyrazone 200 mg VS placeboNo show data base

Schmitz 2002

fish oil VS placebo

Data base 24

Sreedhara 1994

1.Dipyridamole 75 mg +aspirin 325mg2.Dipyridamole 75mg3.Aspirin 325 mg4.placebo

Data base 108

Trimarche 2006

Clopidogrel VS placebo

Characteristics of excluded studies

Mata-analysis

Aspirin versus placebo

Cochran Q ( P < 0.1 )(Q/df) > 1

Reduce thrombosis by 58%Aspirin 500Aspirin 160Aspirin 325

Ticlopidine versus placebo

Cochran Q is not statistically significantBut (Q/df) > 1,Reduce thrombosis at one month by 53%All use ticlopidine 250 mg

Dipyridamole versus placebo

Dipyridamole + aspirin versus placebo

Warfarin versus placebo

Fish oil versus placebo

Clopidogrel versus placebo

NEJMN ENGL J MED 360;21 NEJM.ORG May 21, 2009

Method

Include > 18 y/oa new arteriovenous graft placed for the purpose of hemodialysisCurrently undergoing long-term hemodialysisExpected to undergo it within 6 months

Exclude Pregnant or breast-feedingIncreased risk of bleeding or a known bleeding disorderActive esophagitis, gastritis, or peptic ulcer diseasePlatelet count of less than 75,000Advanced liver disease; or required an anticoagulant or antiplatelet agent other than aspirinAllergy to aspirin or dipyridamole

Study Design and ProceduresRandomizationOne capsule contain 200 mg of extended-release dipyridamole plus 25 mg of immediate-release aspirinidentical-looking placebo Followed monthly by ultrasoundFrom July 31,2003~Jaunary 31,2008

RandomizationAccording to the center and access location(forearm or alternative site) with the use of a random permuted-block designPatients were unaware of the treatment assignments

Outcome Primary outcome:Loss of primary unassisted graft patency, defined as the first occurrence of graft thrombosis, an access procedure performed to correct a stenosis of 50% or more of the diameter of the adjacent normal vessel, or other surgical modification of the graft

OutcomeReferred to Angiography:flow

OutcomeSecondary outcomes:Cumulative graft failureDeath from any causeCombined outcome of death from any cause

Statistical Analysis

Cox proportional-hazardsBasis:clinical centerAccess location (forearm or other site)Adjustmentserum albumin leveluse of ACEI of ARB

Statistical Analysis

Aimed to enroll 1056 patients for statistical powerprovide a statistical power of 85% to detect a 25% reduction in the incidence of the primary outcome, with a two-sided type I error rate of 5%.

Result

Study Population

Baseline Characteristics

Female,Black race And DM history

Efficacy

EfficacyPrimary unassisted patency at 1 year:23% VS 28%Median duration of patency:5.8 months VS 4.3 months

Hazard ratio

Secondary outcomeAll had no difference in the two group

Side effect

Side effectno significant difference between the two study groups with regard to any adverse-event category

Bias patient in this study,loss of graft patency in one year,higher than 54% originally predictedMay due to our study population;more woman,black race and DM historyMonthly follow up flow of graft,may increase the loss of graft patency incidence

Apply Aspirin or Ticlopidine or could decrease short term thrombosis;however There is no long term dataFish oil or Clopidogrel or Sulfinpyrazone could decrease decrease short term thrombosis;however data number was small and there is no long term dataWarfarin had no benefit

Suggestion Could use Aspirin(500mg or 160mg) or Ticlopidine(250mg) or dipyridamole (200mg)+aspirin (25mg) if patient has no bleeding tendency

Discussion If there is no obvious side effect,why not try antiplatelet?short term thrombosishemodialysis?