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Effect of Clopidogrel on Early Failure of Arteriovenous Fistulas for Hemodialysis - Effect of Clopidogrel on Early Failure of AV Fistulas for Hemodialysis
Description:
The goal of this trial was to evaluate treatment with clopidogrel compared with placebo after the creation of an upper extremity arteriovenous fistula.
Hypothesis:
The use of clopidogrel will be more effective in reducing fistula thrombosis and improving fistula patency.
Study Design
Study Design:
Patients Screened: 1,036
Patients Enrolled: 877
Mean Follow Up: 6 months
Mean Patient Age: 53
Female: 38
Patient Populations:
Patients with chronic renal disease who were anticipated to undergo creation of an arteriovenous fistula for dialysis
Exclusions:
• Active bleeding, peptic ulcer disease, or transfusion in the past 12 months
• Thrombocytopenia (<75,000/µL)
• Coagulopathy
• Hypertension (systolic pressure >200 mm Hg or diastolic pressure >115 mm Hg)
• Liver disease
• Inability to continue antiplatelet medication during the study period
• Pregnancy
• Substance abuse
• Myocardial infarction or cerebrovascular accident in the past 12 months that required uninterrupted use of antiplatelet agents
Primary Endpoints:
Fistula thrombosis at 6 weeks: Thrombosis was defined by inability to detect a bruit by stethoscope exam.
Secondary Endpoints:
Failure to attain suitable dialysis. Suitability for dialysis was defined as the maintenance of dialysis at a flow rate of at least 300 ml/min, for 8 of 12 dialysis sessions during a 30-day period. A less-strict definition of suitability for dialysis was defined as the fistula being used at least 8 times during the ascertainment period.
Drug/Procedures Used:
Patients with chronic renal disease who were anticipated to undergo hemodialysis were randomized to clopidogrel (300 mg loading dose followed by 75 mg daily for 6 weeks, n = 441) versus placebo (n = 436) after the creation of an arteriovenous fistula.
Concomitant Medications:
At baseline, the use of aspirin was 23% versus 23%, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was 56% versus 60%, and statin was 37% versus 39%, respectively, for clopidogrel versus placebo.
Principal Findings:
Study medication was discontinued in 8.4% of the clopidogrel group and 7.6% of the placebo group. Determination of fistula thrombosis occurred in 98.6% of the clopidogrel group and 98.9% of the placebo group.
The primary outcome, fistula thrombosis at 6 weeks, occurred in 12.2% of the clopidogrel group and 19.5% of the placebo group (p = 0.018). There was no interaction of treatment effect according to fistula location (for example, upper arm vs. forearm; p = 0.15) or treatment center location (p = 0.57).
The secondary outcome, failure of the fistula to allow for adequate dialysis, occurred in 61.8% of the clopidogrel group and 59.5% of the placebo group (p = 0.40). Using a less-strict definition for failure, the percentage of patients with fistula failure was still 47.8% versus 52.1% (p = 0.30). There was no difference in any adverse event (15.2% vs. 18.6%; p = 0.20) or bleeding (2.9% vs. 2.8%; p = 0.84), respectively, for clopidogrel versus placebo.
Interpretation:
Among patients with a newly created upper extremity arteriovenous fistula for hemodialysis, the use of clopidogrel for 6 weeks resulted in a significant reduction in fistula thrombosis, as assessed by physical exam. Despite a reduction in fistula thrombosis, the use of clopidogrel did not translate into less fistula failures, as defined by the ability of the fistula to allow for adequate dialysis. Even with applying a less stringent definition for fistula failures, there was still no apparent difference in this outcome with the use of clopidogrel.
The investigators of this trial postulated that fistula thrombosis is one component that affects the ultimate success of a fistula; however, other factors beyond early patency are also important. Alternatively, fistula thrombosis may be the result of fistula failure and not the cause. This study reinforces that fistula maturation is a complex process.
References:
Dember LM, Beck GJ, Allon M, et al., on behalf of the Dialysis Access Consortium Study Group. Effect of Clopidogrel on Early Failure of Arteriovenous Fistulas for Hemodialysis: A Randomized Controlled Trial. JAMA 2008;299:2164-2171.
Presented at the annual meeting of the American Society of Nephrology, 2007
Keywords: Renal Dialysis, Thrombosis, Ticlopidine, Forearm, Renal Insufficiency, Chronic
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