Pathogenesis and Prevention of Vascular Access Failure DOI: http://dx.doi.org/10.5772/intechopen.83525

Vascugel

94

Trial Conte et al.

Phase I/II

57

 CAD (100%), DM

(68%),

Dyslipidemia

(53%)

AVF (47%) AVG

Vascugel placement at

Placebo

 6

 Safety at 30 days

Primary patency AVG 38% vs 23%, NS

AVF 60% vs 62%, NS

Vascular Access Surgery - Tips and Tricks

Assisted primary

patency

AVG 72% vs 58%, NS AVF 96% vs 88%, NS

(incidence of infection,

intervention

 and

thrombosis)

10.9% vs 21.1%, NS

newly formed access

(51%)

clinical study

[121]

Antiproliferative

Trial Paulson et al.

Phase II

12

 HTN (83%), DM

AVG

 Surgical placement of

NR

 24

 Safety (freedom from

Pharmacokinetics

sirolimus release Whole blood sirolimus

levels reached a mean

 of

> device related adverse

events)

Endpoint met, nil adverse

events

peak of 4.8 ng/mL at 6 h

and were less than 1 ng/

mL at 1 week

Success of COLL-R

implantation

100% success Primary unassisted

graft patency 75% at 12 months and

38% at 24 months

PTFE grafts and COLL-

R

(8%)

[122]

clinical study

Study

 Number of participants

 agents

—COLL-R

(drug-eluted

combination

 product of collagen membrane and sirolimus)

Co-morbidities

 Access type

Intervention

 Control

 Treatment

Primary outcome

 Secondary outcomes

follow-up

(months)

Study

 Number of

Co-morbidities

 Access type

Intervention

 Control

 Treatment

Primary outcome

Secondary outcomes

(Vascugel vs placebo)

follow-up

(Vascugel vs placebo)

(months)

placebo (32% vs 72%, odds ratio [OR] 0.18, 95% confidence interval [CI] 0.05–0.66, p < 0.01) after a mean follow-up of 5 months [67]. In contrary, a randomized, double-blind, placebo-controlled parallel group study [69] assessing the effect of dipyridamole and/or aspirin on AVG thrombosis showed a non-significant increase in thrombosis in 10 of 20 patients (50%) treated with 325 mg of aspirin daily compared to 6 of 19 (32%) patients on placebo (relative risk [RR] 1.99, 95% CI 0.88–4.48, p = 0.18) over a 18-month follow-up period. Inconsistent outcomes have also been described for aspirin used for prevention of AVF failure. In a study of 92 participants [68] randomized to 1000 mg of aspirin on alternate days over a 28 day period or placebo, the frequency of AVF thrombosis was reduced more than 4-fold by aspirin compared to placebo (2 of 45 [4.4%] vs 11 of 47 [23.4%], p < 0.05). However, the most recent and largest RCT showed no significant reduction in AVF failure at 12 months in 488 patients randomized to receive 100 mg of aspirin or placebo for 3 months following AVF creation. AVF failure was defined as a composite of AVF thrombosis, AVF abandonment and cannulation failure [5]. Neither the composite binary outcome (45% participants treated with aspirin vs 43% treated with placebo, RR 1.05, 95% CI 0.84–1.31, p = 0.68) nor the individual outcome components were reduced by low-dose aspirin: AVF thrombosis (20% vs 18%, RR 1.09, 95% CI 0.72–1.64, p = 0.70), AVF abandonment (24% vs 18%, RR 1.31, 95% CI 0.89–1.95, p = 0.17) and cannulation failure (40% vs 39%, RR 0.99, 95% CI 0.76–1.27, p = 0.92) [5]. Differences in treatment dose, duration, sample size and outcome definition makes comparison of treatment efficacy across trials difficult. Considering the cumulative evidence to date, there remains considerable uncertainty as to whether aspirin reduces arteriovenous access failure.

diphosphate (ADP) receptors on the platelet surface, preventing activation of the GPIIb/IIa receptor complex and reducing platelet aggregation [13]. The effects of clopidogrel (300 mg load followed by 75 mg daily) on access failure were evaluated in an RCT involving 877 patients undergoing AVF formation (Table 1). The rate of early fistula thrombosis (within 6 weeks) was lower with treatment (53 of 436 patients, 12.2%) compared to placebo (84 of the 430, 19.5%; RR 0.63, 95% CI 0.46– 0.97, p = 0.18) [15], however, this benefit did not translate into an increase in the proportion of AVFs that became suitable for hemodialysis (61.8% vs 59.5%; RR 1.05, 95% CI 0.94–1.17, p = 0.4) [15]. A smaller RCT of 93 patients found that, compared with placebo, clopidogrel resulted in a lower risk of early fistula thrombosis (5.2% vs 21.6%; HR 0.72, 95% CI 0.41–1.01, p = 0.03) and a higher rate of first successful dialysis using the newly created AVF (92.3% vs 70.5%) [73]. In contrast, no benefit was identified from clopidogrel 75 mg and aspirin 325 mg vs placebo on graft thrombosis in an RCT involving 200 participants undergoing hemodialysis with newly formed AVGs (HR 0.81, 95% CI 0.47–1.40, p = 0.45) [74]. Considering the evidence to date, there remains uncertainty as to whether clopidogrel results in

Pathogenesis and Prevention of Vascular Access Failure DOI: http://dx.doi.org/10.5772/intechopen.83525

a clinically meaningful benefit beyond prevention of early thrombosis.

systematic review and meta-analysis of these trials [78] favored the use of ticlopidine in access thrombosis as a beneficial treatment (OR 0.45, 95% CI 0.25–

uncertain (3 trials, 956 participants, RR 0.94, 95% CI 0.80–1.10) [79]. Based on the available evidence, there may be a short-term benefit of antiplatelet agents in reducing arteriovenous access thrombosis [15, 78–80], though clinically meaningful benefits, including improved long-term patency or access usability for dialysis, have not been found [15, 79]. Therapeutic approaches

4.1.2 Omega-3 fatty acid supplementation (fish oil)

A meta-analysis of 21 RCTs using any type of antiplatelet drug to prevent arteriovenous access failure demonstrated a 51% reduction in patency loss of AVFs with antiplatelet therapy compared to placebo (6 trials, 1222 participants, RR 0.49, 95% CI 0.30–0.81), while clinical benefits in preventing AVG thrombosis remained

targeting vascular remodeling and neointimal hyperplasia may be more beneficial in

Omega-3 fatty acids (the active component of fish oil) are thought to reduce arteriovenous access thrombosis and improve maturation [81] through their antiproliferative [82], antiaggregatory [83], anti-inflammatory [84], antioxidant

Two RCTs have assessed the effect of fish oil on AVG patency (Table 1) [88, 89]. The largest study involved 196 patients with newly created AVGs treated with 4 g of fish oil or placebo for 12 months [89]. There was no statistically

Three RCTs investigated the effects of ticlopidine on AVF thrombosis at 4 weeks (Table 1). Two small RCTs [75, 76] demonstrated that AVF thrombosis occurred in fewer patients receiving ticlopidine as compared with placebo. Grontoft et al. [75] studied 36 participants and showed that AVF thrombosis at 4 weeks was reduced in participants treated with 250 mg ticlopidine twice daily (11%) compared to placebo (47%, p < 0.05). In a pilot study of 18 participants [76], 250 mg ticlopidine given twice daily over 1 month resulted in half the thrombosis rates compared to placebo (25% vs 50% respectively). A multicenter RCT involving 250 participants [77] showed that ticlopidine did not significantly reduce AVF thrombosis compared to placebo at 4 weeks (12% vs 19%, OR 0.6, 95% CI 0.30–1.18, p = 0.1). A subsequent

4.1.1.4 Ticlopidine

0.82, p = 0.009).

the longer term [13].

97

and vasodilatory effects [85–87].
