Background
Establishing and maintaining long-term vascular access is a prerequisite for hemodialysis in patients with end-stage renal disease (ESRD) [
1‐
4]. An ideal vascular access should provide sufficient blood flow for hemodialysis to ensure the completion of hemodialysis procedures, as well as long enough use time and as few complications as possible, which is an important condition for sustaining long-term survival [
5]. During the treatment of arteriovenous fistula (AVF), it is possible that anastomotic embolism can often lead to failure of fistula [
6,
7]. Therefore, long-term dialysis patients have to face treatment trouble and mental pain [
8,
9]. ESRD patients are considered at increased risk for vascular thromboembolic events (VTEs) after an AVF surgery [
6]. The use of antiplatelet medications, specifically clopidogrel (CL) and beraprost sodium (BPS), is steadily increasing [
10,
11]. Previous studies show that patients receiving either of these medications are at decreased risk for VTEs after an AVF surgery, but the risk in a large, generalizable Chinese population is unknown [
12,
13]. To our knowledge, a direct comparison between CL and BPS has rarely been reported in the previous literature. Despite poor efficacy in ESRD patients, BPS and CL remain promising options to decrease AVF-related VTEs. Nevertheless, several unanswered questions remain.
The aim of this study was to assess the outcome of CL or BPS using time to first on-study VTEs as the primary endpoint in ESRD cases suffering an AVF surgery in Chinese population to further improve the design of the therapeutic regime.
Discussion
In the current study evaluating time to first on-study VTE among at-risk ESRD patients undergoing an AVF surgery, to our knowledge the largest AVF study to date, the major finding was that BPS demonstrated superiority to CL by decreasing the occurrence of VTEs (primary endpoint) in ESRD patients who underwent an AVF surgery. Notably, CL tended to result in a first on-study VTE within the 1st month after the cessation of drug administration compared with BPS.
At the study start, we hypothesized that excellent primary endpoint would be attributed to CL on account of several previous findings. Unfortunately, in our study, CL was inclined to lead to an increased risk of first on-study VTEs, which seemed to contradict its predictive efficacy of VTEs. The reasons for the finding remain indistinct and can be elaborated different versions in some recent studies in ESRD patients who underwent an AVF surgery [
10,
11]. An explanation for the opposite finding is unhesitatingly unavailable, although CL which is commonly used to prevent ATEs might contribute to the difference [
19]. The occurrence of VTEs remains a life-threatening clinical challenge, although considerable benefits of CL have been showed in previous clinical trials [
20‐
22]. Thus far, several literatures have shown the negative impact of CL variability on VTEs in ESRD patients who underwent an AVF surgery, regardless of the prevention of heart attack and strokes in cardiovascular cases [
23,
24]. Undeniably, our study underscored the potential CL-related risks that CL adopted in ESRD patients, which, compared with BPS, tended to be associated with a poor prognosis.
There is a body of evidence suggesting that poor vascular elasticity and endovascular stenosis underlie a significant proportion of patients of VTEs [
25,
26]. Endometrial damage following an AVF surgery can contribute to the occurrence of VTEs [
25,
27]. In terms of the success rate, there are many substantial studies indicated that BPS has contributed to the improvement of the success rate of AVFs in the ESRD patients compared with CL, although a finding at odds with trends was detected in several previous literatures [
10,
28]. Nevertheless, the superiority of BPS has gained increasing recognition, and low VTEs in BPS is most likely explained by BPS itself [
29]. Although the success rate of VTEs in our study was lower than anticipated, our finding was comparable to the outcome of a previous meta analysis [
27]. Furthermore, consistent with previous studies [
30,
31], high VTEs which were detected in CL-treated cohort were associated with an increased risk of thrombus complication.
Our finding is inconsistent with several reports on the rate of VTEs [
4,
5,
32,
33]. A previous study by Yuo was a retrospective assessment only with a rather small number of cases, and the study failed to have a control group [
30]. Furthermore, in their study the divergent results cannot be explained. A growing but still very limited body of literature has shown that BPS tended to result in VTEs compared with CL [
19,
25]. This difference may be attributed to improved monitoring and management of VTEs. In addition, although VTEs were not detected in other cases with ESRD during the study, treatment in accordance with guidelines is advocated to manage VTE risk, and longer-term follow-up is necessary to ascertain any implications of the drug effect.
This study reflects the advantages of the relatively large sample size, which is inclined to provide statistical power to identify insignificant differences in the primary endpoint. The study excluded those cases with high risk for VTEs. Although such cases would be inclined to suffer a VTE, they also have a high rate of some other complications, which could result in high rates of withdrawal. Although our study has basically achieved the desired results, as a retrospective study that BPS is a more optimistic for ESRD patients in preventing VTEs compared with CL, there are inevitably some limitations. Firstly, between-study comparisons might tend to be confounded by differences in population included. Secondly, surgeon- and patient- related confounders may be inevitable. Nevertheless, improvement in the success rate of VTEs remained noteworthy, which had been proved by the final logistic regression assessment after adjusting some potentially and relatively imbalanced variates.
Conclusions
The study demonstrates, as anticipated, the superiority of BPS over CL in ESRD patients using time to first on-study VTE as the primary study endpoint regardless of the follow-up period. Compared with CL, BPS shows a decreased risk for VTEs, the long-term significance of which remains to be clarified. However, the superior efficacy of BPS in the current study offers preliminary evidence of a benefit–risk that corroborates its application in ESRD cases receiving an AVF surgery.
Acknowledgements
The authors would like to thank Xingfei Zhu for help with retrieval of patients’ notes and radiographs.