The main findings of our study include: (1) 6-month TLPP rate in dysfunction hemodialysis AVF patients who received DCB was higher than those who were treated with conventional balloon angioplasty; however, this was not statistically significant; (2) there was no evidence supporting that DCB had a significantly lower rate of 6-month TLR; (3) there was no significant difference in terms of access circuit primary patency, access circuit reintervention, or severe adverse events between DCB and conventional balloon angioplasty; (4) substantial inter-heterogeneity among included trials were observed.
This meta-analysis failed to provide evidence supporting that DCB has a statistically significant higher rate of TLPP and lower rates of TLR, as compared to conventional balloon angioplasty within 6 months after the indexed procedure; however, a trend was observed. The study of Trerotola et al. and Lookstein had a significant influence on the pooled estimate of effect. Notably, Trerotola et al. reported an unlike the benefit of DCB for the treatment of dysfunctional AVF compared to conventional balloon angioplasty. In contrast, Lookstein et al. advocated that DCB angioplasty was superior to conventional balloon angioplasty and was non-inferior in terms of adverse events. Substantial heterogeneity was observed among included studies. This heterogeneity may be explained by included trials that used the different brands of DCB devices. In the study of Trerotola et al., the Lutonix balloon with a paclitaxel load of 2 µg /mm2 was used, while in the study of Lookstein, the IN.PACT balloon carrying a paclitaxel dose of 3.5 µg /mm2 was used. Besides drug dose density, excipients are critical components of the DCB (19). In the study of Yin et al., the APERTO DCB with a coating excipient of ammonium salt was used. While coating excipient of Lutonix and IN.PACT was polysorbate-sorbitol and urea, respectively. All these perspectives as mentioned above may lead to a difference in the amount of drug delivered to the target lesion and its efficacy and safety. However, clear evidence in animal experiments of AVF is scarce.
This meta-analysis is different from prior meta-analyses in the following perspectives (20–22): (1) we only included RCTs with generally high quality and relatively larger sample size, which have higher evidence level than observational studies; (2) RCTs included in our study were up to date; (3) we excluded patients who had arteriovenous graft and focused only on AVF. Nevertheless, in the study of Kennedy et al. and Wee et al., retrospective studies and prospective cohorts were included (21, 22). In the study of Liao et al., RCTs with a small sample size and inconclusive results were included, which are likely to be susceptible to publication bias and may, therefore, be less reliable (20).
The limitation of this systematic review and meta-analyses needs to be addressed. First, the overall heterogeneity and risk-of-bias observed in our meta-analysis were attributed to each included original RCT. However, individual-level data are needed to explore the potential cause of heterogeneity fully, however, they were not available for us. Second, publication bias or small-study effect was inspected visually using a funnel plot. Due to the limited number of RCTs, a statistical test for the funnel plot asymmetry was not performed. Third, our pooled results in terms of TLPP should be interpreted with an awareness that in the trial conducted by Yin et al., the definition of TLPP was different from the other three studies, which included a peak systolic velocity ratio lower or equal to 2.0 as determined using doppler ultrasound. Fourth, it is only feasible for us to assess the effectiveness of DCB in terms of the short-term outcomes, i.e. within 6 months after the indexed procedure, long-term outcomes regarding the efficacy and safety wait for longer follow-up results.
In conclusion, we failed to provide evidence supporting that DCB has a statistically significant higher rate of TLPP or lower rates of TLR in the treatment of dysfunctional AVF than conventional balloon angioplasty within 6 months after the indexed procedure. However, DCB was non-inferior to conventional balloon angioplasty in terms of safety. Therefore, further study is needed to clarify whether DCB angioplasty can benefit hemodialysis patients with dysfunction AVF.