Drug-coated balloons for dysfunctional hemodialysis venous access: A patient-level meta-analysis of randomized controlled trials

ABSTRACT Purpose To perform an individual patient data-level meta-analysis of randomized controlled trials comparing drug-coated balloon angioplasty (DCB) against conventional percutaneous transluminal angioplasty (PTA) in the treatment of dysfunctional hemodialysis venous access. Methods A search was conducted from inception till 13 th November 2020. Kaplan-Meier curves comparing DCB to PTA by target lesion primary patency (TLPP) and access circuit primary patency (ACPP) were graphically reconstructed to retrieve patient-level data. One-stage meta-analyses with Cox-models with random-effects gramma-frailties were conducted to determine hazard ratios (HRs). Dynamic restricted mean survival times (RMST) were conducted in view of violation of the proportional hazards assumption. Conventional two-stage meta-analyses and network meta-analyses under random-effects Frequentist models were conducted to determine overall and comparative outcomes of paclitaxel concentrations utilised. Where outliers were consistently detected through outlier and influence analyses, sensitivity analyses excluding those studies were conducted. Results Among 10 RCTs (1,207 patients), HRs across all models favoured DCB (one-stage shared-frailty HR=0.62, 95%-CI: 0.53–0.73, P<0.001; two-stage random-effects HR=0.60, 95%-CI: 0.42–0.86, P=0.018, I 2 =65%) for TLPP. Evidence of time-varying effects (P=0.005) was found. TLPP RMST was +3.47 months (25.0%) longer in DCB-treated patients compared to PTA (P=0.001) at 3-years. TLPP at 6-months, 1-year and 2-years was 75.3% vs 58.0%, 51.1% vs 37.1% and 31.3% vs 26.0% for DCB and PTA respectively. P-Scores within the Frequentist network meta-analysis suggest that higher concentrations of paclitaxel were associated with better TLPP and ACPP. Among 6 RCTs (854 patients), the one-stage model favoured DCB (shared-frailty HR=0.72, 95%-CI: 0.60–0.87, P<0.001) for ACPP. Conversely, the two-stage random-effects model demonstrated no significant difference (HR=0.76, 95%-CI: 0.35–1.67, P=0.414, I 2 =81%). Sensitivity analysis excluding outliers significantly favoured DCB (HR=0.61, 95%-CI: 0.41–0.91, P=0.027, I 2 =62%). Conclusion Overall evidence suggests that DCB is favoured over PTA in TLPP and ACPP. The increased efficacy of higher concentrations of paclitaxel may warrant further investigation.