O-020 - ROBUSTNESS OF MID-TERM AND LONG-TERM SAFETY AND EFFICACY AFTER PACLITAXEL-BASED ENDOVASCULAR THERAPY FOR TREATMENT OF FEMORO-POPLITEAL ARTERY OCCLUSIVE DISEASE. AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

TOPIC:
Peripheral Occlusive Arterial Disease
AUTHORS:
D'Oria M. (University Hospital of Trieste ~ Trieste ~ Italy) , Behrendt C. (University Medical Centre Hamburg-Eppendorf ~ Hamburg ~ Germany) , Veraldi G.F. (University Hospital and Trust of Verona ~ Verona ~ Italy) , Mastrorilli D. (University Hospital and Trust of Verona ~ Verona ~ Italy) , Mezzetto L. (University Hospital and Trust of Verona ~ Verona ~ Italy) , Lepidi S. (University Hospital of Trieste ~ Trieste ~ Italy)
Introduction:
The aims of this study were: i) to assess fragility indices (FI) of individual randomized controlled trials (RCT) that compared paclitaxel-based drug-coated balloons (DCB) or drug-eluting stents (DES) versus standard endovascular devices, and ii) to meta-analyze mid-term and long-term safety and efficacy outcomes from available RCT while also estimating the FI of pooled results.
Methods:
This systematic review has been registered in the PROSPERO public database (CRD42022304326 http://www.crd.york.ac.uk/PROSPERO). Electronic search of PubMed (Medline), EMBASE (Excerpta Medical Database), Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials) was performed for eligible RCT. Rates of primary patency (PP) and target lesion revascularization (TLR) were assessed as efficacy outcomes, while lower limb amputation (LLA) and all-cause mortality were estimated as safety outcomes. All outcomes were pooled with a random effects model to account for any clinical and study design heterogeneity. The analyses were performed by dividing the RCTs according to their maximal follow-up length (mid-term was defined as results up to 2-3 years while long-term was defined as results up to 4-5 years). For each individual outcome, the fragility index (FI) and reverse fragility index (RFI) were calculated according to whether the outcome results were statistically significant or not, respectively. The fragility quotient (FQ) and reverse fragility quotient (RFQ), which are the FI or RFI divided by the sample size, were also calculated.
Results:
A total of 2337 patients were included in quantitative synthesis and meta-analysis. There were 2 RCTs with a DES and 14 RCTs testing different DCBs. Seven RCTs had a maximum follow-up of 2 years while three RCTs reported data with a maximum follow-up of 3 years, and were collectively analysed as mid-term. Three RCTs reached a maximum follow-up of 5 years, and were collectively analysed as long-term. For efficacy outcomes, there was evidence that paclitaxel-based endovascular therapy increased the PP rate and reduced the TLR rate at mid-term, with a calculated pooled RR of 1.66 (95%CI, 1.55-1.86; P<.001), with a corresponding NNT of 3 patients (95%CI, 2.9-3.8). and 0.44 (95%CI, 0.35-0.54; P =.027), respectively. Similarly, there was evidence that paclitaxel-based endovascular therapy increased the PP rate and decreased the TLR rate at long-term, with a calculated pooled RR of 1.73 (95%CI, 1.12-2.61; P=.004) and 0.53 (95%CI, 0.45-0.62; P =.82), respectively. For safety outcomes. there was evidence that paclitaxel-based endovascular therapy increased all-cause mortality at mid-term, with a calculated pooled RR of 2.05 (95%CI, 1.21-3.24). However, there was no evidence that paclitaxel-based endovascular therapy either increased or decreased LLA at mid-term neither all-cause mortality or LLA at long-term, with a calculated pooled RR of 0.66 (95%CI, 0.1-2.7; P =.68), 1.02 (95%CI, 0.31-3.42), and 1.02 (95% CI, 0.30-5.21; P =.22), respectively. The pooled estimates of PP at mid-term were robust (FI=28 and FQ=1.9%) as were pooled rates of TLR (FI=18 and FQ=0.9%). However, when safety outcomes were analysed, the robustness of the meta-analysis dropped. In fact, the relationship between the use of paclitaxel-coated devices and all-cause mortality at mid-term showed very low robustness (FI=4 and FQ=0.2%). At five years, only the benefit of paclitaxel-based devices to reduce TLR remained robust, with a FI of 32 and a FQ of 3.1%.
Conclusion:
In conclusion, the efficacy endpoints of PP and TLR for paclitaxel-based endovascular therapy in the femoro-popliteal artery were consistent and robust across RCT. In contrast, the safety endpoint of all-cause mortality was overall significant only at mid-term but highly fragile, with high rates of lost-to follow-up in the original studies.