透析管路患者使用塗藥氣球進行血管成形術的效益

Abstract

背景介紹 再狹窄仍然是血液透析管路的重要問題。血管成形術使用藥物塗層氣球可減少周邊和冠狀動脈疾病的再狹窄。紫杉醇塗層的氣球導管可以減少透析管路的內膜增生。但目前尚無研究專門評估其對洗腎管路的作用。我們研究目的在於血管成形術使用藥物塗層氣球和常規氣球對於洗腎管路的作用。

方法與程序 第一部分是由研究者發起的單中心、單盲、前瞻性隨機對照試驗，我們隨機分派了44例患有靜脈吻合口狹窄的患者，於2015年7月至2019年8月接受藥物塗層氣球（22例）或常規氣球（22例）進行血管成形術。透析管路的功能是根據各血液透析中心的觀察追蹤；病患經血管成形術後每2個月進行一次輔助性血管攝影追蹤，持續1年。主要結果是6個月時目標病變的初級通暢率。次要結果包括血管成形術後的血管攝影和臨床成功率，6個月和1年時的透析管路初級通暢率和1年時目標病變的初級通暢率。 第二部分是在MEDLINE，EMBASE和CENTRAL數據庫中進行全面搜索，以便確定評估使用藥物塗層氣球進行血管成形術治療透析通路的隨機對照試驗。主要結果為6個月的目標病變初級通暢率，次要結果為12個月的目標病變初級通暢率和與手術相關的併發症。使用相對風險比與次族群的統計分析。 結果 在臨床試驗部分，6個月時，藥物塗層氣球組的目標病變初級通暢率顯著高於常規氣球組（41％比9％；危險比為0.393；95％信賴區間為0.194-0.795；P = .006），以及透析管路的初級通暢率（36％比9％；危險比為0.436；95％信賴區間為0.218-0.870；P = .013）。在1年時，藥物塗層氣球組的目標病變初級通暢率仍然高於常規氣球組（23％比9％；危險比為0.477；95％信賴區間為0.243-0.933；P = .019），但透析管路的初級通暢率沒有顯著不同（14％比9％；危險比為0.552；95％信賴區間為0.288-1.059；P = .056）。沒有觀察到血管攝影和臨床成功率的差異；沒有發現重大併發症。 在系統性的回顧和統合分析部分，收錄11個隨機對照試驗，包括487例接受藥物塗層氣球血管成形術治療的患者和489例接受常規氣球血管成形術治療的患者。在6個月時，目標病變的初級通暢率無顯著差異（相對風險比0.75；95％信賴區間為0.56-1.01；p = .06），並且在12個月時（相對風險比0.89；95％信賴區間為0.79-1.00； p = .06）。即使在自體透析管路或不包括中心靜脈狹窄的研究次族群分析中，藥物塗層氣球組仍然沒有獲益。兩組之間手術相關併發症的風險沒有差異（相對風險比1.00；95％信賴區間為0.98-1.02；p = .95）。 討論與結論 使用藥物塗層氣球於血管成形術於人工透析管路靜脈吻合口狹窄處，6個月時的初級通暢率有所改善。短期的改善無法持續到1年，最終還是需要重新進行血管成形術。（NCT03388892） 系統性的回顧和統合分析發現，使用藥物塗層氣球進行血管成形術，治療透析通路功能障礙並未顯示出明顯的通暢率。另外注意到各個研究中通暢結果有廣泛的差異。因此有必要針對特定類型的透析通路或病變進行進一步研究，以顯示藥物塗層氣球在透析通路中的價值。（PROSPERO編號CRD42019119938）

Introduction Restenosis remains a significant problem in endovascular therapy for hemodialysis vascular access. Drug-coated balloon (DCB) angioplasty decreases restenosis in peripheral and coronary artery diseases. Paclitaxel-coated balloons are used to reduce neointimal hyperplasia in native arteriovenous (AV) fistulas. However, no study evaluated their effect on dialysis access. We aimed to compare the efficacy of angioplasty with drug-coated balloons (DCBs) and angioplasty with conventional balloons (CBs) for dialysis access. Materials and Methods The first part is an investigator-initiated, single-center, single-blinded, prospective randomized controlled trial, we randomly assigned 44 patients who had venous anastomotic stenosis to undergo angioplasty with DCBs (n = 22) or CBs (n = 22) from July 2015 to August 2018. Access function was observed per the hemodialysis center’s protocols; ancillary angiographic follow-up was performed every 2 months for 1 year after the interventions. The primary end point was target lesion primary patency at 6 months. Secondary outcomes included anatomic and clinical success after angioplasty, circuit primary patency at 6 months and 1 year, and target lesion primary patency at 1 year. The second part is a systematic review and meta-analysis. A comprehensive search in the MEDLINE, EMBASE, and CENTRAL databases was conducted in order to identify eligible randomized controlled trials evaluating DCB angioplasty for hemodialysis vascular access dysfunction. The primary endpoint was the 6-month target lesion primary patency and the secondary endpoints were 12-month target lesion primary patency and procedure-related complications. Risk ratios (RR) were pooled and relevant subgroups were analyzed separately. Results In the first part of randomized controlled trial, at 6 months, target lesion primary patency in the DCB group was significantly greater than CB group (41% vs 9%; hazard ratio [HR], 0.393; 95% confidence interval [CI], 0.194-0.795; P = .006), as was the primary patency of the entire access circuit (36% vs 9%; HR, 0.436; 95% CI, 0.218-0.870; P = .013). At 1 year, the target lesion primary patency in the DCB group remained greater than that in the CB group (23% vs 9%; HR, 0.477; 95% CI, 0.243-0.933; P = .019) but not the primary patency of the access circuit (14% vs 9%; HR, 0.552; 95% CI, 0.288-1.059; P = .056). No difference in anatomic or clinical success and major complications were observed. In the second part of systematic review and meta-analysis, eleven randomized controlled trials comprised of 487 patients treated with DCB angioplasty and 489 patients treated with CB angioplasty were included. There were no significant differences in the target lesion primary patency at 6 months [RR, 0.75; 95% confidence interval (CI), 0.56, 1.01; p = 0.06] and at 12 months (RR 0.89; 95% CI, 0.79, 1.00; p = 0.06). The absence of benefit for the DCB group remained, even in the arteriovenous fistula subgroup or the subgroup of studies excluding central vein stenosis. The risk of procedure-related complication did not differ between the two groups (RR 1.00; 95% CI 0.98, 1.02; p = 0.95). Discussion and conclusions Angioplasty with DCBs showed a modest improvement in primary patency of venous anastomotic stenosis and all dialysis AV grafts at 6 months. The short-term benefit was not durable to 1 year, and reinterventions were eventually needed. (NCT03388892) DCB angioplasty did not demonstrate significant patency benefit for the treatment of hemodialysis vascular access dysfunction. Wide variations in patency outcomes across studies were noted. Further studies focusing on specific types of access or lesions are warranted to clarify the value of DCB for hemodialysis vascular access. (PROSPERO Number CRD42019119938)