作者：Laurie Barclay, MD 齣處：WebMD醫學新聞 　　May 20, 2009 — 根據一項發錶在5月21日新英格蘭醫學期刊的隨機分派、雙盲、安慰劑控製研究結果 以dipyrid Dipyridamole加上Aspirin可能改善透析患者人工血管暢通率 - 趣味新聞網

發表日期 2009-06-07T08:01:40+08:00

     本帖最後由 lsc0019 於 2009-6-7 22:44 編輯

作者：Laurie Barclay, MD
齣處：WebMD醫學新聞

May 20, 2009 — 根據一項發錶在5月21日新英格蘭醫學期刊的隨機分派、雙盲、安慰劑控製研究結果，以dipyridamole加上aspirin可以改善透析患者人工血管暢通率。

愛荷華市退伍軍人醫學中心與愛荷華大學的Bradley S. Dixon醫師，與其來自透析管路聯閤研究團隊的同事錶示，動靜脈人工血管狹窄造成的栓塞是接受透析病患發生併發癥最主要的原因。與醫療措施相關的介入可能恢復人工血管的暢通，但這是昂貴的。雖然目前並沒有有效的藥物治療，但dipyridamole因其抑製血管增殖活性的作用而具潛力。

這項研究評估緩釋劑型dipyridamole（200 mg）與aspirin（25 mg）每天兩次，在放置新的動靜脈人工血管後開始投予，直到達到試驗終點。主要的試驗終點是失去主要未支撐的血管暢通性，以未發生栓塞或是需要介入的暢通定義，而次級試驗終點是纍積血管暢通失敗率以及死亡率。以Cox比例風險迴歸模式，校正特定預先設定的共變項，分析主要與次要預後。

研究樣本總共有649位病患，這些病患從美國13個中心收納，且被隨機分派接受dipyridamole與aspirin（共321位）或是安慰劑（共328位），後續追蹤平均4.5年，且額外再觀察6個月。在一年時，安慰劑組的主要未支撐血管暢通度為23%（95%信賴區間為18%-28%），dipyridamole-aspirin組則是28%（95%信賴區間為23%至34%），絕對差異為5%。

相較於安慰劑組，dipyridamole加上aspirin狹窄的比例較低，且主要未支撐暢通度時間顯著較長（危險比值[HR]為0.82；95%信賴區間為0.68-0.98；P=0.03）。實驗組纍積人工血管失敗率、死亡率、血管失敗率或是死亡或是嚴重不良反應(包括齣血)的綜閤終點都沒有顯著差異。

研究作者們錶示，以dipyridamole加上aspirin有降低血管狹窄顯著但適度的作用，且可以改善新的血管主要未經支撐暢通度。與緩釋型dipyridamole加上aspirin過去已知抗血管增殖作用相同，該研究結果顯示，針對血管新生內皮增生的策略是個值得之後研究的重要領域。

這項研究的限製包括未能達到收納目標、限製次組分析的可行性。除此之外，無法確立以dipyridamole加上aspirin持續治療對於纍積人工血管暢通可能的好處，因為這是一旦達試驗終點後即停止的研究。

在隨後的主編評論中，來自加拿大安大略多倫多大學的Charmaine E. Lok醫師錶示，這項研究可能也協助釐清是否應該要常規監測人工血管的管內血流。

Lok醫師寫到，Dixon等人的研究在報告提供改善的介入是獨特的，盡管對人工血管預後隻有適度好處，但並不會顯著增加不良事件風險。雖然缺乏正式、經濟效益的分析，且進行中的療法對人工血管持續時間的纍積效應仍然未知，但dipyridamole-aspirin治療顯然是低風險、可廣泛應用的介入，對那些動靜脈人工血管是維持生命必須的透析病患，可能延長管路暢通性。

國傢糖尿病與消化及腎髒疾病機構、國傢衛生研究院、百靈佳藥廠贊助這項研究。百靈佳藥廠也提供持續釋放型dipyridamole-aspirin與相對應的安慰劑。部分研究作者錶示與Proteon治療公司、Pervasis治療公司、Renal Advantage公司、百靈佳藥廠、亞培實驗室、Genzyme、Angiotech、Bellus Amgen研究三角機構、禮來藥廠、輝瑞藥廠與DeCode基因公司有不同程度的資金往來。

Lok醫師錶示接受Shire、DeCode基因公司的顧問費。

TDipyridamole Plus Aspirin May Improve Hemodialysis Graft Patency

By Laurie Barclay, MD
Medscape Medical News

May 20, 2009 — Treatment with dipyridamole plus aspirin improves hemodialysis graft patency, according to the results of a randomized, double-blind, placebo-controlled trial reported in the May 21 issue of the New England Journal of Medicine.

"Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis," write Bradley S. Dixon, MD, from the University of Iowa and the Veterans Affairs Medical Center in Iowa City and colleagues from the Dialysis Access Consortium Study Group. "Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity."

This trial evaluated the combination of extended-release dipyridamole (200 mg) and aspirin (25?mg) administered twice daily after the placement of a new arteriovenous graft until the main endpoint of the study was reached. That primary outcome was loss of primary unassisted patency, defined as patency without thrombosis or requirement for intervention, and secondary outcomes were cumulative graft failure and mortality. A Cox proportional-hazards regression with adjustment for prespecified covariates was used to analyze primary and secondary outcomes.

The study sample consisted of 649 patients who were recruited from 13 centers in the United States and randomly assigned to receive dipyridamole plus aspirin (n = 321) or placebo (n = 328) during a period of 4.5 years and who were observed for 6 additional months. At 1 year, the incidence of primary unassisted patency was 23% in the placebo group (95% confidence interval [CI], 18% - 28%) vs 28% in the dipyridamole-aspirin group (95% CI, 23% - 34%), yielding an absolute difference of 5 percentage points.

Compared with the placebo group, the dipyridamole plus aspirin group had less stenosis and a significantly longer duration of primary unassisted patency (hazard ratio [HR], 0.82; 95% CI, 0.68 - 0.98; P = .03). The study groups were not significantly different in the incidences of cumulative graft failure, mortality, the composite of graft failure or death, or serious adverse events including bleeding.

"Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts," the study authors write. "As is consistent with the known antiproliferative effects of extended-release dipyridamole plus aspirin, the results suggest that strategies targeting neointimal hyperplasia may be an important area for future research."

Limitations of this study include failure to meet the enrollment goal, limiting the applicability of the subgroup analyses. Furthermore, the possible benefit of continuing treatment with dipyridamole plus aspirin on cumulative graft patency could not be determined because the study drug was stopped once the primary outcome was reached.

In an accompanying editorial, Charmaine E. Lok, MD, from the University of Toronto in Ontario, Canada, notes that this study may also help clarify the issue of whether intra-access flow in grafts should be monitored routinely.

"The study by Dixon et al. is unique in reporting on an intervention that provides an improvement, albeit modest, in graft outcomes without an excessive risk of adverse events," Dr. Lok writes. "Though a formal cost-effectiveness analysis is lacking and the cumulative effect of ongoing therapy on graft survival is unknown, dipyridamole-aspirin therapy appears to be a low-risk, broadly applicable intervention that may prolong access patency among patients undergoing hemodialysis whose arteriovenous graft is a lifeline."

The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and Boehringer Ingelheim Pharmaceuticals supported this study. Boehringer Ingelheim Pharmaceuticals also provided the extended-release dipyridamole plus aspirin and matched placebo. Some of the study authors have disclosed various financial relationships with Proteon Therapeutics, Pervasis Therapeutics, Renal Advantage, Boehringer Ingelheim Pharmaceuticals, Abbott Laboratories, Genzyme, Angiotech, Bellus Health (formerly Neurochem), Novartis, GlaxoSmithKline, Merck, Ortho Biotech, GE Healthcare, Amgen-Research Triangle Institute, Eli Lilly, Pfizer, and DeCode Genetics.

Dr. Lok has received consulting fees from Shire, Genzyme, and Amgen.

N Engl J Med. 2009;360:2191-2201, 2240-2242.

分享鏈接