使用隨機對照性試驗之網絡統合分析比較Alteplase以外的急性缺血性中風治療方式之療效及安全性研究

Abstract

中文摘要 背景 目前美國食品藥物管理局許可的急性缺血性中風的治療僅有在病發三小時內注射血栓溶解劑alteplase，然而大多數的病患由於抵達醫院求診的時間太晚而無法符合注射的條件。因此我們蒐集目前文獻資料庫裡除alteplase外、各種針對急性缺血性中風治療的隨機對照性試驗，並使用網絡統合性分析分析比較各種不同治療在於療效和危險性的差異。 研究方法 我們從三種電子資料庫包括MEDLINE、PubMED及Cochrane Central Register of Clinical Trials 進行系統性文獻回顧，藉以蒐集各種探討急性缺血性中風治療的隨機對照性試驗。蒐集的年限為西元2000年一月至西元2012年二月，探討的治療目標為經治療三個月後在修改過的雷氏量表(mRS)、美國國家衛生研究院腦中風量表(NIHSS)及巴氏量表(Barthel Index)上獲得明顯改善的人數以及治療後出現死亡或顱內出血的人數分析。 結果 系統性文獻回顧一共蒐集獲得十八篇研究結果，治療方式分為血管再灌流術和神經保護治療兩大類。以修改過的雷氏量表的結果分析，最佳療效為超音波血栓溶解術及局部低溫治療合併注射alteplase；效果最不顯著的治療則為注射tirofiban和紅血球生成素(erythropoietin)。在NIHSS方面，效果最佳的治療為DP-b99，較超音波血栓溶解術和局部低溫治療合併注射alteplase 兩者為佳。以巴氏量表的結果進行分析，最佳的治療則為局部低溫治療合併注射alteplase。治療後的死亡率以tirofiban和 DP-b99最低； 死亡率最高的治療則為desmoteplase 和紅血球生成素，其次為超音波血栓溶解術和局部低溫治療合併注射alteplase。顱內出血的發生率以注射白蛋白和雷射治療最低；最高則為超音波血栓溶解劑和局部低溫治療合併注射alteplase。若以各種治療目標進行統合性分析發現，對於神經功能復原最佳的治療則死亡率和顱內出血的比例都極高；反之死亡率和顱內出血機率較低的治療其神經功能預後往往不佳。僅有DP-b99、雷射治療和tenecteplase在於療效及危險性上獲得較佳的平衡性。 結論 目前探討的治療方式中並無治療同時擁有良好的療效及低危險性；神經保護治療適合單獨使用或合併其他療法目前角色也尚未明確，仍須進一步的研究探討，以期讓無法接受alteplase治療的急性缺血性中風患者獲得有效而安全的治療。

英文摘要 Background Alteplase is the only FDA-approved treatment for patients with acute ischemic stroke within 3 hours of onset; however, most of the patients are not qualified for the treatment due to late presentation. We did a network meta-analysis of randomized controlled trials to collect current available treatments, including recanalization and neuroprotection, for comparisons efficacy and treatment between different treatments. Materials and Methods We conducted a systematic review to collect randomized controlled trials of different treatment of acute ischemic stroke from electronic databases of MEDLINE, PubMED and Cochrane Central Register of Clinical Trials during January 2001 to February 2012. Outcomes for inclusion were mRS, NIHSS and Barthel Index after 3 months of treatment and incidences of mortality and ICH. Results A total of 18 studies were included in the review. In the outcome of mRS after 3 months of treatment, sonothrombolysis and focal hypothermia plus alteplase had the best beneficial effect for functional recovery. Tirofiban and erythromycin were the least beneficial treatment among all the treatments. DP-b99 is the best to reduce neurological deficits than sonothrombolysis and focal hypothermia plus alteplase evaluated by NIHSS. Focal hypothermia plus alteplase was better than other treatments by outcomes of Barthel Index. In risk of mortality, tirofiban and DP-b99 had the lowest risk of mortality while desmoteplase and erythromycin carried the highest risk of morality, which were followed by sonothrombolysis and focal hypothermia plus alteplase. In risk of ICH, treatment with sonothrombolysis and focal hypothermia plus alteplase had the highest risk, while treatment with albumin and laser therapy had the lowest risk. In the overall evaluation of different outcomes, treatments best in functional outcome had high risks of mortality and ICH; treatments in low risk of mortality and ICH showed little benefit in functional outcome. Only treatments with DP-b99, laser therapy and tenecteplase showed a moderate balance in efficacy and safety. Conclusion No treatment currently available for acute ischemic stroke except alteplase is both safe and efficacious. Whether neuroprotection should be used alone or combined with recanalization remained undetermined. Further investigation for the treatment of acute ischemic stroke is warranted in order to provide effective and safety treatment for those who are not qualified for alteplase.