内皮素受体拮抗剂治疗颅内动脉瘤性蛛网膜下腔出血：系统评价和荟萃分析更新。
Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update.
机构信息
UMC Utrecht Stroke Center, Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
出版信息
Stroke. 2012 Oct;43(10):2671-6. doi: 10.1161/STROKEAHA.112.666693. Epub 2012 Aug 7.
BACKGROUND AND PURPOSE
Endothelin is considered to be a key mediator of vasospasm after subarachnoid hemorrhage. A meta-analysis of randomized trials on the effectiveness of endothelin receptor antagonists in subarachnoid hemorrhage has been published previously, but since then new major trials have been published. We present the results of a systematic review and meta-analysis update.
METHODS
We searched the Cochrane Library, the Cochrane Central Register of Controlled Trials, and PubMed with the following terms: subarachnoid hemorrhage AND (endothelin receptor antagonist OR clazosentan OR TAK-044 OR bosentan). All randomized, placebo-controlled trials investigating the effect of any endothelin receptor antagonists in patients with subarachnoid hemorrhage were included. Primary outcome was poor functional outcome (defined as death or dependency). Secondary outcomes were vasospasm, cerebral infarction as defined by investigators, and case fatality during follow-up. Data were pooled and effect sizes were expressed as risk ratio (RR) estimates with 95% confidence intervals (CI). We also calculated RR for several common complications.
RESULTS
in 5 trials with 2601 patients, endothelin receptor antagonists did not affect functional outcome (RR, 1.06: 95% CI, 0.93-1.22) despite a decreased incidence of angiographic vasospasm (RR, 0.58; 95% CI, 0.48-0.71). No effect was observed on vasospasm-related cerebral infarction (RR, 0.76; 95% CI, 0.53-1.11), any new cerebral infarction (RR, 1.04; 95% CI, 0.91-1.19), or case-fatality (RR, 1.04; 95% CI, 0.78-1.39). Endothelin receptor antagonists increased the risk of lung complications (RR, 1.79; 95% CI, 1.52-2.11), pulmonary edema (RR, 2.12; 95% CI, 1.32-3.39), hypotension (RR, 2.42: 95% CI, 1.78-3.29), and anemia (RR, 1.47; 95% CI, 1.19-1.83).
CONCLUSION
These results argue against the use of endothelin receptor antagonists in patients with subarachnoid hemorrhage.
背景与目的
内皮素被认为是蛛网膜下腔出血后血管痉挛的关键介质。先前已经发表了一项关于内皮素受体拮抗剂在蛛网膜下腔出血中有效性的随机试验的荟萃分析，但此后又发表了新的主要试验。我们呈现了系统评价和荟萃分析更新的结果。
方法
我们使用以下术语在 Cochrane 图书馆、Cochrane 对照试验中心注册库和 PubMed 进行了搜索：蛛网膜下腔出血和（内皮素受体拮抗剂或 clazosentan 或 TAK-044 或 bosentan）。所有纳入的随机、安慰剂对照试验均研究了内皮素受体拮抗剂在蛛网膜下腔出血患者中的作用。主要结局为不良功能结局（定义为死亡或依赖）。次要结局为血管痉挛、研究者定义的脑梗死和随访期间的病死率。数据汇总后，效应大小表示为风险比（RR）估计值及其 95%置信区间（CI）。我们还计算了几种常见并发症的 RR。
结果
在 5 项涉及 2601 名患者的试验中，内皮素受体拮抗剂并未影响功能结局（RR，1.06：95%CI，0.93-1.22），尽管血管造影血管痉挛的发生率降低（RR，0.58；95%CI，0.48-0.71）。血管痉挛相关脑梗死（RR，0.76；95%CI，0.53-1.11）、任何新发脑梗死（RR，1.04；95%CI，0.91-1.19）或病死率（RR，1.04；95%CI，0.78-1.39）均无影响。内皮素受体拮抗剂增加了肺并发症（RR，1.79；95%CI，1.52-2.11）、肺水肿（RR，2.12；95%CI，1.32-3.39）、低血压（RR，2.42；95%CI，1.78-3.29）和贫血（RR，1.47；95%CI，1.19-1.83）的风险。
结论
这些结果表明，内皮素受体拮抗剂不应用于蛛网膜下腔出血患者。
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