Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update

Mervyn D I Vergouwen; Ale Algra; Gabriel J E Rinkel

doi:10.1161/STROKEAHA.112.666693

Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update

Mervyn D I Vergouwen^*
, Ale Algra
, Gabriel J E Rinkel

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2671-2176
Number of pages	6
Journal	Stroke
Volume	43
Issue number	10
DOIs	https://doi.org/10.1161/STROKEAHA.112.666693
Publication status	Published - Oct 2012

Keywords

Econometric and Statistical Methods: General
Geneeskunde(GENK)
Medical sciences
Bescherming en bevordering van de menselijke gezondheid

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10.1161/STROKEAHA.112.666693

vergouwen-et-al-2012-endothelin-receptor-antagonists-for-aneurysmal-subarachnoid-hemorrhageFinal published version, 976 KBLicence: Taverne

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@article{f6288a5dc3364e1db86d4dc3f8b7c289,

title = "Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update",

abstract = "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.",

keywords = "Econometric and Statistical Methods: General, Geneeskunde(GENK), Medical sciences, Bescherming en bevordering van de menselijke gezondheid",

author = "Vergouwen, \{Mervyn D I\} and Ale Algra and Rinkel, \{Gabriel J E\}",

year = "2012",

month = oct,

doi = "10.1161/STROKEAHA.112.666693",

language = "English",

volume = "43",

pages = "2671--2176",

journal = "Stroke",

issn = "0039-2499",

publisher = "Wolters Kluwer Health",

number = "10",

}

TY - JOUR

T1 - Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage

T2 - a systematic review and meta-analysis update

AU - Vergouwen, Mervyn D I

AU - Algra, Ale

AU - Rinkel, Gabriel J E

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - Econometric and Statistical Methods: General

KW - Geneeskunde(GENK)

KW - Medical sciences

KW - Bescherming en bevordering van de menselijke gezondheid

U2 - 10.1161/STROKEAHA.112.666693

DO - 10.1161/STROKEAHA.112.666693

M3 - Article

C2 - 22871682

SN - 0039-2499

VL - 43

SP - 2671

EP - 2176

JO - Stroke

JF - Stroke

IS - 10

ER -

Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update

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Keywords

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