A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage

Martini, Ross P.; Siler, Dominic A.; Cetas, Justin S.; Alkayed, Nabil J.; Allen, Elyse M.

doi:10.1007/s12028-021-01398-8

Cited by 23 publications

(16 citation statements)

References 27 publications

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“…Finally, a recent phase 1b clinical trial evaluated sEH inhibitor GSK2256294 and found the drug to be safe and well tolerated in critically ill patients with SAH. 172 GSK2256294 increased epoxyeicosatrienoates in serum, but not CSF, and it caused a trend for decreased CSF inflammatory cytokines. Although the study was not powered for efficacy, there was also a reduction in intensive care unit length of stay and hospital stay in patients treated with GSK2256294 as well as a trend towards an increased proportion of patients who were discharged to home.…”

Section: Inflammation In the Development Of DCImentioning

confidence: 95%

Role of Inflammatory Processes in Hemorrhagic Stroke

Ohashi

DeLong

Kozberg

et al. 2023

Stroke

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Hemorrhagic stroke is the deadliest form of stroke and includes the subtypes of intracerebral hemorrhage and subarachnoid hemorrhage. A common cause of hemorrhagic stroke in older individuals is cerebral amyloid angiopathy. Intracerebral hemorrhage and subarachnoid hemorrhage both lead to the rapid collection of blood in the central nervous system and generate inflammatory immune responses that involve both brain resident and infiltrating immune cells. These responses are complex and can contribute to both tissue recovery and tissue injury. Despite the interconnectedness of these major subtypes of hemorrhagic stroke, few reviews have discussed them collectively. The present review provides an update on inflammatory processes that occur in response to intracerebral hemorrhage and subarachnoid hemorrhage, and the role of inflammation in the pathophysiology of cerebral amyloid angiopathy–related hemorrhage. The goal is to highlight inflammatory processes that underlie disease pathology and recovery. We aim to discuss recent advances in our understanding of these conditions and identify gaps in knowledge with the potential to develop effective therapeutic strategies.

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Section: Inflammation In the Development Of DCImentioning

confidence: 95%

Role of Inflammatory Processes in Hemorrhagic Stroke

Ohashi

DeLong

Kozberg

et al. 2023

Stroke

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“… 46 The same inhibitor was found to be safe and raise serum EET levels compared to placebo in patients with aneurysmal subarachnoid hemorrhage. 47 Should our study findings be replicated in other cohorts, they would indicate that therapy using sEH inhibitors should likely be most beneficial to people at high risk of CVD. It would be interesting to explore if dietary intake of n6 fatty acids and background diet might influence downstream EET formation from arachidonic acid, as this would have the potential to improve CVD prevention in the general population.…”

Section: Discussionmentioning

confidence: 85%

Plasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study

et al. 2022

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“…No studies w identified that indicated a significant positive or negative impact of anti-inflammato therapy on the outcome endpoint of "death". [25][26][27][28][29][30][32][33][34][35][36][37][38]. Squares constitute the odds ratio; the bigger the square, the greater the weight given because of the narrower 95% CI.…”

Section: Impact Of Anti-inflammatory Therapy In Aneurysmal Sah On Sur...mentioning

confidence: 99%

Anti-Inflammatory Drug Therapy in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Prospective Randomized and Placebo-Controlled Trials

Wach

Vychopen

Güresir

et al. 2023

JCM

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Emerging evidence suggests that neuroinflammation may play a potential role in aneurysmal subarachnoid hemorrhage (aSAH). We aim to analyze the influence of anti-inflammatory therapy on survival and outcome in aSAH. Eligible randomized placebo-controlled prospective trials (RCTs) were searched in PubMed until March 2023. After screening the available studies for inclusion and exclusion criteria, we strictly extracted the main outcome measures. Dichotomous data were determined and extracted by odds ratio (OR) with 95% confidence intervals (CIs). Neurological outcome was graded using the modified Rankin Scale (mRS). We created funnel plots to analyze publication bias. From 967 articles identified during the initial screening, we included 14 RCTs in our meta-analysis. Our results illustrate that anti-inflammatory therapy yields an equivalent probability of survival compared to placebo or conventional management (OR: 0.81, 95% CI: 0.55–1.19, p = 0.28). Generally, anti-inflammatory therapy trended to be associated with a better neurologic outcome (mRS ≤ 2) compared to placebo or conventional treatment (OR: 1.48, 95% CI: 0.95–2.32, p = 0.08). Our meta-analysis showed no increased mortality form anti-inflammatory therapy. Anti-inflammatory therapy in aSAH patients tends to improve the neurological outcome. However, multicenter, rigorous, designed, prospective randomized studies are still needed to investigate the effect of fighting inflammation in improving neurological functioning after aSAH.

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A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage

Cited by 23 publications

References 27 publications

Role of Inflammatory Processes in Hemorrhagic Stroke

Role of Inflammatory Processes in Hemorrhagic Stroke

Plasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study

Anti-Inflammatory Drug Therapy in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Prospective Randomized and Placebo-Controlled Trials

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