Statins in the Management of Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis

Kramer, Andreas H.; Fletcher, Jeffrey J.

doi:10.1007/s12028-009-9306-9

Cited by 50 publications

(42 citation statements)

References 37 publications

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“…It is noteworthy that although not performed concurrently but examined in an identical SAH model, the effect size of MnTnHex-2-PyP exceeded that of simvastatin when treatment was begun postictus (e.g., after SAH MCA diameter increased by 24% with simvastatin versus 48% with MnTnHex-2-PyP) . Because simvastatin is clinically available and remains of interest for the treatment of clinical SAH (Kramer and Fletcher, 2010), direct comparison of these two pharmacologic interventions is warranted.…”

Section: Lipophilic Mnporphyrins In Experimental Mcao and Sah 913mentioning

confidence: 99%

Neuroprotective Efficacy from a Lipophilic Redox-Modulating Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: Rodent Models of Ischemic Stroke and Subarachnoid Hemorrhage

Sheng

Spasojević²,

Tse³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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Intracerebroventricular treatment with redox-regulating Mn(III) Nhexylpyridylporphyrin (MnPorphyrin) is remarkably efficacious in experimental central nervous system (CNS) injury. Clinical development has been arrested because of poor blood-brain barrier penetration. Mn(III) meso-tetrakis (N-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP) was synthesized to include four six-carbon (hexyl) side chains on the core MnPorphyrin structure. This has been shown to increase in vitro lipophilicity 13,500-fold relative to the hydrophilic ethyl analog Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP). In normal mice, we found brain MnTnHex-2-PyP accumulation to be ϳ9-fold greater than MnTE-2-PyP 24 h after a single intraperitoneal dose. We then evaluated MnTnHex-2-PyP efficacy in outcome-oriented models of focal cerebral ischemia and subarachnoid hemorrhage. For focal ischemia, rats underwent 90-min middle cerebral artery occlusion. Parenteral MnTnHex-2-PyP treatment began 5 min or 6 h after reperfusion onset and continued for 7 days. Neurologic function was improved with both early (P ϭ 0.002) and delayed (P ϭ 0.002) treatment onset. Total infarct size was decreased with both early (P ϭ 0.03) and delayed (P ϭ 0.01) treatment. MnTnHex-2-PyP attenuated nuclear factor B nuclear DNA binding activity and suppressed tumor necrosis factor-␣ and interleukin-6 expression. For subarachnoid hemorrhage, mice underwent perforation of the anterior cerebral artery and were treated with intraperitoneal MnTnHex-2-PyP or vehicle for 3 days. Neurologic function was improved (P ϭ 0.02), and vasoconstriction of the anterior cerebral (P ϭ 0.0005), middle cerebral (P ϭ 0.003), and internal carotid (P ϭ 0.015) arteries was decreased by MnTnHex-2-PyP. Side-chain elongation preserved MnPorphyrin redox activity, but improved CNS bioavailability sufficient to cause improved outcome from acute CNS injury, despite delay in parenteral treatment onset of up to 6 h. This advance now allows consideration of MnPorphyrins for treatment of cerebrovascular disease.

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Section: Lipophilic Mnporphyrins In Experimental Mcao and Sah 913mentioning

confidence: 99%

Neuroprotective Efficacy from a Lipophilic Redox-Modulating Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: Rodent Models of Ischemic Stroke and Subarachnoid Hemorrhage

Sheng

Spasojević²,

Tse³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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“…Clinical trials have, however, not demonstrated a consistent beneficial effect. A meta-analysis suggested that there may be a reduction in delayed cerebral ischemic (DCI) with statins, however, patients in these studies had a higher rate of DCI than typically reported elsewhere [40]. Another meta-analysis of 4 randomized trials showed no benefit with statin prophylaxis in Trans-Cranial Doppler (TCD) detected vasospasm, functional outcome, or mortality [41].…”

Section: Statinsmentioning

confidence: 99%

The Critical Care Management of Aneurysmal Subarachnoid Hemorrhage

Patel¹,

Samuels²

2012

Aneurysm

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“…Study results were inconsistent. A recent meta-analysis of the prospective studies demonstrated a small reduction in DCI and a small reduction in mortality, which was lost when patients from the non-peer-reviewed studies were included [94]. Another meta-analysis that included the 4 high-quality trials reported no benefit with regard to TCD-vasospasm, functional outcome, or mortality [95].…”

Section: Statinsmentioning

confidence: 99%

Treatment Options for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage

Athar

Levine

2012

Neurotherapeutics

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Statins in the Management of Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis

Abstract: Existing RCTs suggest that statins reduce DINDs, with a possible trend toward lower mortality. These findings are not supported by observational research. Although not assessed in all studies, current data do not indicate that statins improve neurological outcomes.

Cited by 50 publications

References 37 publications

Neuroprotective Efficacy from a Lipophilic Redox-Modulating Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: Rodent Models of Ischemic Stroke and Subarachnoid Hemorrhage

Neuroprotective Efficacy from a Lipophilic Redox-Modulating Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: Rodent Models of Ischemic Stroke and Subarachnoid Hemorrhage

The Critical Care Management of Aneurysmal Subarachnoid Hemorrhage

Treatment Options for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage

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