Andreas H Kramer1. 1. Departments of Critical Care Medicine and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 2T9, Canada. Andreas.Kramer@albertahealthservices.ca
Abstract
BACKGROUND: the pathophysiology of delayed neurological deficits (DNDs) following aneurysmal subarachnoid hemorrhage (SAH) is complex, and is not limited to arterial narrowing (vasospasm) and classical ischemia. Thus, combined drug approaches, or therapies with multiple effects, may have the greatest potential for benefit. Statins are known to have pleiotropic vascular effects, some of which may interrupt the pathogenesis of DNDs. Based on promising preliminary reports, many clinicians routinely administer statins to prevent DNDs. METHODS: a systematic review was performed to identify and summarize all animal research, observational studies, randomized controlled trials (RCTs) and meta-analyses which have evaluated the use of statins in the management of SAH. RESULTS: nine animal studies, nine observational (cohort and case-control) studies, six RCTs and three meta-analyses were identified. Animal studies have generally administered statin doses that, when adjusted for body weight, are 10-80 times larger than what is used in humans. Nevertheless, these models have consistently reported statins to reduce vasospasm and to demonstrate additional neuroprotective effects. However, observational studies have not revealed an association between statin-use and reduced DNDs or improved neurological outcomes. Results of RCTs have been inconsistent and limited by small sample size, but together suggest that statins may reduce DNDs, with no clear impact on mortality or neurological recovery. Optimal drug administration strategies (timing of initiation, most effective dose and duration) have not been clarified. CONCLUSIONS: the role of statins in the management of patients with SAH remains unclear. Although promising, statins should not, at this time, be considered standard care.
BACKGROUND: the pathophysiology of delayed neurological deficits (DNDs) following aneurysmal subarachnoid hemorrhage (SAH) is complex, and is not limited to arterial narrowing (vasospasm) and classical ischemia. Thus, combined drug approaches, or therapies with multiple effects, may have the greatest potential for benefit. Statins are known to have pleiotropic vascular effects, some of which may interrupt the pathogenesis of DNDs. Based on promising preliminary reports, many clinicians routinely administer statins to prevent DNDs. METHODS: a systematic review was performed to identify and summarize all animal research, observational studies, randomized controlled trials (RCTs) and meta-analyses which have evaluated the use of statins in the management of SAH. RESULTS: nine animal studies, nine observational (cohort and case-control) studies, six RCTs and three meta-analyses were identified. Animal studies have generally administered statin doses that, when adjusted for body weight, are 10-80 times larger than what is used in humans. Nevertheless, these models have consistently reported statins to reduce vasospasm and to demonstrate additional neuroprotective effects. However, observational studies have not revealed an association between statin-use and reduced DNDs or improved neurological outcomes. Results of RCTs have been inconsistent and limited by small sample size, but together suggest that statins may reduce DNDs, with no clear impact on mortality or neurological recovery. Optimal drug administration strategies (timing of initiation, most effective dose and duration) have not been clarified. CONCLUSIONS: the role of statins in the management of patients with SAH remains unclear. Although promising, statins should not, at this time, be considered standard care.