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

Abstract

Delayed ischemic neurological deficits (DINDs) contribute to morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Based on promising preliminary reports, some clinicians routinely administer statins to prevent DINDs. Without language restriction, we searched MEDLINE, EMBASE, the Cochrane Central Register, references of review articles, proceedings of the International Stroke Conference, and gray literature sources. Studies were selected if they compared outcomes between statin-treated and untreated patients during the 2 weeks following SAH. Data were extracted and appraised independently and in duplicate, using standardized forms. Fixed or random effects models, as appropriate based on the degree of study heterogeneity, were applied to calculate summary measures. Four RCTs, two "pseudo" RCTs, five cohort studies, and one case-control study met eligibility criteria. In the RCTs, which enrolled a total of 309 patients, statins were found to significantly reduce the occurrence of DINDs [OR 0.38 (0.23-0.65); P < 0.001], but not mortality [OR 0.51 (0.25-1.02); P = 0.06] or poor neurological recovery [OR 0.81 (0.49-1.32); P = 0.39]. Observational studies assessed 1,542 patients, of whom 385 received statins. Statin-use was not associated with any reduction in DINDs [OR 0.96 (0.71-1.31); P = 0.80], mortality [OR 1.16 (0.78-1.73); P = 0.47] or poor neurological recovery [OR 1.20 (0.84-1.72); P = 0.31]. When the results of all studies were combined, statins had no statistically significant effect. 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.