Prophylactic Therapies for Morbidity and Mortality After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Network Meta-Analysis of Randomized Trials

Abstract

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic treatments in patients with aneurysmal subarachnoid hemorrhage by performing a network meta-analysis of randomized trials. Methods: We searched Medline, Web of Science, Embase, Scopus, ProQuest, and Cochrane Central to February 2020. Pairs of reviewers independently identified eligible trials, extracted data, and assessed the risk of bias. Eligible trials compared the prophylactic effects of any oral or intravenous medications or intracranial drug-eluting implants to one another or placebo or standard of care in adult hospitalized patients with confirmed aneurysmal subarachnoid hemorrhage. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of the evidence. Results: We included 53 trials enrolling 10 415 patients. Nimodipine likely reduces all-cause mortality compared to placebo (odds ratio [OR],0.73 [95% CI, 0.53–1.00]; moderate certainty; absolute risk reduction (ARR), −3.35%). Nimodipine (OR, 1.46 [95% CI, 1.07–1.99]; high certainty; absolute risk increase, 8.25%) and cilostazol (OR, 3.73 [95% CI, 1.14–12.18]; moderate certainty; absolute risk increase, 23.15%) were the most effective treatments in improving disability at the longest follow-up. Compared to placebo, clazosentan (10 mg/kg; OR, 0.39 [95% CI, 0.22–0.68]; high certainty; ARR, −16.65%), nicardipine (OR, 0.48 [95% CI, 0.24–0.94]; moderate certainty; ARR, −13.70%), fasudil (OR, 0.55 [95% CI, 0.31–0.98]; moderate certainty; ARR, −11.54%), and magnesium (OR, 0.66 [95% CI, 0.46–0.94]; high certainty; ARR, −8.37%) proved most effective in reducing the likelihood of delayed cerebral ischemia. Conclusions: Nimodipine and cilostazol are likely the most effective treatments in preventing morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Clazosentan, nicardipine, fasudil, and magnesium showed beneficial effects on delayed cerebral ischemia and vasospasm but they were not found to reduce mortality or disability. Future trials are warranted to elaborately investigate the prophylactic effects of medications that may improve mortality and long-term functional outcomes, such as cilostazol and clazosentan. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42019122183.

Inflammatory Markers as Predictors of Shunt Dependency and Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage

“…Cerebral vasospasm and delayed cerebral ischemia (DCI) are major factors for survival and functional outcome following SAH and have, for many years, been the main focus in SAH research [ 42 , 43 , 44 , 45 ]. Clinical parameters such as Hunt and Hess scores, lower modified Fisher grade, the absence of intracerebral hematoma, intact pupillary light reflexes, and clinical improvement before aneurysm treatment can be used as early clinical predictors of functional outcome and favorable/non-favorable prognosis [ 46 ].…”

Prevalence of Subarachnoid Hemorrhage in Traumatic Brain Injury Patients: A Cross-Sectional Study

“…Subarachnoid hemorrhage is a serious disease with high morbidity and mortality. This disease affects about 30,000 to 40,000 people in the United States and 60,000 people in the world (12)(13)(14). Patients with SAH may suffer from various complications, such as systemic inflammation, myocardial damage, or cardiac dysfunction (15,16).…”

“…More than 30% of patients with SAH die within the first days to the first weeks after SAH. Also, if these patients survive, most of them suffer from cognitive disorders or disability (14,21). This disease has significant complications and mortality, and knowing the prognostic predictors and investigating related factors are of special importance.…”

Cervical sympathectomy to treat cerebral vasospasm: a scoping review

“…Clinical trials designed to treat CAV using mechanical or pharmacological vasodilation have failed to show an improvement in clinical outcome,5 6 and, at this time, oral nimodipine is the only class I and level of evidence A medication that has been shown to be an effective preventative treatment for DCI 7. A recent network metanalysis concluded that nimodipine and cilostazol are likely the most effective treatments in preventing morbidity and mortality in patients with aSAH 8. Interestingly, nimodipine does not reduce CAV, which suggests that this drug more likely inhibits cortical spreading ischemia and has fibrinolytic activity that reduces microthrombi 4 9.…”