scholarly journals Effectiveness comparisons of drug therapies for postoperative aneurysmal subarachnoid hemorrhage patients: network meta‑analysis and systematic review

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wanli Yu ◽  
Yizhou Huang ◽  
Xiaolin Zhang ◽  
Huirong Luo ◽  
Weifu Chen ◽  
...  

Abstract Objective To compare the effectiveness of various drug interventions in improving the clinical outcome of postoperative patients after aneurysmal subarachnoid hemorrhage (aSAH) and assist in determining the drugs of definite curative effect in improving clinical prognosis. Methods Eligible Randomized Controlled Trials (RCTs) were searched in databases of PubMed, EMBASE, and Cochrane Library (inception to Sep 2020). Glasgow Outcome Scale (GOS) score, Extended Glasgow Outcome Scale (GOSE) score or modified Rankin Scale (mRS) score was used as the main outcome measurements to evaluate the efficacy of various drugs in improving the clinical outcomes of postoperative patients with aSAH. The network meta-analysis (NMA) was conducted based on a random-effects model, dichotomous variables were determined by using odds ratio (OR) with 95% confidence interval (CI), and a surface under the cumulative ranking curve (SUCRA) was generated to estimate the ranking probability of comparative effectiveness among different drug therapies. Results From the 493 of initial citation screening, forty-four RCTs (n = 10,626 participants) were eventually included in our analysis. Our NMA results showed that cilostazol (OR = 3.35,95%CI = 1.50,7.51) was the best intervention to improve the clinical outcome of patients (SUCRA = 87.29%, 95%CrI 0.07–0.46). Compared with the placebo group, only two drug interventions [nimodipine (OR = 1.61, 95%CI 1.01,2.57) and cilostazol (OR = 3.35, 95%CI 1.50, 7.51)] achieved significant statistical significance in improving the clinical outcome of patients. Conclusions Both nimodipine and cilostazol have exact curative effect to improve the outcome of postoperative patients with aSAH, and cilostazol may be the best drug to improve the outcome of patients after aSAH operation. Our study provides implications for future studies that, the combination of two or more drugs with relative safety and potential benefits (e.g., nimodipine and cilostazol) may improve the clinical outcome of patients more effectively.

2021 ◽  
Author(s):  
Wanli Yu ◽  
Yizhou Huang ◽  
Xiaolin Zhang ◽  
Huirong Luo ◽  
Weifu Chen ◽  
...  

Abstract Objective: To compare the effectiveness of various drug interventions in improving the clinical outcome of postoperative patients after aneurysmal subarachnoid hemorrhage (aSAH) and assist in determining the drugs of definite curative effect in improving clinical prognosis.Methods: Eligible Randomized Controlled Trials (RCTs) were searched in databases of PubMed, EMBASE, and Cochrane Library (inception to Sep 2020). Glasgow Outcome Scale (GOS) score, Extended Glasgow Outcome Scale (GOSE) score or modified Rankin Scale (mRS) score was used as the main outcome measurements to evaluate the efficacy of various drugs in improving the clinical outcomes of postoperative patients with aSAH. The network meta-analysis (NMA) was conducted based on a random-effects model, dichotomous variables were determined by using odds ratio (OR) with 95% confidence interval (CI), and a surface under the cumulative ranking curve (SUCRA) was generated to estimate the ranking probability of comparative effectiveness among different drug therapies.Results: From the 493 of initial citation screening, forty-four RCTs (n=10626 participants) were eventually included in our analysis. Our NMA results showed that cilostazol (OR=3.35,95%CI=1.50,7.51) was the best intervention to improve the clinical outcome of patients (SUCRA=87.29%, 95%CrI 0.07-0.46). Compared with the placebo group, only two drug interventions [nimodipine (OR=1.61, 95%CI 1.01,2.57) and cilostazol (OR=3.35, 95%CI 1.50, 7.51)] achieved significant statistical significance in improving the clinical outcome of patients. Conclusions: Both nimodipine and cilostazol have exact curative effect to improve the outcome of postoperative patients with aSAH, and cilostazol may be the best drug to improve the outcome of patients after aSAH operation. Our study provides implications for future studies that, the combination of two or more drugs with relative safety and potential benefits (e.g., nimodipine and cilostazol) may improve the clinical outcome of patients more effectively.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Gregoire Boulouis ◽  
Marc-Antoine Labeyrie ◽  
Jean Raymond ◽  
Christine Rodriguez-Regent ◽  
Anne-Claire Lukaszewicz ◽  
...  

Introduction: To report clinical outcome of aneurysmal subarachnoid hemorrhage (aSAH) patients exposed to cerebral vasospasm (CVS) targeted treatments in a systematic review and meta-analysis and compare the efficacy of endovascular and non-endovascular treatments in severe / refractory vasospasm patients. Methods: The literature was searched using PubMed, EMBASE, and The Cochrane Library database. Eligibility criteria were (1) Rated clinical outcome; (2) at least 10 patients; (3) aSAH; (4) study published in English or French (January 2006 - October 2014); and (5) methodological quality score > 10, according to STROBE criteria. Endpoint included unfavorable outcome rate, defined as mRS 3-6, GOS 1-3 or GOSE 1-4 at latest follow-up. Analyses included stratification per route of administration (oral, i.v., intra-arterial or cisternoventricular) and per study inclusion criteria (severe, CVS, refractory CVS or high risk for CVS). Univariate and multivariate subgroup analyses were performed to identify interventions associated with a better outcome. Results: Sixty-two studies, including 26 randomized controlled trials, were included (8976 patients). Overall 2490 patients had unfavorable outcome including death (random-effect weighted average: 33.7%, 99%CI, 28.1-39.7%; Q-value: 806.0, I 2 =92.7%). Clinical outcome was significantly better in severe or refractory patients for whom, on top of best medical treatment, endovascular intervention was performed (RR=0.76, IC95% [0.66-0.89], p <0.00001) whereas other route of administration didn’t show significant differences. RR of unfavorable outcome was significantly lower, vs control groups, in patients treated with Cilostazol (RR=0.46 (IC99% [0.25-0.85], P = 0.001, Q value 1.5, I 2 = 0). Conclusion: In case of CVS following aSAH, endovascular treatment in severe / refractory vasospasm patients. including intra-arterial injection of pharmacological agents or balloon angioplasty, improves outcome as compared to other route of administration.


2014 ◽  
Vol 120 (3) ◽  
pp. 605-611 ◽  
Author(s):  
Hieronymus D. Boogaarts ◽  
Martinus J. van Amerongen ◽  
Joost de Vries ◽  
Gert P. Westert ◽  
André L. M. Verbeek ◽  
...  

Object Increasing evidence exists that treatment of complex medical conditions in high-volume centers is found to improve outcome. Patients with subarachnoid hemorrhage (SAH), a complex disease, probably also benefit from treatment at a high-volume center. The authors aimed to determine, based on published literature, whether a higher hospital caseload is associated with improved outcomes of patients undergoing treatment after aneurysmal subarachnoid hemorrhage. Methods The authors identified studies from MEDLINE, Embase, and the Cochrane Library up to September 28, 2012, that evaluated outcome in high-volume versus low-volume centers in patients with SAH who were treated by either clipping or endovascular coiling. No language restrictions were set. The compared outcome measure was in-hospital mortality. Mortality in studies was pooled in a random effects meta-analysis. Study quality was reported according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Results Four articles were included in this analysis, representing 36,600 patients. The quality of studies was graded low in 3 and very low in 1. Meta-analysis using a random effects model showed a decrease in hospital mortality (OR 0.77 [95% CI 0.60–0.97]; p = 0.00; I2 = 91%) in high-volume hospitals treating SAH patients. Sensitivity analysis revealed the relative weight of the 1 low-quality study. Removal of the study with very low quality increased the effect size of the meta-analysis to an OR of 0.68 (95% CI 0.56–0.84; p = 0.00; I2 = 86%). The definition of hospital volume differed among studies. Cutoffs and dichotomizations were used as well as division in quartiles. In 1 study, low volume was defined as 9 or fewer patients yearly, whereas in another it was defined as fewer than 30 patients yearly. Similarly, 1 study defined high volume as more than 20 patients annually, and another defined it as more than 50 patients a year. For comparability between studies, recalculation was done with dichotomized data if available. Cross et al., 2003 (low volume ≤ 18, high volume ≥ 19) and Johnston, 2000 (low volume ≤ 31, high volume ≥ 32) provided core data for recalculation. The overall results of this analysis revealed an OR of 0.85 (95% CI 0.72–0.99; p = 0.00; I2 = 87%). Conclusions Despite the shortcomings of this study, the mortality rate was lower in hospitals with a larger caseload. Limitations of the meta-analysis are the not uniform cutoff values and uncertainty about case mix.


2017 ◽  
Vol 10 (4) ◽  
pp. 380-387 ◽  
Author(s):  
Anand Venkatraman ◽  
Ayaz M Khawaja ◽  
Sahil Gupta ◽  
Shalaka Hardas ◽  
John P Deveikis ◽  
...  

ObjectiveThe efficacy of intra-arterial vasodilators (IADs) for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains debatable. The objective of this meta-analysis was to pool estimates of angiographic and neurological response, clinical outcome, and mortality following treatment of vasospasm with IADs.MethodsWe searched PubMed, Embase, Scopus, Clinicaltrials.gov, Cochrane database, and CINAHL in December 2015 and August 2016. Studies reporting angiographic and neurological response, clinical outcome, and mortality following IAD treatment of vasospasm in 10 or more adults with aSAH were included. All established IADs were allowed. Two authors independently selected studies and abstracted the data. Mean weighted probabilities (MWP) were calculated using random effects model.ResultsInclusion criteria were met by 55 studies (n=1571). MWP for immediate angiographic response to IAD treatment was 89% (95% CI 83% to 94%), post-IAD neurological improvement 57% (95% CI 49% to 65%), good outcome 66% (95% CI 60% to 71%), and mortality was 9% (95% CI 7% to 12%). After adjusting for publication bias, MWP for mortality was 5% (95% CI 4% to 7%). When transcranial Doppler (TCD) was used along with clinical deterioration for patient selection, rates of neurological response (64%) and good outcome (72%) were better. IADs were not superior to controls (balloon angioplasty or medical management).ConclusionIAD treatment leads to a robust angiographic response and fair (but lower) rates of neurological response and good clinical outcome. Mortality was lower than the average reported in the literature. Rates of neurological response and good outcome were better when TCD was used for patient selection. Carefully designed studies are needed to compare IADs against medical management and balloon angioplasty.


2017 ◽  
Vol 127 (6) ◽  
pp. 1315-1325 ◽  
Author(s):  
Naif M. Alotaibi ◽  
Ghassan Awad Elkarim ◽  
Nardin Samuel ◽  
Oliver G. S. Ayling ◽  
Daipayan Guha ◽  
...  

OBJECTIVEPatients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) (World Federation of Neurosurgical Societies Grade IV or V) are often considered for decompressive craniectomy (DC) as a rescue therapy for refractory intracranial hypertension. The authors performed a systematic review and meta-analysis to assess the impact of DC on functional outcome and death in patients after poor-grade aSAH.METHODSA systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were identified through the Ovid Medline, Embase, Web of Science, and Cochrane Library databases from inception to October 2015. Only studies dedicated to patients with poor-grade aSAH were included. Primary outcomes were death and functional outcome assessed at any time period. Patients were grouped as having a favorable outcome (modified Rankin Scale [mRS] Scores 1–3, Glasgow Outcome Scale [GOS] Scores 4 and 5, extended Glasgow Outcome Scale [GOSE] Scores 5–8) or unfavorable outcome (mRS Scores 4–6, GOS Scores 1–3, GOSE Scores 1–4). Pooled estimates of event rates and odds ratios with 95% confidence intervals were calculated using the random-effects model.RESULTSFifteen studies encompassing 407 patients were included in the meta-analysis (all observational cohorts). The pooled event rate for poor outcome across all studies was 61.2% (95% CI 52%–69%) and for death was 27.8% (95% CI 21%–35%) at a median of 12 months after aSAH. Primary (or early) DC resulted in a lower overall event rate for unfavorable outcome than secondary (or delayed) DC (47.5% [95% CI 31%–64%] vs 74.4% [95% CI 43%–91%], respectively). Among studies with comparison groups, there was a trend toward a reduced mortality rate 1–3 months after discharge among patients who did not undergo DC (OR 0.58 [95% CI 0.27–1.25]; p = 0.168). However, this trend was not sustained at the 1-year follow-up (OR 1.09 [95% CI 0.55–2.13]; p = 0.79).CONCLUSIONSResults of this study summarize the best evidence available in the literature for DC in patients with poor-grade aSAH. DC is associated with high rates of unfavorable outcome and death. Because of the lack of robust control groups in a majority of the studies, the effect of DC on functional outcomes versus that of other interventions for refractory intracranial hypertension is still unknown. A randomized trial is needed.


Neurosurgery ◽  
2004 ◽  
Vol 54 (2) ◽  
pp. 326-335 ◽  
Author(s):  
Sepideh Amin-Hanjani ◽  
Christopher S. Ogilvy ◽  
Fred G. Barker

Abstract OBJECTIVE Despite existing strategies for the treatment of vasospasm after aneurysmal subarachnoid hemorrhage, vasospasm remains a persistent contributor to death and disability. The intracisternal application of thrombolytic agents to dissolve subarachnoid clot has been advocated. The goal of this analysis was to assess the currently available evidence regarding the effectiveness of this treatment. METHODS We conducted a systematic review of the published literature; all controlled trials were included. The outcomes of interest were delayed ischemic neurological deficits, poor Glasgow Outcome Scale scores, and death. A formal meta-analysis was performed with a random-effects model. RESULTS The search revealed nine trials or trial subgroups (only one of which was randomized), with a total enrollment of 652 patients. Pooled results demonstrated beneficial effects of treatment, with absolute risk reductions of 14.4% (95% confidence interval, 6.5–22.5%; P &lt; 0.001) for delayed ischemic neurological deficits, 9.5% (95% confidence interval, 4.2–14.8%; P &lt; 0.01) for poor Glasgow Outcome Scale scores, and 4.5% (95% confidence interval, 1.5–7.5%; P &lt; 0.05) for death. Regression analysis revealed that treatment effects did not significantly differ among the studies on the basis of the type of thrombolytic agent used (tissue plasminogen activator versus urokinase) or the method of administration (intraoperative versus postoperative) (P &gt; 0.10). Studies that enrolled only patients at high risk for vasospasm seemed to demonstrate greater treatment effects. CONCLUSION The meta-analysis suggests a clinically relevant and statistically significant beneficial effect of intracisternal thrombolysis. However, the results of the analysis are limited by the predominance of nonrandomized studies. Further randomized, blinded, placebo-controlled trials of high-risk patients would be justified.


2013 ◽  
Vol 119 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Jian Shen ◽  
Jian-Wei Pan ◽  
Zuo-Xu Fan ◽  
Xiao-Xing Xiong ◽  
Ren-Ya Zhan

Object Clazosentan therapy after aneurysmal subarachnoid hemorrhage (SAH) has been found to be effective in reducing the incidence of vasospasm in randomized controlled trials. However, while vasospasm-related morbidity, including delayed ischemic neurological deficits (DINDs) and delayed cerebral infarctions, was consistently decreased, statistical significance was not demonstrated and outcomes were not affected by clazosentan treatment. The objective of this meta-analysis was to determine whether clazosentan treatment after aneurysmal SAH significantly reduced the incidence of DINDs and delayed cerebral infarctions and improved outcomes. Methods All randomized controlled trials investigating the effect of clazosentan were retrieved via searches with sensitive and specific terms. Six variables were abstracted after the assessment of the methodological quality of the trials. Analyses were performed following the method guidelines of the Cochrane Back Review Group. Results Four randomized, placebo-controlled trials met eligibility criteria, enrolling a total of 2181 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk [RR] 0.76 [95% CI 0.62–0.92]) and delayed cerebral infarction (RR 0.79 [95% CI 0.63–1.00]) in patients treated with clazosentan after aneurysmal SAH. However, this treatment regimen was not shown to outcomes including functional outcomes measured by Glasgow Outcome Scale-Extended (RR 1.12 [95% CI 0.96–1.30]) or mortality (RR 1.02 [95%CI 0.70–1.49]). Adverse events, including pulmonary complications, anemia, and hypotension, were all significantly increased in patients who received clazosentan therapy. Conclusions The results of the present meta-analysis show that treatment with clazosentan after aneurysmal SAH significantly reduced the incidence of the vasospasm-related DINDs and delayed cerebral infarctions, but did not improve poor neurological outcomes in patients with aneurysmal SAH. Further study is required to elucidate the dissociation between vasospasm-related morbidity and outcomes.


2017 ◽  
Vol 126 (2) ◽  
pp. 586-595 ◽  
Author(s):  
Christopher D. Wilson ◽  
Sam Safavi-Abbasi ◽  
Hai Sun ◽  
M. Yashar S. Kalani ◽  
Yan D. Zhao ◽  
...  

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by hydrocephalus in 6.5%–67% of cases. Some patients with aSAH develop shunt dependency, which is often managed by ventriculoperitoneal shunt placement. The objectives of this study were to review published risk factors for shunt dependency in patients with aSAH, determine the level of evidence for each factor, and calculate the magnitude of each risk factor to better guide patient management. METHODS The authors searched PubMed and MEDLINE databases for Level A and Level B articles published through December 31, 2014, that describe factors affecting shunt dependency after aSAH and performed a systematic review and meta-analysis, stratifying the existing data according to level of evidence. RESULTS On the basis of the results of the meta-analysis, risk factors for shunt dependency included high Fisher grade (OR 7.74, 95% CI 4.47–13.41), acute hydrocephalus (OR 5.67, 95% CI 3.96–8.12), in-hospital complications (OR 4.91, 95% CI 2.79–8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80–5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51–4.21), rehemorrhage (OR 2.21, 95% CI 1.24–3.95), posterior circulation location of the aneurysm (OR 1.85, 95% CI 1.35–2.53), and age ≥ 60 years (OR 1.81, 95% CI 1.50–2.19). The only risk factor included in the meta-analysis that did not reach statistical significance was female sex (OR 1.13, 95% CI 0.77–1.65). CONCLUSIONS The authors identified several risk factors for shunt dependency in aSAH patients that help predict which patients are likely to require a permanent shunt. Although some of these risk factors are not independent of each other, this information assists clinicians in identifying at-risk patients and managing their treatment.


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