Systolic blood pressure reduction strategies in acute ischemic stroke patients following endovascular thrombectomy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: There is no clear consensus on ideal systolic blood pressure (SBP) target post-endovascular thrombectomy (EVT) in patients with acute ischemic stroke. This study intends to investigate the relationship between reducing SBP and clinical outcomes and to determine the therapeutic efficacy of moderate and intensive SBP reduction post EVT. METHODS: A comprehensive search was conducted across five electronic databases to identify studies relevant to our analysis. Data from these studies were then analyzed using pooled relative risk (RR) along with their corresponding 95 % confidence intervals (CI) for our categorical outcomes. functional independence at 90 days post-EVT was defined as a modified Rankin score (mRS) 0-2. RESULTS: Our meta-analysis included eight studies with 2922 patients: 1376 patients were treated with intensive SBP reduction, 306 with moderate SBP reduction, and 1243 with standard SBP reduction. There was no difference in the risk of functional independence at 90 days post-EVT with both intensive-SBP reduction (target 120-140 mmHg, relative risk (RR) =1.05, 95 % CI 0.82, 1.34, p = 0.72) and moderate-SBP reduction (>160 mm Hg) (RR= 0.95, 95 % CI 0.69, 1.31, p = 0.76) compared with standard SBP reduction (>180 mm Hg). The risk of symptomatic intracranial hemorrhage (sICH) did not significantly differ between standard-SBP reduction and intensive-SBP reduction (RR = 0.93, 95 % CI 0.66, 1.31, p = 0.36) or moderate-SBP reduction (0.72 (95 % CI [0.28, 1.87], p = 0.50) groups, respectively. Intensive-SBP reduction significantly decreased the risk of hemicraniectomy. CONCLUSIONS: We did not identify any difference in functional independence at 90 days in acute ischemic stroke patients with either intensive-SBP reduction or moderate-SBP reduction compared with standard SBP reduction post-EVT.

The effectiveness and safety of clazosentan in treating aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of clazosentan, an endothelin receptor antagonist, in reducing CV, delayed cerebral ischemia (DCI), and the need for rescue therapy in aSAH patients, while evaluating its impact on functional outcomes and mortality. METHODS: We conducted a literature search across multiple databases to identify relevant studies evaluating the effects of clazosentan in aSAH patients. Both cohort studies and randomized controlled trials (RCTs) were included. The primary outcomes were vasospasm incidence, moderate to severe vasospasm, DCI, and the need for rescue therapy. Secondary outcomes included functional outcomes, mortality, and adverse events. The data were pooled as Risk ratios (R/R) with 95 % confidence intervals (CI) using RevMan 5.4 software. RESULTS: A total of 11 studies, including 10 published and one unpublished, comprising 8,469 patients were included in the meta-analysis. Clazosentan significantly reduced the incidence of vasospasm (R/R = 0.49: 0.34-0.70), moderate to severe vasospasm (R/R = 0.53: 0.46-0.61), DCI (R/R = 0.70: 0.59-0.82), and the need for rescue therapy (R/R = 0.65: 0.52-0.83) compared to placebo. However, no significant improvement in functional outcomes or mortality rates was observed. Clazosentan was associated with increased rates of pulmonary adverse events (R/R = 1.89: 1.64-2.18), hypotension (R/R = 2.47: 1.79-3.42), and anemia (R/R = 1.49: 1.23-1.79) but no increased risk of hepatobiliary adverse events or cerebral hemorrhage. CONCLUSIONS: Clazosentan demonstrates efficacy in reducing vasospasm, moderate to severe vasospasm, DCI, and the need for rescue therapy in aSAH patients, but does not significantly improve functional outcomes or mortality rates. While associated with specific adverse events, clazosentan may be a valuable adjunctive therapy in the management of aSAH, particularly in a high-risk population for vasospasm.

Efficacy and safety of argatroban in the management of acute ischemic stroke: A systematic literature review and meta-analysis.

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite intravenous thrombolysis and endovascular thrombectomy, a substantial number of patients do not achieve effective reperfusion. Argatroban, a direct thrombin inhibitor, can potentially improve neurological outcomes in AIS patients. However, there are conflicting results in the medical literature regarding the efficacy and safety of argatroban in this context. OBJECTIVE: This study aims to evaluate the efficacy and safety of argatroban as monotherapy or adjunct therapy for acute ischemic stroke. METHODS: Five major databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of using argatroban alone or in combination with recombinant tissue plasminogen activator (r-TPA) in the management protocol of the AIS. We used Review Manager Software (RevMan 5.4.1) for data analysis. RESULTS: We included 1393 patients from eight RCTs (of them, 726 were treated with argatroban alone or combined with r-TPA, while 667 received the placebo, standard therapy (standard treatments based on current guidelines including antihypertensive, antiplatelet agents, and statins) or endovascular r-TPA). Neither argatroban vs control nor argatroban with r-TPA vs r-TPA showed significant difference regarding the activity in daily living; (SMD= 1.69, 95% CI [-0.23, 3.61]; p = 0.09), (SMD= 0.99, 95% CI [-0.88, 2.86]; p = 0.30), respectively. Also, there was no significant difference in the National Institutes of Health Stroke Scale (NIHSS) score at seven days, the number of patients achieving modified Rankin Scale (mRS) of 0-1 or 0-2 at 90 days (p > 0.05). Argatroban did not significantly increase the risk of adverse events or symptomatic intracranial hemorrhage (ICH), or major systemic bleeding compared to control or r-TPA (p > 0.05) CONCLUSIONS: Argatroban does not demonstrate superior efficacy compared to placebo or standard therapy in terms of ADL, NIHSS and mRS outcomes. Importantly, argatroban does not significantly increase the incidence of adverse events, including symptomatic ICH and systemic bleeding.

Clinical Characteristics as Predictors of Early and Delayed Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage Patients: A Meta-Analysis of 4527 Cases.

BACKGROUND: Predictors of delayed cerebral infarction (DCI) and early cerebral infraction (ECI) among aneurysmal subarachnoid hemorrhage (aSAH) patients remain unclear. We aimed to systematically review and synthesize the literature on predictors of ECI and DCI among aSAH patients. METHODS: We systematically searched PubMed, EMBASE, Cochrane Library, and Scopus databases comprehensively from inception through January 2024 for observational cohort studies examining predictors of DCI or ECI following aneurysmal SAH. Studies were screened, reviewed, and meta-analyzed, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines. The data were pooled as Odds ratios (OR) with 95% confidence intervals using Review Manager 5.4 software. Methodologic quality was assessed with the Newcastle-Ottawa Scale. RESULTS: Our meta-analysis included 12 moderate to high-quality cohort studies comprising 4527 patients. Regarding DCI predictors, Higher severity scores (OR = 1.49, 95% confidence interval [1.12, 1.97], P = 0.005) and high Fisher scores (OR = 2.23, 95% confidence interval [1.28, 3.89], P = 0.005) on presentation were significantly associated with an increased risk of DCI. Also, the female sex and the presence of vasospasm were significantly associated with an increased risk of DCI (OR = 3.04, 95% confidence interval [1.35, 6.88], P = 0.007). In contrast, preexisting hypertension (P = 0.94), aneurysm treatment (P = 0.14), and location (P = 0.16) did not reliably predict DCI risk. Regarding ECI, the pooled analysis demonstrated no significant associations between sex (P = 0.51), pre-existing hypertension (P = 0.63), severity (P = 0.51), or anterior aneurysm location versus posterior (P = 0.86) and the occurrence of ECI. CONCLUSION: Female sex, admission disease severity, presence of vasospasm and Fisher grading can predict DCI risk post-aSAH. Significant knowledge gaps exist for ECI predictors. Further large standardized cohorts are warranted to guide prognosis and interventions.

Ticagrelor Versus Clopidogrel in Endovascular Therapy for Cerebral Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Antiplatelet therapy is pivotal in endovascular treatment for intracranial aneurysms. However, there is a lack of studies comparing ticagrelor to clopidogrel in patients with aneurysms undergoing endovascular therapy. Additionally, the existing literature lacks adequate sample size, significant subgrouping, and follow-up, making our study important to cover these gaps. METHODS: We searched 5 databases to collect all relevant studies. Categorical outcomes were pooled as relative risk (R.R.) with a 95% confidence interval (CI). In the single-arm meta-analysis, outcomes were pooled as proportions and their corresponding 95% CI. RESULTS: This comprehensive analysis of 18 studies involving 2,427 patients. For thromboembolic events, the pooled (R.R.) did not show significant differences, whether considering overall events. A similar pattern was observed for thromboembolic events stratified by aneurysmal rupture status, with no significant differences in overall events. Hemorrhagic events did not also exhibit significant differences in previously mentioned stratifications. Furthermore, there were no substantial differences in death and mRS (0-2) on discharge between Ticagrelor and Clopidogrel. Single-arm meta-analyses for Ticagrelor demonstrated low rates of thromboembolic events, hemorrhage, death, and favorable mRS scores, with associated confidence intervals (CIs). Main line of endovascular treatment did not significantly affect either thromboembolic or hemorrhagic outcomes with Ticagrelor and Clopidogrel. CONCLUSIONS: We found no significant differences in key outcomes like thromboembolic events, hemorrhagic events, mortality rates, and favorable mRS (0-2) upon discharge in the studied patients between Ticagrelor and Clopidogrel. Moreover, the single-arm meta-analysis for Ticagrelor revealed low rates of thromboembolic events, hemorrhage, mortality, and high rates of favorable mRS scores.