Longitudinal retinal changes in MOGAD

OBJECTIVE: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. METHODS: Eighty MOGAD patients and 139 healthy controls (HC) were included. OCT data was acquired with 1) Spectralis spectral domain OCT (MOGAD (N=66) and HC (N=103)) and 2) Cirrus HD-OCT (MOGAD (N=14) and HC (N=36)). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fibre layer (pRNFL) were quantified. RESULTS: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HC (p12 months ago (p<0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with HC. INTERPRETATION: Our study suggests the absence of attack-independent retinal damage in MOGAD. Yet, ongoing neuroaxonal damage or oedema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in MOGAD. This article is protected by copyright. All rights reserved

Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and meta-analysis

Background and purpose: Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with VKA-related ICH. Methods: We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC-related ICH in patients treated with and without NOAC-specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30–90 days following symptom onset. Results: Our literature search identified six eligible studies (four randomized controlled trials and two open-label trials of NOAC-specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36–0.58] with no heterogeneity (I 2 = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC-related and VKA-related (RR, 1.00; 95% CI, 0.84–1.19) ICH with no evidence of heterogeneity (I 2 = 0%). In the indirect analysis, the case fatality rate of NOAC-related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11–24%) vs. 41% (95% CI, 34–49%); P &amp;lt; 0.001]. Conclusions: Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH. © 2018 EA

Blood Pressure Reduction and Secondary Stroke Prevention

Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62-0.87; P&lt;0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59-0.85; P&lt;0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75-0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P&lt;0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention. © 2016 American Heart Association, Inc

Association of Ambulatory Blood Pressure Monitoring parameters with the Framingham Stroke Risk Profile

The Framingham Stroke Risk Profile (FSRP) is a novel and reliable tool for estimating the 10-year probability for incident stroke in stroke-free individuals, while the predictive value of ambulatory blood pressure monitoring (ABPM) for first-ever and recurrent stroke has been well established. We sought to evaluate cross-sectionally the association of ABPM parameters with FSRP score in a large sample of 2343 consecutive stroke-free individuals (mean age: 56.0 ± 12.9, 49.1% male) who underwent 24-hour ABPM. True hypertensives showed significantly higher FSRP (11.2 ± 5.0) compared to the normotensives (8.2 ± 5.0, p &amp;lt; 0.001), while subjects with white coat hypertension also had higher FSRP (10.2 ± 4.7) than normotensives (8.2 ± 5.0, p &amp;lt; 0.001). Compared to dippers that exhibited the lowest FSRP, non-dippers and reverse-dippers exhibited significantly higher FSRP (9.8 ± 4.8 for dippers vs 10.6 ± 5.2 and 11.5 ± 5.0 for non-dippers and reverse-dippers respectively, p ≤ 0.001 for comparisons). In univariate analyses, the ABPM parameters that had the strongest correlation with FSRP were 24-hour (r = 0.440, p &amp;lt; 0.001), daytime (r = 0.435, p &amp;lt; 0.001) and night-time (r = 0.423; p &amp;lt; 0.001) pulse pressure (PP). The best fitting model for predicting FSRP (R2 = 24.6%) on multiple linear regression analyses after adjustment for vascular risk factors not included in FSRP comprised the following parameters in descending order: 24-hour PP (β = 0.349, p &amp;lt; 0.001), daytime SBP variability (β = 0.124, p &amp;lt; 0.001), 24-hour HR variability (β = − 0.091, p &amp;lt; 0.001), mean 24-hour HR (β = − 0.107, p &amp;lt; 0.001), BMI (β = 0.081, p &amp;lt; 0.001) and dipping percentage (β = − 0.063, p = 0.001). 24-hour PP and daytime SBP variability are the two ABPM parameters that were more strongly associated with FSRP-score. Reverse dippers had the highest FSRP among all dipping status profiles. © 2017 Elsevier B.V

Association of elevated blood pressure levels with outcomes in acute ischemic stroke patients treated with intravenous thrombolysis: A systematic review and meta-analysis

Background and Purpose Although arbitrary blood pressure (BP) thresholds exist for acute ischemic stroke (AIS) patients eligible for intravenous thrombolysis (IVT), current international recommendations lack clarity on the impact of mean pre- and post-IVT BP levels on clinical outcomes. Methods Eligible studies involving IVT-treated AIS patients were identified that reported the association of mean systolic BP (SBP) or diastolic BP levels before and after IVT with the following outcomes: 3-month favorable functional outcome (modified Rankin Scale [mRS] scores of 0-1) and 3-month functional independence (mRS scores of 0-2), 3-month mortality and symptomatic intracranial hemorrhage (sICH). Unadjusted analyses of standardized mean differences and adjusted analyses of studies reporting odds ratios (ORadj) per 10 mm Hg BP increment were performed using random-effects models. Results We identified 26 studies comprising 56,513 patients. Higher pre- (P=0.02) and posttreatment (P=0.006) SBP levels were observed in patients with sICH. Patients with 3-month functional independence had lower post-treatment (P&amp;lt;0.001) SBP whereas trended towards lower pre-treatment (P=0.06) SBP. In adjusted analyses, elevated pre- (ORadj, 1.08; 95% confidence interval [CI], 1.01 to 1.16) and post-treatment (ORadj, 1.13; 95% CI, 1.01 to 1.25) SBP levels were associated with increased likelihood of sICH. Increasing pre- (ORadj, 0.91; 95% CI, 0.84 to 0.98) and post-treatment (ORadj, 0.70; 95% CI, 0.57 to 0.87) SBP values were also related to lower odds of 3-month functional independence. Conclusions We found that elevated BP levels adversely impact AIS outcomes in patients receiving IVT. Future randomized-controlled clinical trials will provide definitive data on the aforementioned association. © 2019 Korean Stroke Society

Percutaneous patent foramen ovale closure for secondary stroke prevention: Network meta-analysis

OBJECTIVE: Current guidelines report no benefit for patent foramen ovale (PFO) closure compared to medical treatment in patients with cryptogenic ischemic stroke (IS) or TIA. Two recent randomized controlled clinical trials have challenged these recommendations. METHODS: We performed a systematic review and network meta-analysis of randomized controlled trials to estimate the safety and efficacy of closure compared to medical treatment, and to compare available devices. We conducted pairwise meta-analyses for closure vs medical therapy, irrespective of the device used, and for each device vs medical therapy. RESULTS: Our literature search highlighted 6 studies. PFO occlusion was associated with reduced risk of recurrent IS (risk ratio [RR] 0.42, 95% confidence interval [CI] 0.20-0.91) and IS/TIA (RR 0.65, 95% CI 0.48-0.88) but with increased risk of new-onset atrial fibrillation (AF) (RR 4.59, 95% CI 2.01-10.45) compared to medical treatment. In indirect analyses, both Amplatzer (AMP) and GORE devices were found to be associated with a lower risk of new-onset AF compared to STARFlex (SFX) (RR 0.25, 95% CI 0.10-0.65 and RR 0.28, 95% CI 0.08-0.95). Moreover, AMP was found to be associated with a lower risk of recurrent IS/TIA events compared to the SFX device (RR 0.35, 95% CI 0.14-0.91). In the clustered ranking plot on the risk of IS against new-onset AF, GORE was comparable to AMP; however, on the risk of IS/TIA against new-onset AF, AMP appeared to be superior to the GORE device. In both ranking plots, SFX was highlighted as the worst option. CONCLUSION: PFO closure is associated with reduced risk of recurrent IS or IS/TIA and with increased risk of new-onset AF. © 2018 American Academy of Neurology

Novel oral anticoagulants for the secondary prevention of cerebral ischemia: A network meta-analysis

Background: Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin. Methods: Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome. Results: We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11-0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03-0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile. Conclusions: The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments. © The Author(s), 2016