Dataset Information

Impact of pre-stroke sulphonylurea and metformin use on mortality of intracerebral haemorrhage.

ABSTRACT:

Introduction

Few proven therapies for intracerebral haemorrhage exist. Preliminary observational evidence suggests that sulphonylurea and metformin may be protective in ischaemic stroke. We assessed the association of pre-intracerebral haemorrhage sulphonylurea and metformin use on outcome in diabetic patients.

Methods

We merged datasets from the consecutive single-centre Helsinki ICH Study, the intracerebral haemorrhage arm of the Virtual International Stroke Trials Archive (VISTA-ICH) and the Royal Melbourne Hospital ICH Study. Logistic regression adjusting for known predictors of intracerebral haemorrhage outcome (age, sex, baseline Glasgow Coma Scale, National Institutes of Health Stroke Scale, intracerebral haemorrhage volume, infratentorial location, intraventricular extension, and pre-intracerebral haemorrhage warfarin use) estimated the association of metformin and sulphonylurea with all-cause 90-day mortality.

Results

From a dataset of 2404 consecutive intracerebral haemorrhage patients, we included 374 (16%) patients with diabetes. Of these, 113 (30%) died by 90 days. Metformin was used in 148 (40%) patients and sulphonylurea in 115 (31%) patients at intracerebral haemorrhage onset. After adjusting for baseline characteristics, metformin use was associated with lower 90-day mortality (OR 0.51; 95% CI 0.26-0.97; p?=?0.041) irrespective of whether the drug was continued or not during the admission, while sulphonylurea use was not associated with mortality (OR 0.96; 95% CI 0.49-1.88; p?=?0.906). Haematoma location or evacuation did not modify the association between metformin and mortality; neither did adding insulin use, baseline glucose and serum creatinine into the model (OR 0.50; 95% CI 0.25-0.99; p?=?0.047).

Conclusion

Pre-intracerebral haemorrhage metformin use was associated with improved outcome in diabetic intracerebral haemorrhage patients. Our results generate hypotheses which after further validation could be tested in clinical trials.

SUBMITTER: Wu TY

PROVIDER: S-EPMC6301244 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

Impact of pre-stroke sulphonylurea and metformin use on mortality of intracerebral haemorrhage.

Wu Teddy Y TY Campbell Bruce Cv BC Strbian Daniel D Yassi Nawaf N Putaala Jukka J Tatlisumak Turgut T Davis Stephen M SM Meretoja Atte A

European stroke journal 20160826 4

<h4>Introduction</h4>Few proven therapies for intracerebral haemorrhage exist. Preliminary observational evidence suggests that sulphonylurea and metformin may be protective in ischaemic stroke. We assessed the association of pre-intracerebral haemorrhage sulphonylurea and metformin use on outcome in diabetic patients.<h4>Methods</h4>We merged datasets from the consecutive single-centre Helsinki ICH Study, the intracerebral haemorrhage arm of the Virtual International Stroke Trials Archive (VIST ...[more]

PMID: 31008292

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Project description:ObjectiveTo obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.MethodsWe conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.ResultsWe identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p?<?0.0001, I2?=?92%, p?<?0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p?<?0.00001; I2?=?42%, p?=?0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p?<?0.00001; I2?=?65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p?<?0.00001, I2?=?20%, p?=?0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p?<?0.00001, I2?=?71%, p?=?0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.ConclusionThis meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.

Project description:Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ?2/?4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of ? 1 APOE ?4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted.

Project description:BackgroundAnticipating the burden of intracerebral haemorrhage is crucial for proactive management and building resilience against future health challenges. Prior forecasts are based on population demography and to a lesser extent epidemiological trends. This study aims to utilise selected modifiable risk factors and socio-demographic indicators to forecast the incidence and mortality of intracerebral haemorrhage in Europe between 2019 and 2050.MethodsThree intracerebral haemorrhage risk factors identified in the Global Burden of Diseases, Injuries, and Risk Factors study (GBD 2019)-high systolic blood pressure, high fasting plasma glucose, and high body mass index-were utilised to predict the risk-attributable fractions between 2019 and 2050. Disease burden not attributable to these risk factors was then forecasted using time series models (autoregressive integrated moving average [ARIMA]), incorporating the Socio-demographic Index (SDI) as an external predictor. The optimal parameters of ARIMA models were selected for each age-sex-country group based on the Akaike Information Criterion (AIC). Different health scenarios were constructed by extending the past 85th and 15th percentiles of annualised rates of change in risk factors and SDI across all location-years, stratified by age and sex groups. A decomposition analysis was performed to assess the relative contributions of population size, age composition, and intracerebral haemorrhage risk on the projected changes.FindingsCompared with observed figures in 2019, our analysis predicts an increase in the burden of intracerebral haemorrhage in Europe in 2050, with a marginal rise of 0.6% (95% uncertainty interval [UI], -7.4% to 9.6%) in incident cases and an 8.9% (-2.8% to 23.6%) increase in mortality, reaching 141.2 (120.6-166.5) thousand and 144.2 (122.9-172.2) thousand respectively. These projections may fluctuate depending on trajectories of the risk factors and SDI; worsened trends could result in increases of 16.7% (8.7%-25.3%) in incidence and 31.2% (17.7%-48%) in mortality, while better trajectories may lead to a 10% (16.4%-2.3%) decrease in intracerebral haemorrhage cases with stabilised mortality. Individuals aged ≥80 years are expected to contribute significantly to the burden, comprising 62.7% of the cases in 2050, up from 40% in 2019, and 72.5% of deaths, up from 50.5%. Country-wide variations were noted in the projected changes, with decreases in the standardised rates across all nations but varying crude rates. The largest relative reductions in counts for both incidence and mortality are expected in Latvia, Bulgaria, and Hungary-ranging from -38.2% to -32.4% and -37.3% to -30.2% respectively. In contrast, the greatest increases for both measures were forecasted in Ireland (45.7% and 74.4%), Luxembourg (45% and 70.7%), and Cyprus (44.5% and 74.2%). The modelled increase in the burden of intracerebral haemorrhage could largely be attributed to population ageing.InterpretationThis study provides a comprehensive forecast of intracerebral haemorrhage in Europe until 2050, presenting different trajectories. The potential increase in the number of people experiencing and dying from intracerebral haemorrhage could have profound implications for both caregiving responsibilities and associated costs. However, forecasts were divergent between different scenarios and among EU countries, signalling the pivotal role of public health initiatives in steering the trajectories.FundingThe European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 754517. The National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research (NIHR202339).

Dataset Information

Impact of pre-stroke sulphonylurea and metformin use on mortality of intracerebral haemorrhage.

Introduction

Methods

Results

Conclusion

Publications

Impact of pre-stroke sulphonylurea and metformin use on mortality of intracerebral haemorrhage.

Similar Datasets

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