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Serious hemorrhages after ischemic stroke or TIA - Incidence, mortality, and predictors
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.ORCID iD: 0000-0002-3542-7966
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0195324Article in journal (Refereed) Published
Abstract [en]

Background: Data are lacking on the risk and impact of a serious hemorrhage on the prognosis after ischemic stroke (IS) or transient ischemic attack (TIA). We aimed to estimate the incidence of serious hemorrhage, analyze the impact on mortality, and identify predictors of hemorrhage after discharge from IS or TIA.

Methods and findings: All patients admitted to Östersund Hospital for an IS or TIA in 2010–2013 were included (n = 1528, mean age: 75.1 years). Serious hemorrhages were identified until 31st December 2015. Incidence rates were calculated. The impact on mortality (stratified by functional level) was determined with Kaplan-Meier analysis. Non-parametric estimation under the assumption of competing risk was performed to assess the cumulative incidence and predictors of serious hemorrhages. The incidence rates of serious (n = 113) and intracranial hemorrhages (n = 45) after discharge from IS and TIA were 2.48% and 0.96% per year at risk, respectively. Patients with modified Rankin Scale (mRS) scores of 3–5 exhibited 58.9% mortality during follow-up and those with mRS scores of 0–2 exhibited 18.4% mortality. A serious hemorrhage did not affect mortality in patients with impaired functional status, but it increased the risk of death in patients with mRS scores of 0–2. Hypertension was associated with increased risk of serious hemorrhage.

Conclusions: We found that, after discharge from an IS or TIA, serious hemorrhages were fairly common. Impairments in function were associated with high mortality, but serious hemorrhages only increased the risk of mortality in patients with no or slight disability. Improved hypertension treatment may decrease the risk of serious hemorrhage, but in patients with low functional status, poor survival makes secondary prevention challenging.

Place, publisher, year, edition, pages
Public library science , 2018. Vol. 13, no 4, article id e0195324
National Category
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-147304DOI: 10.1371/journal.pone.0195324ISI: 000429206800061PubMedID: 29621285OAI: oai:DiVA.org:umu-147304DiVA, id: diva2:1210328
Available from: 2018-05-28 Created: 2018-05-28 Last updated: 2019-05-20Bibliographically approved
In thesis
1. Serious hemorrhage and secondary prevention after stroke and TIA
Open this publication in new window or tab >>Serious hemorrhage and secondary prevention after stroke and TIA
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The number of stroke survivors is growing worldwide, and these patients have an increased risk of new vascular events and death. This risk decreases with secondary treatment medications recommended in guidelines. However, the characteristics of unselected stroke patients differ from patients included in randomized controlled trials (RCTs). Thus, the efficacy of these treatments based on RCT results may not be directly transferable to the patients treated in clinical practice. A treatment may be associated with a higher risk of serious side-effects or less benefit than expected:1) Antithrombotic treatment increases the risk of a serious hemorrhage, a risk that is not well studied in an unselected population with older age and more comorbidities; 2) Treatment of modifiable risk factors after a stroke can be improved. Many patients do not reach treatment targets, which indicates a need for strategies to improve secondary prevention and increase treatment benefit.It is therefore essential to evaluate recommended treatments through studies in a real-world setting.

Aims: The aims of this thesis were to assessincidence, temporal trends, effect on mortality, and factors associated with an increased risk of a serious hemorrhage after ischemic stroke (IS) or transient ischemic attack (TIA); andif a nurse-led, telephone-based intervention including medical titration could improve modifiable risk factors in patients after stroke or TIA.

Methods: In paper I, all patients registered with an IS in the national stroke register Riksstroke during 1998–2009 were studied. The register was combined with the In-Patient Register and a diagnosis of intracranial haemorrhage (ICrH) within 1 year after IS was identified. In paper II, any diagnosis of serious hemorrhage was identified during follow-up up to 2015 in all patients with an IS or TIA diagnosis, 2010–2013, at Östersund hospital. The incidences of ICrH (papers I and II) and all serious hemorrhages (paper II) were calculated. Kaplan–Meier analysis was used to assess any temporal trend in paper I and if a serious hemorrhage affected survival in study II. Cox regression analysis was used in both studies I and II to assess any factor associated with hemorrhage.

In the randomized controlled NAILED stroke trial, all patients with acute stroke or TIA treated at Östersund hospital during 2010–2013 were screened for participation. Patients whose condition permitted a telephone-based follow-up were randomized to either a control group with follow-up according to usual care or to an intervention group with a nurse-led, telephone-based follow-up including titration of medication. Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) were assessed at 1, 12, 24, and 36 months. We assessed the effect of the intervention on mean levels of BP and LDL-C and on the proportion of patients reaching treatment targets at 12 months (Study III) and at 36 months (Study IV). Study III also assessed for interactions between group allocation and measurement levels at baseline with BP and LDL-C at the 12-month follow-up. Study IV also explored temporal trends.

Results: The risk of an ICrH was 1.97% per year at risk, within the first year after IS,  and 0.85% excluding the first 30 days. Between 1998 and 2009, the risk of an ICrH increased during the first 30 days after an IS but decreased during days 31–365. The risk of a serious hemorrhage was 2.48% per year at risk in paper II. It was more common in elderly. The incidence rate was higher in patients discharged with AP compared with RCTs. A hemorrhage increased the risk of death in patients with good functional status but did not affect the already high mortality in patients with impaired functional status. Male sex and previous ICrH were associated with an increased risk of ICrH during the first year after IS, thrombolytic treatment, atrial fibrillation and warfarin were associated with an increased risk in the acute phase. A previous diagnosis of hypertension was associated with an increased risk of all serious hemorrhages. 

The NAILED trial intervention group had a significantly lower mean systolic BP (SBP), diastolic BP (DBP), and LDL-C at 12 and 36 months. The mean SBP at 36 months was 128.1 mmHg (95% confidence interval (CI): 125.8–130.5) in the intervention group, 6.1 mmHg (95% CI: 3.6–8.6; p<0.001) lower than the control group. The interaction analysis at 12 months showed that the effect of the intervention was confined to patients whose values were above the respective targets at baseline and therefore had their medication adjusted. At 36 months, a significantly higher proportion of patients in the intervention group reached treatment targets for SBP, DBP, and LDL-C. The mean differences and differences in proportions reaching treatment target for BP increased during the 36 months of follow-up.

Conclusion: A serious hemorrhage after an IS or TIA is fairly common. It is more common in elderly and patients with impaired functional status. The incidence is higher in patients discharged with AP compared with RCTs. A serious hemorrhage could affect survival in patients with good functional status. The nurse-led, telephone-based intervention including medical titration used in the NAILED stroke trial improved risk factor levels after stroke and TIA, and more patients reached treatment targets. The effect increased over time. 

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2018. p. 63
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1997
Keywords
Stroke, transient ischemic attack, intracerebral hemorrhage, intracranial hemorrhage, serious haemorrhage, secondary prevention, modifiable risk factors, randomized controlled trial
National Category
Neurology
Research subject
Medicine, cardiovascular disease; Internal Medicine; Neurology
Identifiers
urn:nbn:se:umu:diva-153293 (URN)978-91-7601-982-5 (ISBN)
Public defence
2018-12-13, Hörsal Snäckan, Östersunds sjukhus, Östersund, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2018-11-22 Created: 2018-11-16 Last updated: 2018-11-20Bibliographically approved

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