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  • 1
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    Multiple Silent Lacunes Are Associated with Recurrent Ischemic Stroke
    S. Karger AG ; 2016
    In:  Cerebrovascular Diseases Vol. 42, No. 1-2 ( 2016), p. 73-80
    Details
    In: Cerebrovascular Diseases, S. Karger AG, Vol. 42, No. 1-2 ( 2016), p. 73-80
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Silent lacunes are a common finding on brain imaging in ischemic stroke patients, but the prognostic significance of these lesions is uncertain. We aimed at investigating the association of silent lacunes and the risk of ischemic stroke recurrence, death, and cardiovascular events in a cohort of patients with incident ischemic stroke and no atrial fibrillation (AF). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We included 786 patients (mean age 59.5 (SD 14.0); 42.9% females) in a registry-based, observational cohort study on patients with first-ever ischemic stroke. On brain MRI we assessed the number of silent lacunes as none, single, or multiple and we calculated stratified incidence rates of the outcomes. Cox proportional hazard ratios (HRs) adjusted for age, gender, congestive heart failure, hypertension, diabetes, and vascular disease were calculated with no silent lacunes as reference. In additional analyses, we further adjusted for white matter hyperintensities. Patients were followed up until death or recurrence of ischemic stroke. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 In 81 (10.3%) patients, a single silent lacune was present, and in 87 (11.1%) patients, multiple silent lacunes were present. Patients with at least one silent lacune were older (mean age 66.1 vs. 57.7, p 〈 0.001) and were more often hypertensive (60.1 vs. 43.4%, p 〈 0.001) compared to patients with no silent lacunes. During a median follow-up time of 2.9 (interquartile range 3.1) years, we observed 53 recurrent ischemic strokes, 76 deaths, and 96 cardiovascular events. Incidence rates per 100 person-years of ischemic stroke recurrence were 1.6, 2.5, and 5.0 for none, single, and multiple silent lacunes respectively. Corresponding incidence rates were 2.6, 2.4, and 4.4 for death, and 3.4, 4.0, and 6.6 for cardiovascular events respectively. Adjusted HRs of ischemic stroke recurrence were 1.53 (0.67-3.49) and 2.52 (1.25-5.09) for a single and multiple silent lacunes, respectively. Further adjustment for white matter hyperintensities maintained positive association although not significant. Corresponding adjusted HRs were 0.56 (0.25-1.25) and 0.65 (0.33-1.25) for death and 1.16 (0.61-2.22) and 1.51 (0.86-2.66) for cardiovascular events. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 In this large cohort of patients with incident ischemic stroke and no AF, an increasing number of silent lacunes was associated with increasing incidence rates of ischemic stroke recurrence. In the adjusted Cox proportional hazard analyses, the presence of multiple silent lacunes was significantly associated with an increased risk of ischemic stroke recurrence. The risk of death or cardiovascular events was not significantly influenced by the presence of silent lacunes.
    Type of Medium: Online Resource
    ISSN: 1015-9770 , 1421-9786
    URL: Article
    DOI: 10.1159/000445196
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
    detail.hit.zdb_id: 1482069-9
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  • 2
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    Adverse Events and All-Cause Mortality in Danish Patients with Cerebral Venous Thrombosis: A Nationwide Cohort Study
    Georg Thieme Verlag KG ; 2022
    In:  Thrombosis and Haemostasis Vol. 122, No. 09 ( 2022-09), p. 1524-1531
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 122, No. 09 ( 2022-09), p. 1524-1531
    Abstract: Background Cerebral venous thrombosis (CVT) is a rare manifestation of stroke and venous thromboembolism (VTE), compared with deep vein thrombosis (DVT) and pulmonary embolism (PE). We examined whether CVT was associated with adverse cardiovascular events. Methods A Danish cohort study with adult patients diagnosed with CVT (N = 1,015) between 1997 and 2017. We matched 10 patients with VTE (DVT and PE) to each patient with CVT for age, sex, and diagnosis year. We also matched 10 individuals from the general population to each patient with CVT. We computed cumulative incidence and estimated hazard ratios (HRs) with 95% confidence intervals (95% CIs) at 5 years for major bleeding, intracranial bleeding, ischemic stroke, and cardiovascular events. Death was examined separately. Results Major bleeding risks were 1.2% for CVT and 0.7% for VTE at 6 months; these risks increased to 2.7% and 2.6%, respectively, at 5 years. Although rare, intracranial bleeding risks were markedly higher for CVT (2.9%) than for VTE (0.4%) at 5 years (HR = 8.9, 95% CI: 5.3–15.1). Incidences of ischemic stroke were 5.9% for CVT and 0.3% for VTE, at 6 months; and 10.0% and 1.4%, respectively, at 5 years (HR = 9.5, 95% CI: 7.1–12.7). In contrast, incidence of cardiac events was lower for CVT that VTE (1.7% vs. 3.6% at 5 years). Mortality risk was higher after CVT compared with VTE, at 6 months (6.6% vs. 3.8%), but the risks differed little at 5 years (14.3% vs. 14.1%). Conclusion Intracranial bleeding, ischemic stroke, and mortality risks were higher for patients with CVT than matched patients with VTE and the general population, particularly within 6 months after diagnosis.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1055/s-0042-1743473
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2022
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  • 3
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    Effectiveness of self-managed oral anticoagulant therapy in patients with recurrent venous thromboembolism : A propensity-matched cohort study
    Georg Thieme Verlag KG ; 2016
    In:  Thrombosis and Haemostasis Vol. 116, No. 09 ( 2016), p. 524-529
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 116, No. 09 ( 2016), p. 524-529
    Abstract: Patient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross-linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42–0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44–2.02). The risk of all-cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21–0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00–1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency. Supplementary Material to this article is available online at www.thrombosis-online.com.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1160/TH16-02-0088
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2016
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  • 4
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    Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation : An indirect comparison analysis
    Georg Thieme Verlag KG ; 2014
    In:  Thrombosis and Haemostasis Vol. 112, No. 05 ( 2014), p. 981-988
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 112, No. 05 ( 2014), p. 981-988
    Abstract: Large Phase 3 clinical trials for stroke prevention in atrial fibrillation (AF) have compared non-vitamin K antagonist oral anticoagulants (NOACs) against warfarin, with the edoxaban trial only recently reported. In the absence of head to head trials directly comparing these NOACs against each other, we compared the efficacy and safety of edoxaban to other agents by an indirect comparison analysis. We performed an indirect comparison analysis of edoxaban (2 dose strategies) against apixaban (1 dose), dabigatran etexilate (2 doses) and rivaroxaban (1 dose), for their relative efficacy and safety against each other. For high-dose edoxaban vs apixaban, there were no significant differences in efficacy endpoints, mortality, myocardial infarction and major bleeding. Apixaban was associated with less major or clinically relevant non-major bleeding (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70–0.90) and gastrointestinal bleeding (HR 0.72; 95% CI 0.53–0.99). For dabigatran 110 mg twice daily, there were no significant differences in the main efficacy or safety endpoints. Dabigatran 150 mg bid was associated with lower stroke/systemic embolism (SE) (HR 0.75; 95% CI 0.56–0.99), stroke (HR 0.73; 95% CI 0.55–0.96) and haemorrhagic stroke (HR 0.48; 95% CI 0.23–0.99). There were no significant differences between high-dose edoxaban vs rivaroxaban for efficacy endpoints or mortality, but rivaroxaban had more major and/or clinically relevant non-major bleeding. When compared to low-dose edoxaban, apixaban was associated with lower stroke/SE (HR 0.70; 95% CI 0.55–0.89), stroke (HR 0.70; 95% CI 0.55–0.92) and ischaemic stroke (HR 0.65; 95% CI 0.50–0.89), but more major bleeding (HR 1.47; 95% CI 1.20–1.80). For dabigatran 110 mg bid, there were no significant differences in the efficacy endpoints, but dabigatran 110 mg bid had higher major (and gastrointestinal) bleeding. Dabigatran 150 mg bid and rivaroxaban were associated with lower stroke/SE and ischaemic stroke, but higher bleeding rates. In the present analysis, we have provided for the first time, comparisons of efficacy and safety of edoxaban against other NOACs. Notwithstanding the significant limitations of an indirect comparison analysis, some differential effects are evident with the NOACs for stroke prevention, allowing us to allow the prescriber a ‘choice’ to be able to fit the drug to the patient clinical profile (and vice versa). Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1160/TH14-02-0118
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2014
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  • 5
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    Edoxaban versus placebo, aspirin, or aspirin plus clopidogrel for stroke prevention in atrial fibrillation : An indirect comparison analysis
    Georg Thieme Verlag KG ; 2015
    In:  Thrombosis and Haemostasis Vol. 114, No. 08 ( 2015), p. 403-409
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 114, No. 08 ( 2015), p. 403-409
    Abstract: As non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In ‘real world’ clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p 〈 0.01) when modeled to data from a ‘real world’ cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on ‘real world’ data. Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1160/TH15-05-0383
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2015
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  • 6
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    Duration of Diabetes Mellitus and Risk of Thromboembolism and Bleeding in Atrial Fibrillation : Nationwide Cohort Study
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Stroke Vol. 46, No. 8 ( 2015-08), p. 2168-2174
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 8 ( 2015-08), p. 2168-2174
    Abstract: Guidelines advocate anticoagulant treatment to all patients with atrial fibrillation and concomitant diabetes mellitus. The potential refinement to thromboembolic risk stratification that may spring from subdividing diabetes mellitus is unexplored. The purpose was to investigate duration of diabetes mellitus as a predictor of thromboembolism and anticoagulant-related bleeding in patients with atrial fibrillation. Methods— Using nationwide Danish registries, we identified all patients discharged from hospital with an incident diagnosis of atrial fibrillation from 2000 to 2011. Hazard ratios with 95% confidence intervals for thromboembolism and bleeding according to years of diabetes mellitus duration in categories (0–4, 5–9, 10–14, and ≥15) and as a continuous variable using cubic splines were calculated by Cox regression. Results— The study population comprised 137 222 patients with atrial fibrillation, of which 12.4% had diabetes mellitus. Compared with patients without diabetes mellitus and after adjustment for anticoagulant treatment and CHA 2 DS 2 -VASc components (congestive heart failure, hypertension, age, previous stroke, vascular disease, and sex), the risk of thromboembolism was lowest in the 0 to 4 years duration category (hazard ratio, 1.11; 95% confidence interval, 1.03–1.20), and highest in the longest duration category of ≥15 years (hazard ratio, 1.48; 95% confidence interval, 1.29–1.70). When analyzed as a continuous variable, duration of diabetes mellitus was associated with risk of thromboembolism in a dose-response-dependent manner, but not with a higher risk of bleeding during anticoagulant treatment. Conclusions— In patients with atrial fibrillation, longer duration of diabetes mellitus was associated with a higher risk of thromboembolism, but not with a higher risk of anticoagulant-related bleeding. Considering the critical balance between preventing thromboembolism and avoiding bleeding, longer duration of diabetes mellitus may favor initiation of anticoagulant therapy.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.115.009371
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467823-8
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  • 7
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    Effect of Anticoagulation on Hospitalization Costs After Intracranial Hemorrhage in Atrial Fibrillation : A Registry Study
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Stroke Vol. 47, No. 4 ( 2016-04), p. 979-985
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 4 ( 2016-04), p. 979-985
    Abstract: Intracranial hemorrhage (ICH) is the most feared adverse event with oral anticoagulant therapy in patients with atrial fibrillation. The health economic aspects of resuming oral anticoagulant therapy after ICH are unknown. The aim was to estimate hospitalization costs of thromboembolism and hemorrhage subsequent to ICH in 2 patient groups with atrial fibrillation surviving the first 90 days post ICH: (1) patients resuming warfarin therapy within 90 days post ICH and (2) patients discontinuing therapy. Methods— Retrospective data from Danish national registries were linked to identify patients with atrial fibrillation who suffered an ICH between January 1, 1997, and April 1, 2011. Study start was 90 days after incident ICH. Mortality was evaluated using the Kaplan–Meier estimate. Occurrence of hospitalization-requiring thromboembolism and hemorrhage was used to estimate hospitalization costs by linkage of International Classification of Diseases , Tenth Revision, codes to Danish Diagnosis–Related Group tariffs. The effect of resuming warfarin therapy on average 3-year hospitalization costs was estimated by regression analysis adjusted for between-group differences in baseline characteristics. Results— In the inclusion period, 2162 patients had an ICH; 1098 survived the first 90 days and were included for analysis, and of those, 267 resumed warfarin therapy. Therapy resumption reduced the mean 3-year hospitalization cost of hospitalized patients significantly by US$ 1588 (95% confidence interval, −2925 to −251) and was significantly correlated with fewer hospitalization days per hospitalized patient (−4.6 [95% confidence interval, −7.6 to −1.6]). The marginal effect of therapy resumption on hospitalization costs per patient was US$ −407 (95% confidence interval, −815 to 2). Conclusions— Resuming warfarin therapy within 90 days after ICH in patients with atrial fibrillation is associated with a decrease in average hospitalization costs.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.115.012338
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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  • 8
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    Non–Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients With Intracerebral Hemorrhage
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Stroke Vol. 50, No. 4 ( 2019-04), p. 939-946
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 4 ( 2019-04), p. 939-946
    Abstract: Recurrent bleeding associated with oral anticoagulants (OACs) causes a dilemma in patients with atrial fibrillation (AF) sustaining an intracerebral hemorrhage. Treatment recommendations guiding clinical practice on optimal OAC agent selection in this population are lacking. This study aimed to investigate the comparative effectiveness and safety of non–vitamin K antagonist OAC (NOAC) versus warfarin in patients with AF sustaining an intracerebral hemorrhage. Methods— We conducted a nationwide observational cohort study including patients with AF sustaining an intracerebral hemorrhage and who subsequently claimed an OAC prescription. Contrasts of 1-year risks for ischemic stroke and intracerebral hemorrhage risks were obtained and evaluated by inverse probability treatment weighted absolute risk reduction and risk ratios. Results— Among 622 AF patients with intracerebral hemorrhage, 274 claimed a warfarin prescription and 348 a NOAC prescription. Mean age was 76 years (39% females); 72% had an index nonsevere event and 28% moderate to severe index event according to the Scandinavian Stroke Severity scale. The 1-year ischemic stroke risk was 7.85% for warfarin and 4.01% for NOACs, with a weighted absolute risk reduction of 3.78% (95% CI, −0.15% to 7.71%); the weighted risk ratio was 0.52 (0.27–1.00). For recurrent intracerebral hemorrhage, the risk was 7.00% for warfarin and 5.07% for NOACs. The absolute risk reduction was 1.93% (−2.02% to 5.87%), with an a weighted risk ratio of 0.72 (0.38–1.38). Conclusions— NOACs were associated with a nonsignificant lower risk of ischemic stroke and recurrent intracerebral hemorrhage compared with warfarin. The results add to current recommendations of selecting a NOAC agent for stroke prophylaxis treatment in patients with AF, including those with sustaining an intracerebral hemorrhage.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.118.023797
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467823-8
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  • 9
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    Stroke and bleeding risk scores in patients with atrial fibrillation and valvular heart disease: evaluating ‘valvular heart disease’ in a nationwide cohort study
    Oxford University Press (OUP) ; 2019
    In:  EP Europace Vol. 21, No. 1 ( 2019-01-01), p. 33-40
    Details
    In: EP Europace, Oxford University Press (OUP), Vol. 21, No. 1 ( 2019-01-01), p. 33-40
    Type of Medium: Online Resource
    ISSN: 1099-5129 , 1532-2092
    URL: Article
    DOI: 10.1093/europace/euy151
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2002579-8
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  • 10
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    Evaluation of the C2HEST Risk Score as a Possible Opportunistic Screening Tool for Incident Atrial Fibrillation in a Healthy Population (From a Nationwide Danish Cohort Study)
    Elsevier BV ; 2020
    In:  The American Journal of Cardiology Vol. 125, No. 1 ( 2020-01), p. 48-54
    Details
    In: The American Journal of Cardiology, Elsevier BV, Vol. 125, No. 1 ( 2020-01), p. 48-54
    Type of Medium: Online Resource
    ISSN: 0002-9149
    URL: Article
    DOI: 10.1016/j.amjcard.2019.09.034
    RVK:
    XA 18500
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2019595-3
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