Risk of Recurrent Venous Thromboembolism: A Danish Nationwide Cohort Study.

PURPOSE: In this study, we aimed to estimate recurrence risk after incident venous thromboembolism, stratified according to unprovoked, provoked, and cancer-related venous thromboembolism in a prospective cohort of inpatients and outpatients receiving routine care. METHODS: We linked nationwide Danish health registries to identify all patients with incident venous thromboembolism from January 2000 through December 2015. Rates of recurrence were calculated and Cox regression was used to compute hazard ratios (HRs) with 95% confidence intervals (CIs) by incident venous thromboembolism type after adjusting for coexisting risk factors. RESULTS: The study included 73,993 patients with incident venous thromboembolism (54.1% females; mean age, 62.3 years). At 6-month follow-up, rates per 100 person-years were 6.80, 6.92, and 9.06 for provoked, unprovoked, and cancer-related venous thromboembolism, respectively. At 10-year follow-up, corresponding rates were 2.22, 2.84, and 3.70, respectively. Additionally, at 6-month follow-up, hazard rates of recurrence were comparable for patients with unprovoked venous thromboembolism 1.01 (95% CI, 0.92-1.11) and provoked. At 10-year follow-up, unprovoked venous thromboembolism (HR, 1.17; 95% CI, 1.12-1.23) and cancer-related venous thromboembolism (HR, 1.21; 95% CI, 1.12-1.32) were associated with higher risk of recurrence compared with that found in provoked venous thromboembolism. CONCLUSIONS: In this nationwide cohort, patients with cancer-related venous thromboembolism had the highest risk of recurrence. At 6-month follow-up, there were similar risks of recurrence for patients with unprovoked and provoked venous thromboembolism. At 10-year follow-up, recurrence risks were similar for patients with unprovoked venous thromboembolism and patients with cancer-related venous thromboembolism. High recurrence risks in all categories indicate that further research is needed to optimize duration of extended anticoagulation for these patients.

Glomerular filtration rate in patients with atrial fibrillation and 1-year outcomes.

We assessed 1-year outcomes in patients with atrial fibrillation enrolled in the EurObservational Research Programme AF General Pilot Registry (EORP-AF), in relation to kidney function, as assessed by glomerular filtration rate (eGFR). In a cohort of 2398 patients (median age 69 years; 61% male), eGFR (ml/min/1.73 m(2)) calculated using the CKD-EPI formula was ≥80 in 35.1%, 50-79 in 47.2%, 30-49 in 13.9% and <30 in 3.7% of patients. In a logistic regression analysis, eGFR category was an independent predictor of stroke/TIA or death, with elevated odds ratios associated with severe to mild renal impairment, ie. eGFR < 30 ml/min/1.73 m(2) [OR 3.641, 95% CI 1.572-8.433, p < 0.0001], 30-49 ml/min/1.73 m(2) [OR 3.303, 95% CI 1.740-6.270, p = 0.0026] or 50-79 ml/min/1.73 m2 [OR 2.094, 95% CI 1.194-3.672, p = 0.0003]. The discriminant capability for the risk of death was tested among various eGFR calculation algorithms: the best was the Cockcroft-Gault equation adjusted for BSA, followed by Cockcroft-Gault equation, and CKD-EPI equation, while the worst was the MDRD equation. In conclusion in this prospective observational registry, renal function was a major determinant of adverse outcomes at 1 year, and even mild or moderate renal impairments were associated with an increased risk of stroke/TIA/death.

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study.

BACKGROUND: Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI). METHODS: Population-based cohort study of patients diagnosed with incident heart failure during 2000-2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease. RESULTS: 39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08-1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35-1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86-1.15 and 0.94, 95% CI: 0.89-1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes. CONCLUSIONS: Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.

Oral anticoagulants in coronary heart disease (Section IV). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.

Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.

Diabetes mellitus and risk of ischemic stroke in patients with heart failure and no atrial fibrillation.

OBJECTIVE: The risk of ischemic stroke, systemic thromboembolism, and all-cause death among heart failure patients previously diagnosed with diabetes mellitus is poorly described. We evaluated the risk of these endpoints among heart failure patients without diagnosed atrial fibrillation according to the presence of diabetes mellitus. METHODS: Population-based nationwide cohort study of non-anticoagulated patients diagnosed with incident heart failure during 2000-2012, identified by record linkage between nationwide registries in Denmark. We calculated relative risks after 1year to evaluate the association between diabetes and risk of events in 39,357 heart failure patients, among whom 18.1% had diabetes. Analysis took into account competing risks of death. RESULTS: Absolute risks of all endpoints were higher in patients with diabetes compared to patients without diabetes after 1-year follow-up (ischemic stroke: 4.1% vs. 2.8%; systemic thromboembolism: 11.9% vs. 8.6%; all-cause death: 22.1% vs. 21.4%). Diabetes was significantly associated with an increased risk of ischemic stroke (adjusted relative risk [RR]: 1.27, 95% confidence interval [CI]: 1.07-1.51); systemic thromboembolism (RR: 1.20, 95% CI: 1.11-1.30); and all-cause death (RR: 1.17, 95% CI: 1.11-1.23). Additionally, time since diabetes diagnosis was associated with higher adjusted cumulative incidences of ischemic stroke, systemic thromboembolism, and all-cause death (p for trend, p<0.001). CONCLUSIONS: Among heart failure patients without atrial fibrillation, diabetes was associated with a significantly increased risk of ischemic stroke, systemic thromboembolism, and all-cause death compared to those without diabetes, even after adjustment for concomitant cardiovascular risk factors. Increased focus on secondary prevention in heart failure patients with diabetes may be warranted.

'Real-world' management and outcomes of patients with paroxysmal vs. non-paroxysmal atrial fibrillation in Europe: the EURObservational Research Programme-Atrial Fibrillation (EORP-AF) General Pilot Registry.

AIMS: Atrial fibrillation (AF) has different presentations (first detected, paroxysmal, persistent, permanent), with uncertain impact on outcome. The aim of this study was to investigate clinical presentation, management, and outcome of paroxysmal and non-paroxysmal AFs within the EURObservational Research Programme-Atrial Fibrillation General Pilot Registry. METHODS AND RESULTS: Overall 2589 patients with available 1-year follow-up data were evaluated according to AF type. Patients with paroxysmal AF (26.8%) were younger, had lower prevalence of heart disease (particularly valvular), and major co-morbidities, as well as lower CHADS2, CHA2DS2-VASc, and HAS-BLED scores. Patients with first-detected AF (29.9%) had characteristics similar to persistent AF patients (25.9%), but lower use of oral anticoagulants. Patients with permanent AF represented 17.4% of the cohort. At 1 year, the rate of stroke/transient ischaemic attack and thromboembolism was low (0.6-1.0%) and did not differ between paroxysmal and non-paroxysmal AFs. All-cause mortality was higher in non-paroxysmal vs. paroxysmal AF (log rank test, P = 0.0018). Using a multivariable Cox model, non-paroxysmal AF was not an independent predictor of death during follow-up. Independent predictors of death were age, chronic heart failure, chronic kidney disease, diabetes, restrictive cardiomyopathy, and physical activity. CONCLUSION: In this 'real-world' contemporary observational registry, patients with non-paroxysmal AF had a worse outcome, in terms of all-cause mortality, which was related to a more severe clinical profile. The risk of stroke at 1 year was relatively low, perhaps reflecting the high rates of anticoagulation use in this cohort.

Improved outcomes with European Society of Cardiology guideline-adherent antithrombotic treatment in high-risk patients with atrial fibrillation: a report from the EORP-AF General Pilot Registry.

AIMS: Guideline-adherent therapy for stroke prevention in atrial fibrillation has been associated with better outcomes, in terms of thromboembolism (TE) and bleeding. METHODS AND RESULTS: In this report from the EuroObservational Research Programme-Atrial Fibrillation (EORP-AF) Pilot General Registry, we describe the associated baseline features of 'high risk' AF patients in relation to guideline-adherent antithrombotic treatment, i.e. whether they were adherent, over-treated, or under-treated based on the 2012 European Society of Cardiology (ESC) guidelines. Secondly, we assessed the predictors of guideline-adherent antithrombotic treatment. Thirdly, we evaluated outcomes for all-cause mortality, TE, bleeding, and the composite endpoint of 'any TE, cardiovascular death or bleeding' in relation to whether they were ESC guideline-adherent treatment. From the EORP-AF cohort, the follow-up dataset of 2634 subjects was used to assess the impact of guideline adherence or non-adherence. Of these, 1602 (60.6%) were guideline adherent, whilst 458 (17.3%) were under-treated, and 574 (21.7%) were over-treated. Non-guideline-adherent treatment can be related to region of Europe as well as associated clinical features, but not age, AF type, symptoms, or echocardiography indices. Over-treatment per se was associated with symptoms, using the EHRA score, as well as other comorbidities. Guideline-adherent antithrombotic management based on the ESC guidelines is associated with significantly better outcomes. Specifically, the endpoint of 'all cause death and any TE' is increased by >60% by undertreatment [hazard ratio (HR) 1.679 (95% confidence interval (CI) 1.202-2.347)] or over-treatment [HR 1.622 (95% CI 1.173-2.23)]. For the composite endpoint of 'cardiovascular death, any TE or bleeding', over-treatment increased risk by >70% [HR 1.722 (95% CI 1.200-2.470)]. CONCLUSION: Even in this cohort with high overall rates of oral anticoagulation use, ESC guideline-adherent antithrombotic management is associated with significantly better outcomes, including those related to mortality and TE, as well as the composite endpoint of 'cardiovascular death, any TE or bleeding'. These contemporary observations emphasize the importance of guideline implementation, and adherence to the 2012 ESC guidelines for stroke prevention in AF.

Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation.

IMPORTANCE: The CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) is used clinically for stroke risk stratification in atrial fibrillation (AF). Its usefulness in a population of patients with heart failure (HF) is unclear. OBJECTIVE: To investigate whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in a cohort of patients with HF with and without AF. DESIGN, SETTING, AND POPULATION: Nationwide prospective cohort study using Danish registries, including 42 987 patients (21.9% with concomitant AF) not receiving anticoagulation who were diagnosed as having incident HF during 2000-2012. End of follow-up was December 31, 2012. EXPOSURES: Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk), stratified by concomitant AF at baseline. Analyses took into account the competing risk of death. MAIN OUTCOMES AND MEASURES: Ischemic stroke, thromboembolism, and death within 1 year after HF diagnosis. RESULTS: In patients without AF, the risks of ischemic stroke, thromboembolism, and death were 3.1% (n = 977), 9.9% (n = 3187), and 21.8% (n = 6956), respectively; risks were greater with increasing CHA2DS2-VASc scores as follows, for scores of 1 through 6, respectively: (1) ischemic stroke with concomitant AF: 4.5%, 3.7%, 3.2%, 4.3%, 5.6%, and 8.4%; without concomitant AF: 1.5%, 1.5%, 2.0%, 3.0%, 3.7%, and 7% and (2) all-cause death with concomitant AF: 19.8%, 19.5%, 26.1%, 35.1%, 37.7%, and 45.5%; without concomitant AF: 7.6%, 8.3%, 17.8%, 25.6%, 27.9%, and 35.0%. At high CHA2DS2-VASc scores (≥4), the absolute risk of thromboembolism was high regardless of presence of AF (for a score of 4, 9.7% vs 8.2% for patients without and with concomitant AF, respectively; overall P<.001 for interaction). C statistics and negative predictive values indicate that the CHA2DS2-VASc score performed modestly in this HF population with and without AF (for ischemic stroke, 1-year C statistics, 0.67 [95% CI, 0.65-0.68] and 0.64 [95% CI, 0.61-0.67], respectively; 1-year negative predictive values, 92% [95% CI, 91%-93%] and 91% [95% CI, 88%-95%], respectively). CONCLUSIONS AND RELEVANCE: Among patients with incident HF with or without AF, the CHA2DS2-VASc score was associated with risk of ischemic stroke, thromboembolism, and death. The absolute risk of thromboembolic complications was higher among patients without AF compared with patients with concomitant AF at high CHA2DS2-VASc scores. However, predictive accuracy was modest, and the clinical utility of the CHA2DS2-VASc score in patients with HF remains to be determined.

Pre-existing atrial fibrillation and risk of arterial thromboembolism and death in intensive care unit patients: a population-based cohort study.

INTRODUCTION: Pre-existing atrial fibrillation (AF) may worsen prognosis in patients admitted to the intensive care unit (ICU). METHODS: In a cohort study (2005-2011) including all patients with first-time ICU admissions in Denmark (n=57,110), we compared patients with and without pre-existing AF and estimated absolute risks and relative risks (RRs) of arterial thromboembolism and death within 30 days and 365 days following admission, using Kaplan-Meier methods and multivariate regression analyses. We analysed the prognostic impact of AF within strata of patient age, sex, coexisting cardiac diseases, and ICU therapies. RESULTS: Among ICU patients, 5065 (9%) had pre-existing AF. Compared with patients without AF, those with AF were older (median age 75 vs. 62 years) and had more comorbidity. The risk of arterial thromboembolism was 2.8% in patients with AF and 2.0% in non-AF patients at 30 days, and 4.3% and 2.9%, respectively, at 365 days. Corresponding RRs were 1.41 crude and 1.14 (95% confidence interval [CI] 0.93-1.40) adjusted at 30 days, and 1.50 crude and 1.20 (95% CI 1.02-1.41) adjusted at 365 days. Thirty-day mortality was 27% in patients with pre-existing AF and 16% in non-AF patients (crude RR 1.67, adjusted RR 1.04, 95% CI 0.99-1.10). Corresponding mortality estimates at 365 days were 40.9% and 25.4%, respectively (crude RR 1.61, adjusted RR 1.03, 95% CI 1.00-1.07). In stratified analyses, pre-existing AF increased mortality in ICU patients aged <55 years (adjusted RR at 30 days 1.73, 95% CI 1.29-2.32; adjusted RR at 365 days 1.34, 95% CI 1.06-1.69) and in ICU patients treated with mechanical ventilation (adjusted RR at 30 days 1.12, 95% CI 1.05-1.20, adjusted RR at 365 days 1.09, 95% CI: 1.04-1.15). Analyses stratified by sex and coexisting cardiac diseases yielded adjusted RRs close to 1. CONCLUSIONS: In ICU patients, pre-existing AF was associated with modestly increased risk of arterial thromboembolism when adjusted for the substantially higher age and comorbidity levels in patients with AF, whereas there was no overall association with mortality. In ICU patients aged <55 years and in those treated with mechanical ventilation, AF predicted increased mortality.

Duration of Diabetes Mellitus and Risk of Thromboembolism and Bleeding in Atrial Fibrillation: Nationwide Cohort Study.

BACKGROUND AND PURPOSE: 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 CHA2DS2-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.

Atrial flutter and thromboembolic risk: a systematic review.

Atrial flutter confers a thromboembolic risk, but contrary to atrial fibrillation the relationship has only been addressed in few studies. This study performs an up to date systematic review of the literature to investigate the association between atrial flutter and thromboembolic events. Articles were found by MEDLINE, EMBASE search and a manual search of references list in included articles. International guidelines, meta-analyses, reviews, case reports, studies reporting thromboembolic events in relation to ablation, or cardioversion procedures, echocardiography, and observational studies were found eligible in this review. A total of 52 articles were included in this review. During cardioversion, thromboembolic event rates varied from 0% to 6% with a follow-up from 1 week to 6 years. Echocardiographic studies reported prevalence of thrombus material from 0% to 38% and a prevalence of spontaneous echo contrast (SEC) from 21% to 28%. One ablation study in non-anticoagulated patients reported thromboembolic events at 13.9%. Observational studies reported an overall elevated stroke risk (risk ratio 1.4, 95% CI 1.35 to 1.46) and mortality risk (HR 1.9, 95% CI 1.2 to 3.1) with long time follow-up compared with a control group in both studies. Given the limitations and heterogeneity of the data, a meta-analysis was not a part of this systematic review. Notwithstanding the limitations of observational studies and indirect data from echocardiographic studies, this systematic review confirms that clinical thromboembolic events, left atrial thrombus and SEC are highly prevalent in atrial flutter.

Blood pressure and prognosis in patients with incident heart failure: the Diet, Cancer and Health (DCH) cohort study.

BACKGROUND: Our objective was to test the hypothesis that elevated blood pressure (BP) is associated with increased risk of stroke, bleeding and death in patients with incident heart failure (HF). METHODS: We conducted a prospective cohort study among subjects who were participants in the Diet, Cancer and Health study, born in Denmark, aged 50-64 years at recruitment. We assessed stroke (ischemic stroke or systemic embolic events), major bleeding, death and the composite endpoint according to degree of BP control in patients with incident HF. BP was assessed prior to HF at cohort entry. RESULTS: Of the whole cohort of 55,748 subjects, n = 2159 (35 % female) had incident HF, of which 12 % had treatment for hypertension. Median follow-up after incident HF was 3.5 years. High systolic (SBP), diastolic (DBP) and pulse (PP) pressures were associated with an increased risk of stroke, major bleeding and the composite endpoint. For death and stroke/death, the relation appeared U-shaped for SBP and DBP. When comparing the highest quartile group (Q4) to first quartile group (Q1), SBP (Q4: SBP >163 mmHg) was associated with significantly higher adjusted hazard rate ratio (HR) for stroke (HR 1.46, 95 % CI 1.00-2.14) and major bleeding (HR 1.68, 95 % CI 1.12-2.53). For DBP (Q4: DBP >94 mmHg), adjusted HR was significantly higher for major bleeding (HR 1.63, 95 % CI 1.13-2.38). The highest quartile of pulse pressure (Q4: PP >74 mmHg) was associated with non-significantly higher risk of stroke (HR 1.40, 95 % CI 0.94-2.06). CONCLUSION: We have shown for the first time that amongst a population with incident HF, higher baseline systolic, diastolic and pulse pressure levels were associated with a higher rate of adverse events. Our data support the importance for optimised BP control, as part of the holistic management of HF patients.

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

BACKGROUND: Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. METHODS AND RESULTS: Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. CONCLUSIONS: Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality rates, supporting oral anticoagulant treatment reintroduction after intracranial hemorrhage as feasible. Future trials are encouraged to guide clinical practice in these patients.

Female sex is associated with a lower risk of stroke in patients with heart failure.

BACKGROUND: Stroke in patients with heart failure is associated with poor outcomes. Risk stratification schemes may improve clinical decision making in this patient population. This study investigated whether female sex is a risk factor for stroke in patients with heart failure in sinus rhythm. METHODS: This is a population-based cohort study of patients diagnosed with heart failure during 2000 to 2012, identified by record linkage between nationwide Danish registries. Our primary outcome was stroke, and secondary outcome was thromboembolic event. We used relative risks (RRs) after 1 and 5 years to compare males with females within each of the following age groups: 50 to 59 years, 60 to 69 years, 70 to 79 years, 80 to 89 years, and 90+ years. Analyses took into account the competing risks of death. RESULTS: During the study period, 84,142 patients were diagnosed with heart failure, of which 39,946 (47.5%) were females. At 5-year follow-up, female sex was associated with a lower risk of stroke compared with males (adjusted overall hazard ratio 0.91, 95% CI 0.85-0.96). The observed lower risks of stroke in females were not present in the older age groups, where the competing risk of death was substantial among males in particular. When considering a more broadly defined thromboembolic end point, a decreased risk among females persisted across nearly all age groups after 5-year follow-up (adjusted overall hazard ratio 0.93, 95% CI 0.91-0.96). CONCLUSIONS: We found an association between female sex and decreased stroke risk in patients with heart failure, which persisted after adjustment for concomitant cardiovascular risk factors. The association was attenuated with increasing age, possibly because of competing risks of death.

Oral anticoagulation, aspirin, or no therapy in patients with nonvalvular AF with 0 or 1 stroke risk factor based on the CHA2DS2-VASc score.

BACKGROUND: Even a single additional stroke risk factor in patients with atrial fibrillation may confer a risk of stroke. However, there is no consensus on how best to treat these patients. OBJECTIVES: Our objective was to investigate the risk of stroke and bleeding and the impact of antithrombotic therapy among low-risk patients, i.e., with 0 or 1 CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score risk factor. METHODS: The nationwide cohort for this study was established by linking data from the Danish Civil Registration System, the Danish National Patient Register, and the Danish National Prescription Registry. We studied 39,400 patients discharged with incident nonvalvular atrial fibrillation with 0 or 1 CHA2DS2-VASc risk factor; 23,572 were not treated, 5,353 were initiated on aspirin, and 10,475 were initiated on warfarin. RESULTS: Stroke event rates for untreated low-risk patients (CHA2DS2-VASc = 0 [male], 1 [female]) were 0.49 per 100 person-years at 1 year and 0.47 per 100 person-years at full follow-up (intention-to-treat). Bleeding event rates among untreated low-risk patients were 1.08 per 100 person-years at 1 year and 0.97 at full follow-up. The presence of 1 additional stroke risk factor (CHA2DS2-VASc = 1 [male], = 2 [female]) among untreated patients increased the stroke rate at 1 year to 1.55 per 100 person-years, representing a significant 3.01-fold increase. At the 1-year follow-up, bleeding increased 2.35-fold, and death increased 3.12-fold. CONCLUSIONS: Low-risk patients (CHA2DS2-VASc = 0 [male], 1 [female]) have a truly low risk for stroke and bleeding. With 1 additional stroke risk factor (CHA2DS2-VASc = 1 [male], = 2 [female]), there was a significant increase in event rates (particularly mortality) if nonanticoagulated.

Use of psychotropic drugs following venous thromboembolism in youth. A nationwide cohort study.

INTRODUCTION: The mental health prognosis following a venous thromboembolism in youth has not been investigated comprehensively. Using psychotropic drug purchase as a proxy for mental health status, we investigated this issue in a large cohort of young incident venous thromboembolism patients. METHODS: Using Danish nationwide administrative registries from the period 1997-2010, we identified 4,132 patients aged 13-33 years with a first-time venous thromboembolism diagnosis and no history of psychotropic drug usage. We sampled comparison cohort of random general population controls, matched individually in a 1:5 ratio based on sex and birth year. Participants were followed in prescription purchase registries for their first psychotropic drug purchase. RESULTS: Among young venous thromboembolism case cases, the 1-year risk of psychotropic drug purchase was 7.1% (95% confidence interval [CI] 6.3, 7.9) and the 5-year risk 22.1% (95% CI 20.7, 23.5). This was substantially higher than among population controls, with 1- and 5-year risk differences relative to the controls of 4.7% (95% CI 3.9, 5.5), and 10.8% (95% CI 9.4, 12.3), respectively. Adjustment for the effects of recent pregnancy or somatic provocations attenuated risk differences to 4.1% (95% CI 3.5, 5.1) after 1 year and 9.6% (95% CI 8.3, 11.2) after 5 years. CONCLUSIONS: A venous thromboembolism diagnosis in youth is associated with a poorer mental health prognosis: one in five patients are prescribed psychotropic medication within the first 5 year after diagnosis.