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Aims: To describe the risks of thromboembolism and major bleeding complications in anticoagulated patients with atrial fibrillation (AF) and native aortic or mitral valvular heart disease using data reflecting clinical practice., Methods and Results: Descriptive cohort study of anticoagulated patients with incident AF and native aortic or mitral valvular heart disease, identified in nationwide Danish registries from 2000 to 2018. A total of 10 043 patients were included, of which 5190 (51.7%) patients had aortic stenosis, 1788 (17.8%) patients had aortic regurgitation, 327 (3.3%) patients had mitral stenosis, and 2738 (27.3%) patients had mitral regurgitation. At 1 year after AF diagnosis, the risk of thromboembolism was 4.6% in patients with mitral stenosis taking a vitamin K antagonist (VKA), and 2.6% in patients with aortic stenosis taking a VKA or non-vitamin K antagonist oral anticoagulant (NOAC). For patients with aortic or mitral regurgitation, the risks of thromboembolism ranged between 1.5%-1.8% in both treatment groups. For the endpoint of major bleeding, the risk was ∼5.5% in patients with aortic stenosis or mitral stenosis treated with a VKA, and 3.3-4.0% in patients with aortic or mitral regurgitation. For patients treated with a NOAC, the risk of major bleeding was 3.7% in patients with aortic stenosis and ∼2.5% in patients with aortic or mitral regurgitation., Conclusion: When using data reflecting contemporary clinical practice, our observations suggested that 1 year after a diagnosis of AF, anticoagulated patients with aortic or mitral valvular heart disease had dissimilar risk of thromboembolism and major bleeding complications. Specifically, patients with aortic stenosis or mitral stenosis were high-risk subgroups. This observation may guide clinicians regarding intensity of clinical follow-up., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study sought to describe the risk of thromboembolism in nonanticoagulated atrial fibrillation patients with Evaluated Heartvalves, Rheumatic or Artificial (EHRA) Type 2 valvular heart disease (VHD) <65 or 65 to 74 years of age and with 0 or 1 non-sex comorbidity of the CHA 2 DS 2 -VASc score., Background: A minor, but important, proportion of patients with atrial fibrillation and VHD beyond moderate-to-severe mitral stenosis and/or a mechanical prosthetic valve, so-called EHRA Type 2 VHD, have 0 or 1 coexisting non-sex comorbidities of the CHA 2 DS 2 -VASc score, and are therefore not strongly recommended oral anticoagulant therapy according to guidelines. Whether these patients are truly low risk of thromboembolism has not been investigated., Methods: This was a cohort study of 55,613 patients identified in nationwide Danish registries from 2000 to 2018, of which 1,907 patients had EHRA Type 2 VHD. Risk of thromboembolism after 1 and 5 years of follow-up were calculated., Results: At 1 year after atrial fibrillation diagnosis, patients with EHRA Type 2 VHD had a risk of thromboembolism between 1.2% and 1.5%, according to age group (<65 or 65 to 74 years of age), and number of non-sex comorbidities of the CHA 2 DS 2 -VASc score (0 or 1). Interestingly, in patients with EHRA Type 2 VHD <65 years of age with 0 or 1 comorbidity, the risk was 1.5% (95% confidence interval: 0.7% to 2.8%) and 1.5% (95% confidence interval: 0.6% to 3.4%) at 1 year after the atrial fibrillation diagnosis., Conclusions: These observations suggest that in atrial fibrillation patients with EHRA Type 2 VHD, who are not currently recommended oral anticoagulant therapy according to guidelines, the risk of thromboembolism may exceed the level above which oral anticoagulation is considered beneficial., Competing Interests: Author Disclosures The study was supported by “The BMS/Pfizer European Thrombosis Investigator Initiated Research Program (ERISTA) 2018” and the Obel Family Foundation. Dr. Melgaard has received grant support from Bristol-Myers Squibb/Pfizer. Prof. Lip has been a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife, and Daiichi Sankyo; and has been a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche, and Daiichi Sankyo. No fees were received personally. Prof. Larsen has been an investigator for Janssen Scientific Affairs, LLC, and Boehringer Ingelheim; and has been a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Janssen Pharmaceuticals, Takeda, Roche Diagnostics, and Boehringer Ingelheim. No fees were received personally. Dr. Nielsen has received speaking fees from Boehringer Ingelheim; has received consulting fees from Bayer; and has received grant support from Bristol-Myers Squibb/Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Diabetes mellitus is associated with increased risk of stroke in patients with atrial fibrillation, and differences in glycemic status may affect this risk. We aimed to examine the effect of glycemic status evaluated by hemoglobin A1c (HbA1c) on the risk of thromboembolism among patients with atrial fibrillation and type 2 diabetes mellitus. Methods In this cohort study, we used data from Danish registries to identify patients with type 2 diabetes mellitus and incident nonvalvular atrial fibrillation in the period of May 1, 2005, through December 31, 2015. On the basis of the most recent HbA1c measurement before an incident atrial fibrillation diagnosis, patients were divided into the categories: HbA1c ≤48 mmol/mol, HbA1c=49-58 mmol/mol, and HbA1c >58 mmol/mol. Cox regression analysis was used to estimate hazard ratios for the outcome thromboembolism. Results The study population included 5386 patients with incident nonvalvular atrial fibrillation and type 2 diabetes mellitus. Compared with patients with HbA1c ≤48 mmol/mol, we observed a higher risk of thromboembolism among patients with HbA1c=49-58 mmol/mol (hazard ratio, 1.49; 95% CI, 1.09-2.05) and HbA1c >58 mmol/mol (hazard ratio, 1.59; 95% CI, 1.13-2.22) after adjusting for confounding factors. When stratified on diabetes mellitus duration, similar results were found among patients with diabetes mellitus duration of <10 years. Contrastingly, in patients with diabetes mellitus duration of ≥10 years, higher HbA1c levels were not associated with a higher risk of thromboembolism. Conclusions In patients with incident atrial fibrillation and type 2 diabetes mellitus, increasing levels of HbA1c were associated with a higher risk of thromboembolism. However, no association was found among patients with diabetes mellitus duration ≥10 years.

Contemporary guidelines suggest anticoagulant treatment decisions in atrial fibrillation (AF) patients to be based on risk stratification for stroke. However, guidelines do not agree on the threshold for treatment initiation. We explored the variation in thromboembolic event rates in a non-anticoagulated AF population, according to different guideline threshold and methodological approaches. AF patients between 1998 and 2014 free from anticoagulant treatment were identified. Event rates for ischemic stroke and ischemic stroke/systemic embolism were explored. The overall ischemic stroke rate was 3.20 per 100 person-years ('formal rate assessment'). For patients with a CHA2DS2-VASc score of 1 the ischemic stroke rate was 0.97 when using a 'formal rate assessment', 0.62 when using a 'conditioning on the future' approach, and 0.93 when using a 'censoring approach'. Rates for thromboembolism for the 'European treatment threshold' (CHA2DS2-VASc score of 1, males only) ranged 1.17 to 1.53. Rates for the 'U.S. treatment threshold' (CHA2DS2-VASc of 2) ranged from 1.95 to 2.33. Thromboembolic event rates differed markedly in non-anticoagulated AF patients according to the conflicting European and U.S. guideline treatment thresholds. Second, the choice of methodological approach has implications, thus we recommend using the censoring approach for event rate estimation among AF patients not on treatment.

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., (© 2015 American Heart Association, Inc.)

Several studies have demonstrated sex differences in risk of thromboembolism and death among patients with atrial fibrillation, but it is unclear to what extent these associations relate to actual physiological differences. To date, no study has investigated sex differences with concomitant control for lifestyle related factors known to influence stroke risk. We used data from the Danish Diet, Cancer and Health study, including 57,053 participants (52% female) aged 50-64 years. The study population for this study included the 2,895 patients (36% female) with incident atrial fibrillation after inclusion. Data were linked to outcomes identified using nationwide registries. Risk of thromboembolism and death according to female sex were analysed using Cox proportional hazards models. After a median follow-up of 5.0 years, 137 men and 62 women suffered a thromboembolic event, and 349 men and 151 women died. In a crude analysis, female sex was associated with a non-significant lower risk of thromboembolism (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.61-1.11). Adjustment for differences in antithrombotic therapy, relevant comorbidities and lifestyle did not change this association (HR 0.77, 95% CI 0.55-1.13). In the final model, female sex was associated with a lower risk of death (HR 0.65, 95% CI 0.51-0.84). The associations were similar in a sensitivity analysis of women not taking hormone replacement therapy, and the effect of hormone replacement therapy use within females was non-significant for both endpoints of thromboembolism and death. In conclusion, in a relatively young population of patients with atrial fibrillation, female sex was associated with a lower risk of thromboembolism and death.

Background: Smoking and atrial fibrillation (AF) are major health problems worldwide and are responsible for substantial health-care costs. Our aim was to investigate whether smoking impacts the risk of stroke and death in patients with AF. To test this hypothesis, we analyzed data from a large Danish cohort: the Diet, Cancer, and Health study., Methods: This was a cohort study of 57,053 people (27,178 men; 29,876 women) aged 50 to 64 years. The risk of thromboembolism (ischemic stroke/arterial thromboembolism) or death according to smoking habits among 3,161 patients with incident AF (mean age, 66.9 years; 2,032 men, 1,129 women) was assessed using Cox proportional hazard models after a median follow-up of 4.9 years., Results: Of those with AF, 34% were current smokers and 37% former smokers. After adjustment for vitamin K antagonist treatment, the hazard ratios (HRs) (95% CI) of thromboembolism or death were 3.13 (1.72-6.37) and 2.73 (2.02-3.70) among women and men who currently were heavy smokers (>25 g/d), respectively. The associations remained after adjustment for well-established risk factors with HRs of 3.64 (1.88-7.07) and 2.17 (1.59-2.95) among women and men, respectively. In a sensitivity analysis, smoking was still strongly associated with thromboembolism or death after censoring people with a cancer diagnosis during follow-up., Conclusions: Smoking is associated with a higher risk of thromboembolism or death in patients with AF even after adjusting for well-recognized risk factors used in stroke risk stratification schemes. The associations may be modified by sex, as the associations were strongest among women.

Objective: To assess alcohol intake as a risk factor for adverse events among patients with incident atrial fibrillation (AF)., Design: Prospective cohort study., Setting: Population based cohort study and nationwide Danish registries., Patients: The Danish Diet, Cancer and Health study included 57 053 participants (27 178 men and 29 875 women) aged between 50 and 64 years. The study population for this study included the 3107 participants (1999 men, 1108 women) who developed incident AF after inclusion., Main Outcome Measures: A composite of thromboembolism or death., Results: During a median follow-up of 4.9 years 608 deaths and 211 thromboembolic events occurred. Of those who developed AF, 690 (35%) men and 233 (21%) women had a high intake of alcohol (>20 drinks/week for men and >13 drinks/week for women). After adjustment for use of oral anticoagulation and components of the CHA2DS2-VASc score, men with an intake of >27 drinks/week had a higher risk for thromboembolism or death (hazard ratio (HR) 1.33, 95% CI 1.08 to 1.63) than men with an intake of <14 drinks/week. Women with an intake of >20 drinks/week also had a higher risk (HR 1.23, 95% CI 0.78 to 1.96) than women in the low intake category. The higher risk among men was primarily driven by mortality (HR 1.51, 95% CI 1.20 to 1.89), whereas the risk found among women was driven by thromboembolism (HR 1.71, 95% CI 0.81 to 3.60)., Conclusions: High alcohol intake predicts thromboembolism or death, even after adjustment for established clinical risk factors, and may help identify high risk AF patients who could be targeted for stroke and cardiovascular prevention strategies.

Background: Obesity is associated with the development of atrial fibrillation and may impact atrial fibrillation-related outcomes. To date, no anthropometric measure is included in any risk stratification scheme for stroke and death in atrial fibrillation patients., Methods: The prospective Danish Diet, Cancer and Health study is a cohort including 57,053 participants (27,178 men and 29,875 women) aged between 50 and 64 years. The study population for this study included the 3135 patients (2025 men and 1110 women) who developed incident atrial fibrillation during follow-up., Results: Of the subjects with atrial fibrillation, 1414 (45%) had a body mass index (BMI) in the overweight category (BMI 25 to <30 kg/m(2)) and 767 (24%) were categorized as obese (BMI ≥30 kg/m(2)). During a median follow-up of 4.9 years, 609 deaths and 216 thromboembolic events (98% ischemic strokes) occurred. Using normal-weight patients as reference, the risk of a composite end point of "ischemic stroke, thromboembolism, or death" was significantly higher in overweight (crude hazard ratio [HR] 1.31; 95% confidence interval [CI], 1.09-1.56) and obese patients (crude HR 1.55; 95% CI 1.27-1.90). After adjustment for CHADS2 and CHA2DS2-VASc scores, the HRs for the composite end point were 1.21 (95% CI 1.02-1.45) and 1.31 (95% CI 1.10-1.56), respectively, for overweight and 1.25 (95% CI 1.03-1.53) and 1.36 (95% CI 1.11-1.65), respectively, for obese. Continuous analyses of BMI stratified by sex identified obese men and normal-weight women as the sex-specific "high-risk" categories., Conclusion: Overweight and obesity are risk factors for "ischemic stroke, thromboembolism or death" in patients with atrial fibrillation, even after adjustment for CHADS2 and CHA2DS2-VASc scores. The association between BMI and outcomes among atrial fibrillation patients may be modified by sex., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Hospital discharge diagnoses from administrative registries are frequently used in studies of cancer-associated venous thromboembolism, but the validity of International Classification of Diseases (ICD) codes for identifying such events is unknown. Using patient samples from the Danish National Patient Register, we calculated positive predictive values (PPV), i.e., the proportion of registered ICD codes, which could be confirmed after manual search of the electronic health record. Sensitivity was estimated in a sample of patients with imaging-verified venous thromboembolism but without prior knowledge about their ICD coding status. Sensitivity was calculated as the proportion of these patients, who were discharged with an ICD code for venous thromboembolism. The overall PPV of an ICD-10 diagnosis of cancer-associated venous thromboembolism was 75.9 % (95 % confidence interval 71.3–80.0). In subgroups, the PPV was particularly low for recurrent venous thromboembolism (44.2 %), diagnoses in a secondary position (55.7 %), outpatient diagnoses (65.3 %), and diagnoses given at surgical (66.7 %), emergency wards (48.4 %), or via hospices/palliative teams (0 %). The overall sensitivity was 68 %, meaning 32 % of patients with cancer diagnosed in hospital with venous thromboembolism were discharged without any registered ICD code for venous thromboembolism. The positive predictive value of an ICD diagnosis of cancer-associated venous thromboembolism in the Danish Patient Register was overall adequate for research purposes, but with notable variation across subgroups. Sensitivity was limited, as 1/3 of patients with venous thromboembolism were discharged without any relevant ICD code. Cautious interpretation of incidence of cancer-associated venous thromboembolism based on administrative register-based data is warranted. • Venous thromboembolism is common among patients with cancer. • The quality of ICD-10 diagnoses for identifying such events is unknown. • The positive predictive value in the Danish National Patient Register was 75.9 %. • Sensitivity was limited, with 1/3 patients discharged without a relevant ICD code. • Administrative discharge diagnoses for cancer-associated thromboembolism venous should be used with caution. [ABSTRACT FROM AUTHOR]

Cancer-associated venous thromboembolism remains an important but challenging aspect in the treatment of patients with cancer. Recently, alternatives to injection of low-molecular-weight heparin (LMWH) have been introduced, the non-vitamin K antagonist oral anticoagulants (NOACs), which could potentially alleviate patients from burdensome daily injections. This review discusses the available evidence exploring the role of NOACs in the treatment and secondary prevention of cancer-associated venous thromboembolism, from randomized trials, observational data, contemporary guideline recommendations, and patient perspectives. Edoxaban, rivaroxaban, and apixaban have proven attractive alternatives to LMWH for the treatment of cancer-associated venous thromboembolism. Contemporary guidelines have promptly endorsed the use of NOACs in patients with most cancer types. Nonetheless, issues remain regarding bleeding risk, interactions with medical cancer treatment, and the effectiveness and safety for extended treatment periods. There are head-to-head comparisons of the NOACs, and therefore no data favoring the use of one NOAC over the others. Patient's preferences are highly diverse and should be part of routine considerations when weighing risks and benefits associated with various available anticoagulant drugs. [ABSTRACT FROM AUTHOR]

Background: Smoking and atrial fibrillation (AF) are major health problems worldwide and are responsible for substantial health-care costs. Our aim was to investigate whether smoking impacts the risk of stroke and death in patients with AF. To test this hypothesis, we analyzed data from a large Danish cohort: the Diet, Cancer, and Health study.Methods: This was a cohort study of 57,053 people (27,178 men; 29,876 women) aged 50 to 64 years. The risk of thromboembolism (ischemic stroke/arterial thromboembolism) or death according to smoking habits among 3,161 patients with incident AF (mean age, 66.9 years; 2,032 men, 1,129 women) was assessed using Cox proportional hazard models after a median follow-up of 4.9 years.Results: Of those with AF, 34% were current smokers and 37% former smokers. After adjustment for vitamin K antagonist treatment, the hazard ratios (HRs) (95% CI) of thromboembolism or death were 3.13 (1.72-6.37) and 2.73 (2.02-3.70) among women and men who currently were heavy smokers (> 25 g/d), respectively. The associations remained after adjustment for well-established risk factors with HRs of 3.64 (1.88-7.07) and 2.17 (1.59-2.95) among women and men, respectively. In a sensitivity analysis, smoking was still strongly associated with thromboembolism or death after censoring people with a cancer diagnosis during follow-up.Conclusions: Smoking is associated with a higher risk of thromboembolism or death in patients with AF even after adjusting for well-recognized risk factors used in stroke risk stratification schemes. The associations may be modified by sex, as the associations were strongest among women. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate whether history of venous thromboembolism should be considered a prognostic factor for future thromboembolic events in patients with atrial fibrillation.Methods: This was a nationwide cohort study of patients with incident atrial fibrillation from 2000-2017, defined and characterized using Danish health registries. Cox regression analyses were used to calculate hazard ratios and 95% confidence intervals for the outcomes ischemic stroke or systemic embolism, and ischemic stroke, systemic embolism, or venous thromboembolism, according to history of venous thromboembolism. Analyses were adjusted for components of the CHA2DS2-VASc score and time-varying use of oral anticoagulation.Results: The study included 246,313 patients with incident atrial fibrillation, of which 6,516 (2.6%) had previous venous thromboembolism. Patients with previous venous thromboembolism carried an overall similar adjusted risk of ischemic stroke or systemic embolism compared with patients without previous venous thromboembolism (reference; hazard ratio 0.99; 95% confidence interval, 0.90-1.09). When analyzing a composite thromboembolic outcome of ischemic stroke, systemic embolism, or venous thromboembolism, patients with previous venous thromboembolism were at high-risk (hazard ratio 1.76; 95% confidence interval, 1.64-1.90). Similar conclusions were drawn when stratifying by venous thromboembolism subtype, and when restricting to patients with low CHA2DS2-VASc scores or the non-anticoagulated subset of the study population.Conclusion: Patients with atrial fibrillation and previous venous thromboembolism carried similar risk of ischemic stroke or systemic embolism compared with patients with atrial fibrillation without previous venous thromboembolism. Nonetheless, patients with previous venous thromboembolism remain a high-risk population due to an excess risk of future venous thromboembolism. Patients and physicians should keep this excess thromboembolic risk in mind when weighing the expected risks and benefits of oral anticoagulation in patients with atrial fibrillation. [ABSTRACT FROM AUTHOR]

Background: Stroke risk in atrial fibrillation is assessed by using the CHA2DS2-VASc score. Sex category (Sc, ie, female sex) confers 1 point on CHA2DS2-VASc. We hypothesized that female sex is a stroke risk modifier, rather than an overall risk factor, when added to a CHA2DS2-VA (sex-independent thromboembolism risk) score scale.Methods: Using 3 nationwide registries, we identified patients with incident nonvalvular atrial fibrillation from January 1, 1997, through December 31, 2015. Patients receiving oral anticoagulant treatment at baseline were excluded, and person-time was censored at the time of treatment initiation (if any). CHA2DS2-VA scores were calculated for men and women, and were followed for up to 1 year in the Danish National Patient Registry. The primary outcome was a primary hospital code for ischemic stroke or systemic embolism (thromboembolism). We calculated crude event rates for risk strata as events per 100 person-years. For quantifying absolute risk of stroke, we calculated risks based on the pseudovalue method. Female sex as a prognostic factor was investigated by inclusion as an interaction term on the CHA2DS2-VA score to calculate the thromboembolic risk ratio for different score points.Results: A total of 239 671 patients with atrial fibrillation (48.7% women) contributed to the analyses. The mean ages for women and men were 76.6 years and 70.3 years, respectively; the mean CHA2DS2-VA scores were 2.7 for women and 2.3 for men. The overall 1-year thromboembolic rate per 100 person-years for women was 7.3 and 5.7 for men. The 1-year absolute risk of thromboembolism was 0.5% among men and women with a CHA2DS2-VA score of 0 and increased up to >7% among very comorbid patients (score >5). The risk ratio (male as reference) across points >1 indicated that women exhibit a higher stroke risk. The interaction was statistically significant (P<0.001).Conclusions: Female sex is a risk modifier for stroke in patients with atrial fibrillation. Initial decisions on oral anticoagulant treatment could be guided by a CHA2DS2-VA score (ie, excluding the sex category criterion), but the Sc risk component modifies and accentuates stroke risk in women who would have been eligible for oral anticoagulant treatment on the basis of ≥2 additional stroke risk factors. [ABSTRACT FROM AUTHOR]

Predictive factors for recurrent cancer-associated venous thromboembolism have been inconsistent across previous studies. To provide data for improved risk stratification, we described the risk of recurrent venous thromboembolism overall and across age, sex, calendar period, cancer type, Ottawa risk score, cancer stage, and cancer treatment in a nationwide cohort of patients with active cancer. Using Danish administrative registries, we identified a cohort of all adult patients with active cancer and a first-time diagnosis of venous thromboembolism during 2003–2018. We accounted for the competing risk of death and calculated absolute risks of recurrent venous thromboembolism at six months. The population included 34,072 patients with active cancer and venous thromboembolism. Recurrence risks at six months were higher for patients with genitourinary cancer (6.5%), lung cancer (6.1%), gastrointestinal cancer (5.6%), brain cancer (5.2%), and hematological cancer (5.1%) than for patients with gynecological cancer (4.7%), breast cancer (4.1%), and other cancer types (4.8%). Recurrence risks were similar for men (5.2%) and women (4.9%), with and without chemotherapy (5.1%), across Ottawa risk score group (low: 5.0%; high: 5.1%) and across calendar periods but increased with increasing cancer stage. The overall six-month all-cause mortality risk was 26%, and highest for patients with lung cancer (49%) and lowest among breast cancer patients (4.1%). Six-month recurrence risk after first-time cancer-associated venous thromboembolism was high and varied by cancer type and patient characteristics. Refining risk stratification for recurrence may improve decision-making regarding treatment duration after cancer-associated thromboembolism. • Risk factors for recurrent venous thromboembolism in cancer are not well described. • Danish nationwide cohort study on recurrent cancer-associated venous thromboembolism. • The overall risk of recurrence at 6 months was 5.2%. • Risks were similar across sex and for patients with and without chemotherapy. • Risks were higher with increasing cancer stage. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of cancer-associated venous thromboembolism has increased, but whether short-term mortality after cancer-associated venous thromboembolism has changed remains uncertain. We investigated whether the increasing incidence of venous thromboembolism in cancer patients is associated with a change in mortality.Methods: We used administrative medical registries to identify a cohort of all Danish patients diagnosed with a first primary cancer from 2006 to 2017. We examined temporal changes in 1-year risks of venous thromboembolism and in mortality risks at 30 days and 1 year after venous thromboembolism. Cox regression was used to assess changes in mortality rate ratios over time.Results: We included 350,272 cancer patients (median age 68 years, 49.1% female), of whom 8167 developed venous thromboembolism within 1 year after cancer diagnosis. The cumulative 1-year risk of venous thromboembolism was 1.8% in 2006-2008, increasing to 2.8% for patients diagnosed in 2015-2017. The 30-day mortality after venous thromboembolism decreased from 15.1% in 2006-2008 to 12.7% in 2015-2017, and the 1-year mortality decreased from 52.4% to 45.8%, equivalent to a hazard ratio (HR) of 0.83 (95% confidence interval [CI], 0.75-0.90). This pattern of declining 1-year mortality was consistent for patients with pulmonary embolism, HR 0.79 (95% CI, 0.69-0.90), and deep venous thrombosis, HR 0.76 (95% CI, 0.67-0.87). Lower mortality over time was evident across all strata of cancer stage, cancer type, and cancer treatment.Conclusions: The 1-year risk of venous thromboembolism after a first primary cancer diagnosis in Denmark increased during 2006-2017. This increase was accompanied by declining mortality. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate potential predictors associated with not initiating anticoagulation after incident venous thromboembolism.Methods: We linked Danish nationwide health registries to identify all patients with incident venous thromboembolism from 2003 through 2016. We defined treatment noninitiation as not claiming a prescription for an anticoagulant drug within 30 days after hospital discharge. To identify potential predictors of noninitiation, relative risks (RRs) with 95% confidence intervals (CIs) were calculated adjusting for other compliance-related factors.Results: The study included 38,044 patients with incident venous thromboembolism (53.2% female and median age 66.1 years). Of these, 24.1% (n = 9294) were noninitiators. Demographic and condition-related factors that predicted noninitiation included: female sex (RR 1.30; 95% CI, 1.25-1.34), age <30 vs age >65 years (RR 1.18; 95% CI, 1.13-1.33), hospitalization 0-3 days vs >3 days (RR 1.96; 95% CI, 1.87-2.07), incident deep venous thrombosis (RR 1.91; 95% CI, 1.81-2.01), and unprovoked venous thromboembolism (RR 1.13; 95% CI, 1.08-1.17). Socioeconomic factors had less influence on risk of noninitiation. Individual chronic diseases predictive of noninitiation included congestive heart failure (RR 1.27; 95% CI, 1.17-1.37), ischemic heart disease (RR 1.20; 95% CI, 1.13-1.28), and liver disease (RR 1.60; 95% CI, 1.42-1.81).Conclusion: Up to one-fourth of patients diagnosed with incident venous thromboembolism did not initiate anticoagulant treatment within 30 days after hospital discharge. Identification of clinical predictors of noninitiation may enable implementation of patient-tailored strategies to improve adherence and thereby potentially prevent venous thromboembolism morbidity, mortality, and recurrence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]