Increasing Incidence and Declining Mortality After Cancer-Associated Venous Thromboembolism: A Nationwide Cohort Study.

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.

Development of Sex-Stratified Prediction Models for Recurrent Venous Thromboembolism: A Danish Nationwide Cohort Study.

OBJECTIVE: To optimize decision making for anticoagulant treatment duration after incident venous thromboembolism, we derived and internally validated two clinically applicable sex-specific prediction models for venous thromboembolism recurrence, discarding the traditional categorization of provoked and unprovoked venous thromboembolism. METHODS: This study was based on data from Danish nationwide registries. We identified all routine care in- and outpatients with completed anticoagulant treatment for incident venous thromboembolism from 2012 through 2017. The outcome was recurrent venous thromboembolism within 2 years. Risk scores were derived using Cox regression analysis and a backward selection process on a set of 24 potential predictors. Performance was assessed through calibration and discrimination using bootstrap techniques to internally validate the scores. RESULTS: The study included 11,519 patients. Risk scores under the joint acronym AIM-SHA-RP were developed. Age, Incident pulmonary embolism, and recent Major surgery were predictors for both sexes; Statin treatment, Heart disease and Antiplatelet treatment were predictors specifically for men, while chronic Renal disease and recent Pneumonia or sepsis were predictors specifically for women. The risk scores were well calibrated and identified a low- (< 5%), intermediate- (5-10%), and high-risk (> 10%) group for both sexes. Generally, discriminative capacities, as measured by the c-statistic, were limited. CONCLUSION: We developed two clinically applicable risk scores to estimate the risk of recurrent venous thromboembolism after completed anticoagulant treatment. The risk scores can potentially guide treatment duration of anticoagulation after incident venous thromboembolism but require further external validation before implemented in clinical practice.

Predictors of Not Initiating Anticoagulation After Incident Venous Thromboembolism: A Danish Nationwide Cohort Study.

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.

Mortality in Patients With Atrial Fibrillation Receiving Nonrecommended Doses of Direct Oral Anticoagulants.

BACKGROUND: The recommended doses for direct oral anticoagulants (DOACs) to prevent stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) are described in specific regulatory authority approvals. OBJECTIVES: The impact of DOAC dosing, according to the recommended guidance on all-cause mortality, stroke/SE, and major bleeding, was assessed at 2-year follow-up in patients with newly diagnosed AF. METHODS: Of a total of 34,926 patients enrolled (2013 to 2016) in the prospective GARFIELD-AF (Global Anticoagulant Registry in the FIELD-AF), 10,426 patients received a DOAC. RESULTS: The majority of patients (72.9%) received recommended dosing, 23.2% were underdosed, and 3.8% were overdosed. Nonrecommended dosing (underdosage and overdosage combined) compared with recommended dosing was associated with a higher risk of all-cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.48); HR: 1.25 (95% CI: 1.04 to 1.50) for underdosing, and HR: 1.19 (95% CI: 0.83 to 1.71) for overdosing. The excess deaths were cardiovascular including heart failure and myocardial infarction. The risks of stroke/SE and major bleeding were not significantly different irrespective of the level of dosing, although underdosed patients had a significantly lower risk of bleeding. A nonsignificant trend to higher risks of stroke/SE (HR: 1.51; 95% CI: 0.79 to 2.91) and major bleeding (HR: 1.29; 95% CI: 0.59 to 2.78) was observed in patients with overdosing. CONCLUSIONS: In GARFIELD-AF, most patients received the recommended DOAC doses according to country-specific guidelines. Prescription of nonrecommended doses was associated with an increased risk of death, mostly cardiovascular death, compared with patients on recommended doses, after adjusting for baseline factors. (Global Anticoagulant Registry in the Field-AF [GARFIELD-AF]; NCT01090362).

Psychotropic drug use following venous thromboembolism versus diabetes mellitus in adolescence or young adulthood: a Danish nationwide cohort study.

OBJECTIVES: Critical and chronic illness in youth such as diabetes can lead to impaired mental health. Despite the potentially traumatic and life-threatening nature of venous thromboembolism (VTE), the long-term mental health of adolescents and young adults with VTE is unclear. We compared the long-term mental health of adolescents and young adults with VTE versus adolescents and young adults with insulin-dependent diabetes mellitus (IDDM) using psychotropic drug purchase as proxy for mental health. DESIGN: Nationwide registry-based cohort study. SETTING: Denmark 1997-2015. PARTICIPANTS: All patients aged 13-33 years with an incident diagnosis of VTE (n=5065) or IDDM (n=6609). EXPOSURE: First time primary hospital diagnosis of VTE or IDDM. PRIMARY AND SECONDARY OUTCOME MEASURES: Adjusted absolute risk and risk difference at 1 and 5 years follow-up for first psychotropic drug purchase comparing patients with VTE and patients with IDDM. RESULTS: The absolute 1 year risk of psychotropic drug use was 6.2% among VTE patients versus 3.6% among patients with IDDM, at 5 years this was 19.3%-14.7%, respectively. After adjusting for the effect of sex, age and risk factors for VTE this corresponded to a 1 year risk differences of 1.9% (95 % CI 0.1% to 3.3%). At 5 years follow-up the risk difference was 1.9% (95% CI 0.5% to 3.3%). CONCLUSION: One-fifth of adolescents and young adults with incident VTE had claimed a prescription for a psychotropic drug within 5 years, a risk comparable to that of young patients with IDDM.

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.