Risk of stroke in male and female patients with atrial fibrillation in a nationwide cohort.

Female sex has been suggested as a risk modifier for stroke in patients with atrial fibrillation (AF) with comorbid prevalent stroke risk factors. Management has evolved over time towards a holistic approach that may have diminished any sex difference in AF-related stroke. In a nationwide cohort of AF patients free from oral anticoagulant treatment, we examine the time trends in stroke risk overall and in relation to risk differences between male and female patients. Here we show that among 158,982 patients with AF (median age 78 years (IQR: 71 to 85); 52% female) the 1-year thromboembolic risk was highest between 1997-2000 with a risk of 5.6% and lowest between 2013-2016 with a risk of 3.8%, declining over the last two decades. The excess stroke risk for female vs male patients has also been declining, with risk-score adjusted relative risk estimates suggesting limited sex-difference in recent years.

Positive predictive value and sensitivity of cancer-associated venous thromboembolism diagnoses in the Danish National Patient Register.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Validity of obstructive sleep apnoea diagnoses.

INTRODUCTION: Healthcare databases are a valuable source for epidemiological research in obstructive sleep apnoea, but accurately registered diagnoses are pivotal in contributing quality evidence. We examined positive predictive values (PPV) of the International Classification of Diseases, tenth version (ICD-10) diagnosis for "obstructive sleep apnoea" and "sleep apnoea" in the Danish National Patient Register. METHODS: Using the Danish National Patient Registry, we randomly sampled 100 patients from the North Denmark Region diagnosed with "obstructive sleep apnoea" (ICD-10 code DG4732) and 100 patients diagnosed with "sleep apnoea" (DG473*) during the year 2020. We calculated the PPV using a documented Apnea-Hypopnea Index (AHI) ≥ 5 to confirm the recorded diagnosis. A total of 70 patients were referred to the private sector for assessment of the AHI and excluded due to limited access to their data. RESULTS: The study population included 130 patients, among whom 64 were diagnosed with "obstructive sleep apnoea", and 66 patients were registered with "sleep apnoea". The PPV for "obstructive sleep apnoea" was 93.8% (95% confidence interval (CI): 85.0-97.5%), and the PPV for "sleep apnoea" was 80.3% (95% CI: 69.2-88.1%). CONCLUSIONS: Our findings indicated a high validity of the ICD-10 code DG4732 with a PPV of 93.8% and a lower PPV (80.3%) for the ICD-10 code DG473* for identifying patients with obstructive sleep. The "obstructive sleep apnoea" diagnosis is a suitable source of data for epidemiological research to identify patients with the disease. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Trends of Pulmonary Embolism-Related Sudden Cardiac Death in the United States, 1999-2019.

OBJECTIVES: Up-to-date population-based data on pulmonary embolism (PE)-related sudden cardiac death (SCD) mortality trends in the United States (US) are scant. We assess the current trends in PE-related SCD mortality in US over the past two decades and determine differences by sex, race, ethnicity, age, and census region. METHODS: We extracted PE-related SCD mortality rates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2019, in patients aged ≥ 15 years old. Age-adjusted mortality rates (AAMRs) were assessed using the Joinpoint regression modeling and expressed as estimated average annual percentage change (AAPC) with relative 95% confidence intervals (CIs). RESULTS: Between 1999 and 2019, the AAMR from acute PE-related SCD mortality in the US linearly increased [AAPC: +2.4% (95% CI: 2.2 to 2.6), p < 0.001)]. The AAMR increase was more pronounced in men [AAPC: +2.8% (95% CI: 2.6 to 2.9), p < 0.001], Whites [AAPC: +2.7% (95% CI: 2.3 to 3.1), p < 0.001], Latinx/Hispanic patients [AAPC:+2.0% (95% CI: 1.2 to 2.8), p < 0.001], subjects younger than 65 years [AAPC: +2.4% (95% CI: 2.1 to 2.6), p < 0.001] and in residents of rural areas [AAPC: +3.6% (95% CI: 3.3 to 3.9), p < 0.001]. Moreover, higher percentages of PE-related SCD and the relative absolute number of deaths were observed in the South compared with other geographical regions. CONCLUSIONS: PE-related SCD mortality in the US has increased over the last two decades. Stratification by race, ethnicity, urbanization, and census region demonstrates ethnoracial and regional disparities that require further investigation and remedy.

Risk of recurrent cancer-associated venous thromboembolism: A Danish nationwide cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Positive Predictive Value of Non-Traumatic Bleeding Diagnoses in the Danish National Patient Register.

Purpose: The majority of bleeding diagnoses in the Danish National Patient Registry have not been validated despite extensive use in epidemiological research. Therefore, we examined the positive predictive value (PPV) of non-traumatic bleeding diagnoses in the Danish National Patient Registry. Study Design: Population-based validation study. Patients and Methods: Based on a manual review of electronic medical records, we estimated the PPV of diagnostic coding (International Classification of Diseases, Tenth Revision (ICD-10)) for non-traumatic bleeding for all patients ≥65 years of age with any hospital contact in the North Denmark Region during March-December 2019 as registered in the Danish National Patient Registry. We calculated PPVs and associated 95% confidence intervals (CI) for non-traumatic bleeding diagnoses overall and stratified according to primary or secondary diagnosis, and according to major anatomical sites. Results: A total of 907 electronic medical records were available for review. The population mean age was 79.33 years (standard deviation (SD)=7.73) and 57.6% were males. Primary bleeding diagnoses accounted for 766 of the records and 141 were secondary bleeding diagnoses. The overall PPV for bleeding diagnoses was 94.0% (95% CI: 92.3-95.4). The PPV was 98.7% (95% CI: 97.6-99.3) for the primary diagnoses and 68.8% (95% CI: 60.7-75.9) for the secondary diagnoses. When stratified according to subgroups of major anatomical sites, the PPVs ranged between 94.1% and 100% for the primary diagnoses, and between 53.8% and 100% for secondary diagnoses. Conclusion: The overall validity of non-traumatic bleeding diagnoses in the Danish National Patient Registry is high and considered acceptable for epidemiological research. However, PPVs were substantially higher for primary than for secondary diagnosis.

Electrocardiographic P terminal force in lead V1, its components, and the association with stroke and atrial fibrillation or flutter.

BACKGROUND: The electrocardiographic (ECG) marker P terminal force V1 (PTFV1) is generally perceived as a marker of left atrial pathology and has been associated with atrial fibrillation or flutter (AF). OBJECTIVE: The purpose of this study was to determine the association between PTFV1 components (duration and amplitude) and incident AF and stroke/transient ischemic attack (TIA). METHODS: The study included patients with an ECG recorded at the Copenhagen General Practitioners Laboratory in 2001 to 2011. PTFV1 ≥4 mV·ms was considered abnormal. Patients with abnormal PTFV1 were stratified into tertiles based on duration (PTDV1) and amplitude (PTAV1) values. Cox regressions adjusted for age, sex, and relevant comorbidities were used to investigate associations between abnormal PTFV1 components and AF and stroke/TIA. RESULTS: Of 267,636 patients, 5803 had AF and 18,176 had stroke/TIA (follow-up 6.5 years). Abnormal PTFV1 was present in 44,549 subjects (16.7%) and was associated with an increased risk of AF and stroke/TIA. Among patients with abnormal PTFV1, the highest tertile of PTDV1 (78-97 ms) was associated with the highest risk of AF (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.23-1.52) and highest risk of stroke/TIA (HR 1.13; 95% CI 1.05 -1.20). For PTAV1, the highest tertile (78-126 µV) conferred the highest risk of AF and stroke/TIA (HR 1.20; 95% CI 1.09-1.32; and HR 1.21; 95% CI 1.14-1.25, respectively). CONCLUSION: Abnormal PTFV1 was associated with an increased risk of AF and stroke/TIA. Increasing PTDV1 showed a dose-response relationship with the development of AF and stroke/TIA, whereas the association between PTAV1 and AF was less apparent.

Long-Term Management of Pulmonary Embolism: A Review of Consequences, Treatment, and Rehabilitation.

The concept of pulmonary embolism is evolving. Recent and emerging evidence on the treatment of specific patient populations, its secondary prevention, long-term complications, and the unmet need for rehabilitation has the potential to change clinical practice for the benefit of the patients. This review discusses the recent evidence from clinical trials, observational studies, and guidelines focusing on anticoagulation treatment, rehabilitation, emotional stress, quality of life, and the associated outcomes for patients with pulmonary embolism. Guidelines suggest that the type and duration of treatment with anticoagulation should be based on prevalent risk factors. Recent studies demonstrate that an anticoagulant treatment that is longer than two years may be effective and safe for some patients. The evidence for extended treatment in cancer patients is limited. Careful consideration is particularly necessary for pulmonary embolisms in pregnancy, cancer, and at the end of life. The rehabilitation and prevention of unnecessary deconditioning, emotional distress, and a reduced quality of life is an important, but currently they are unmet priorities for many patients with a pulmonary embolism. Future research could demonstrate optimal anticoagulant therapy durations, follow-ups, and rehabilitation, and effective patient-centered decision making at the end of life. A patient preferences and shared decision making should be incorporated in their routine care when weighing the benefits and risks with primary treatment and secondary prevention.

Risk of Cerebrovascular Events in Intracerebral Hemorrhage Survivors With Atrial Fibrillation: A Nationwide Cohort Study.

BACKGROUND: In patients with intracerebral hemorrhage (ICH) and prevalent atrial fibrillation (AF), the optimal stroke prevention strategy is unclear. We sought to estimate the risk of cerebrovascular events among ICH survivors with AF. METHODS: We used the Danish Stroke Registry to identify patients with incident ICH and prevalent AF between 2003 and 2018. Key inclusion/exclusion criteria of the PRESTIGE-AF (Prevention of Stroke in Intracerebral hemorrhage Survivors With Atrial Fibrillation) trial were applied. Cumulative incidence of recurrent ICH, cerebrovascular ischemic event, and all-cause death were investigated after one year. RESULTS: A total of 1885 patients (median age 80.0 years; 47.6% females) were included in the study. We observed 191 cerebrovascular events and 650 all-cause deaths, and more cerebrovascular ischemic events (N=63) than recurrent ICH events (N=40). Risks of recurrent ICH, cerebrovascular ischemic event, and all-cause death were 1.5%, 3.2%, and 30.3%, respectively, among patients not exposed to OAC during follow-up. The cumulative incidences were 2.8% for recurrent ICH, 3.2% for cerebrovascular ischemic events, and 22.0% for all-cause death among patients initiating/resuming OAC during follow-up. CONCLUSIONS: We observed a high risk of cerebrovascular ischemic events and a very high risk of all-cause death at one year after the incident ICH. The results of ongoing clinical trials are warranted to determine optimal stroke prevention treatment among ICH survivors with concomitant AF.

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy.

The Khorana score is recommended for guiding primary venous thromboembolism (VTE) prophylaxis in cancer patients, but its clinical utility overall and across cancer types remains debatable. Also, some previous validation studies have ignored the competing risk of death, hereby potentially overestimating VTE risk. We identified ambulatory cancer patients initiating chemotherapy without other indications for anticoagulation using Danish health registries and estimated 6-month cumulative incidence of VTE stratified by Khorana levels. Analyses were conducted with and without considering death as a competing risk using the Kaplan-Meier method vs the cumulative incidence function. Analyses were performed overall and stratified by cancer types. Of 40 218 patients, 35.4% were categorized by Khorana as low risk (score 0), 53.6% as intermediate risk (score 1 to 2), and 10.9% as high risk (score ≥3). Considering competing risk of death, the corresponding 6-month risks of VTE were 1.5% (95% confidence interval [CI], 1.3-1.7), 2.8% (95% CI, 2.6-3.1), and 4.1% (95% CI, 3.5-4.7), respectively. Among patients recommended anticoagulation by guidelines (Khorana score ≥2), the 6-month risk was 3.6% (95% CI, 3.3-3.9). Kaplan-Meier analysis overestimated incidence up to 23% compared with competing risk analyses. Using the guideline-recommended threshold of ≥2, the Khorana score did not risk-stratify patients with hepatobiliary or pancreatic cancer, lung cancer, and gynecologic cancer. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to the risk of VTE, but not for all cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials.

Effectiveness and Safety of NOAC Versus Warfarin in Patients With Atrial Fibrillation and Aortic Stenosis.

Background Guideline recommendations on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with aortic stenosis are based on studies including a low number of patients with aortic stenosis. The aim of this study was to estimate the effects of NOAC versus warfarin on thromboembolism and major bleeding among AF patients with aortic stenosis. Methods and Results We emulated a target trial using observational data from Danish nationwide registries between 2013 and 2018. Thromboembolism was defined as a hospital diagnosis of ischemic stroke and/or systemic embolism, and major bleeding was defined as a hospital diagnosis of intracranial bleeding, gastrointestinal bleeding, or major or clinically relevant bleeding in other anatomic sites. Treatment effect estimates were based on an intention-to-treat and per-protocol approach. A total of 3726 patients with AF and aortic stenosis claimed a prescription for either a NOAC (2357 patients) or warfarin (1369 patients) and met the eligibility criteria for the trial. During 3 years of follow-up, the adjusted hazard ratios for thromboembolism and major bleeding were 1.62 (95% CI, 1.08-2.45) and 0.73 (0.59-0.91) for NOAC compared with warfarin in the intention-to-treat analyses. Similar results were observed in the per-protocol analyses. Conclusions In this observational study, we observed a higher risk of thromboembolism but a lower risk of major bleeding for treatment with NOACs compared with warfarin in patients with AF and aortic stenosis. This observation needs confirmation in large randomized trials in these commonly encountered patients.

Management of Cancer-Associated Venous Thrombosis: A Nationwide Survey among Danish Oncologists.

Background Treatment patterns for cancer-associated venous thrombosis (CAT) has been shown to be nonconsistent with contemporary guideline recommendations, resulting in poor patient outcomes. Objectives The study aimed to describe contemporary CAT management in Danish oncology departments and identify knowledge gaps and inconsistencies between guidelines and clinical practice. Patients and Methods A survey questionnaire in Danish was developed based on contemporary national guidelines. Using an open recruitment strategy, invitations to participate in the electronic survey were sent to physicians employed at oncology departments in Denmark in winter of 2018/2019. The questionnaire was based on current national guidelines and included 10 items with multiple choices and a free-text option to specify or comment. The questionnaire was pilot-tested by a junior and senior oncologist. Results A total of 142 physicians completed the survey, representing all Danish geographical regions and various seniority. The majority reported that CAT was treated and followed up in oncology departments. However, 36.6% of the physicians were unaware of the existence of designated cancer thrombosis guidelines. Risk of venous thrombosis was generally assessed without diagnostic scores. Almost all (98.6%) reported low-molecular-weight heparin to be first-line treatment for CAT. Treatment duration seemed wrongly influenced by subtype of venous thrombosis, and 44.5% responded that thromboprophylaxis among hospitalized patients was substantially underused. Conclusion The variability in the daily clinical management of CAT demonstrated through this survey indicates a potential to increase awareness of available guidelines, standardized use of inpatient thromboprophylaxis, and organized treatment and follow-up in a multidisciplinary setting, which would potentially improve management of CAT in Denmark.

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.

Thromboembolism and bleeding complications in anticoagulated patients with atrial fibrillation and native aortic or mitral valvular heart disease: a descriptive nationwide cohort study.

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.

Should We Reintroduce Previous Venous Thromboembolism Into Decision-Making for Anticoagulation in Atrial Fibrillation?

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.

Thromboembolic Risk in Nonanticoagulated Patients With Atrial Fibrillation and Valvular Heart Disease.

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 CHA2DS2-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 CHA2DS2-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 CHA2DS2-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.

Cancer-associated venous thromboembolism and the non-vitamin K antagonist oral anticoagulants: a review of clinical outcomes and patient perspectives.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

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.

Female Sex as a Risk Modifier for Stroke Risk in Atrial Fibrillation: Using CHA2DS2-VASc versus CHA2DS2-VA for Stroke Risk Stratification in Atrial Fibrillation: A Note of Caution.

Stroke prevention is a key clinical concern in the management of patients with atrial fibrillation. Oral anticoagulation treatment reduces the risk of disabling stroke, but the treatment increases the risk of bleeding. For decades, the decision to initiate oral anticoagulation has been guided by clinical risk scoring systems such as the CHADS2 and CHA2DS2-VASc scores. In this narrative review, we focus on the recent discussion of the "Sc" (Sex Category) criterion in the CHA2DS2-VASc score. Epidemiological considerations when assessing stroke rates in cohorts are discussed, and the implications of different methodological approaches are outlined. Next, we review studies investigating the association of the "Sc" criterion on the stroke rates under various approaches. Lastly, we discuss potential consequences of implementing the recently suggested sex-less CHA2DS2-VA score, which leaves out female sex from stroke risk assessment in atrial fibrillation.

Incidence and prognostic factors for recurrence of intracerebral hemorrhage in patients with and without atrial fibrillation: A cohort study.

BACKGROUND: Intracerebral hemorrhage is a devastating vascular event. Clinical factors prognostic of recurrence facilitating individualized post-bleeding patient management are sparsely described. We aimed to describe incidence of recurrence of intracerebral hemorrhage and explore the prognostic value of 25 clinical characteristics in patients with and without atrial fibrillation. METHODS: Cohort study of patients with incident intracerebral hemorrhage diagnosed from 2003 to 2016 identified using nationwide Danish administrative registries. Results reported as cumulative incidence of intracerebral recurrence accounting for competing risk of death. Univariate and multivariate prognostic factors for recurrence estimated using Cox regression (hazard ratios [HRs], 95% confidence intervals [CI]). RESULTS: We identified 9255 patients with incident intracerebral hemorrhage (median age 73 years, 46.6% females, 16% with atrial fibrillation). Five-year risks of recurrence of intracerebral hemorrhage were approximately 10% in the study population, although slightly higher for patients without atrial fibrillation. Prognostic factors for recurrence were broadly similar for patients with and without atrial fibrillation. Age in categories <60 years (reference), age 60-70 years (HR 1.29, 95% CI 1.02-1.64), age 70-80 years (HR 1.59, 95% CI 1.26-2.00), age >80 years (HR 1.19, 95% CI 0.91-1.55), nursing home residency (HR 1.48, 95% CI 1.02-2.13), and Scandinavian Stroke Scale score ('mild' versus 'moderate' (HR 1.40, 95% CI 1.13-1.72) and 'severe' (HR 1.96, 95% CI 1.61-2.39)) were the strongest prognostic factors. CONCLUSION: Risk of recurrence of intracerebral hemorrhage after five years was approximately 10%. Clinical characteristics associated with recurrence were few and broadly similar for patients with and without atrial fibrillation, with age and measure of incident bleeding severity, as reflected by Scandinavian Stroke Scale score, being the most important.