Initial hemodynamic status and Acute Mortality in Cancer patients with Acute Pulmonary Embolism: from the COMMAND VTE Registry.

BACKGROUND: Initial hemodynamic status in patients with acute pulmonary embolism (PE) concerns their acute clinical outcomes. Nevertheless, the characteristics of initial hemodynamic dysfunction and acute mortality in PE patients with active cancer is still controversial. METHODS: We analyzed the data of 1715 PE patients in the COMMAND VTE Registry to compare initial hemodynamic dysfunction, management strategies, and mortality outcomes at 30 days after PE diagnosis between patients with and without active cancer (N = 393 and N = 1322). RESULTS: The patients with active cancer showed lower prevalence of right ventricular dysfunction (35.4% vs. 49.5%, P < 0.001), shock (6.4% vs. 11.6%, P = 0.003), and cardiac arrest (1.8% vs. 5.5%, P = 0.002) at PE diagnosis, compared with those without. The patients with active cancer less frequently received systemic thrombolysis (4.1% vs. 12.6%, P < 0.001) than those without. There was no significant difference in the cumulative 30-day incidence of PE-related death between patients with and without active cancer (4.1% vs. 4.2%, P = 0.89). The cumulative 30-day incidence of all-cause death was significantly higher in patients with active cancer than in those without (11.5% vs. 4.9%, P < 0.001). CONCLUSIONS: PE patients with active cancer less frequently present with initial hemodynamic dysfunction at PE diagnosis, compared with those without. Nevertheless, PE patients with active cancer still show a similar risk of PE-related death and a higher risk of all-cause death at 30 days after PE diagnosis, suggesting the importance of prudent management for this patient population even if their initial hemodynamic status are not compromised.

Statins use and recurrent venous thromboembolism in the direct oral anticoagulant era: insight from the COMMAND VTE Registry-2.

Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45-0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59-1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era.

External Validation of the Japanese Clinical Score for Mortality Prediction in Patients With Acute Heart Failure.

BACKGROUND: To predict mortality in patients with acute heart failure (AHF), we created and validated an internal clinical risk score, the KICKOFF score, which takes physical and social aspects, in addition to clinical aspects, into account. In this study, we validated the prediction model externally in a different geographic area.Methods and Results: There were 2 prospective multicenter cohorts (1,117 patients in Osaka Prefecture [KICKOFF registry]; 737 patients in Kochi Prefecture [Kochi YOSACOI study]) that had complete datasets for calculation of the KICKOFF score, which was developed by machine learning incorporating physical and social factors. The outcome measure was all-cause death over a 2-year period. Patients were separated into 3 groups: low risk (scores 0-6), moderate risk (scores 7-11), and high risk (scores 12-19). Kaplan-Meier curves clearly showed the score's propensity to predict all-cause death, which rose independently in higher-risk groups (P<0.001) in both cohorts. After 2 years, the cumulative incidence of all-cause death was similar in the KICKOFF registry and Kochi YOSACOI study for the low-risk (4.4% vs. 5.3%, respectively), moderate-risk (25.3% vs. 22.3%, respectively), and high-risk (68.1% vs. 58.5%, respectively) groups. CONCLUSIONS: The unique prediction score may be used in different geographic areas in Japan. The score may help doctors estimate the risk of AHF mortality, and provide information for decisions regarding heart failure treatment.

Risk factors of thrombotic recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism.

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97-14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56-7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36-3.07), men (HR 1.52, 95% CI 1.02-2.27), history of major bleeding (HR 3.48, 95% CI 1.82-6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04-6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. CLINICAL TRIAL REGISTRATION: Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

Periprocedural management and clinical outcomes of invasive procedures after venous thromboembolism: from the COMMAND VTE registry.

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847-1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

Clinical characteristics and outcomes of patients with venous thromboembolism according to diagnosis on weekends versus on weekdays.

There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P < 0.001), and with more severe hemodynamic condition for PE patients. The patients diagnosed on weekends more often received initial parenteral anticoagulation therapy and thrombolysis than those diagnosed on weekdays. The cumulative 30-day incidence of all-cause death was not significantly different between the two groups among PE patients (diagnosis on weekends: 6.2% vs. diagnosis on weekdays: 6.5%, P = 0.87), as well as among DVT patients (0.0% vs. 1.5%, P = 0.24). The most frequent cause of deaths was fatal PE in both groups among PE patients. The risks for recurrent VTE and major bleeding at 30-day were not significantly different between the 2 groups among PE patients, nor among DVT only patients. In conclusion, the VTE patients diagnosed on weekends presented more often with PE, and with more severe condition for PE patients. Nevertheless, the risk for 30-day mortality was not significantly different between patients diagnosed on weekends and on weekdays.

The clinical characteristics and outcomes of heart failure patient with chronic obstructive pulmonary disease from the Japanese community-based registry.

Both heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common diseases, but few studies have assessed the relationship between COPD and outcomes in patients with acute HF, especially in relation to age or ejection fraction (EF). The Kitakawachi Clinical Background and Outcome of Heart Failure Registry was a prospective, multicenter, community-based cohort and enrolled a total of 1,102 patients with acute HF between 2015 and 2017 in this study. The primary endpoint was defined as a composite endpoint that included all-cause mortality and hospitalization for HF. We stratified patients into two groups: those aged ≥ 80 years (elderly) and < 80 years (nonelderly). HF with preserved EF (HFpEF) was defined as EF ≥ 50%, whereas HF with reduced ejection fraction (HFrEF) was defined as EF < 50%. A total of 159 patients (14.4%) with COPD and 943 patients (83.6%) without COPD were included. COPD was found to be independently associated with a higher risk of the composite endpoint (adjusted hazard ratio: 1.42, 95% confidence interval: 1.14-1.77; p = 0.003). During a subgroup analysis, COPD was exposed as an independent risk factor of the composite endpoint in nonelderly patients; however, there was not such a finding observed among elderly patients. Separately, there was a significant association with COPD and the composite endpoint in patients with HFpEF. COPD showed a significantly higher risk of the composite endpoint after discharge in acute HF. However, this heightened risk was observable only in the subgroup of nonelderly patients and those of HFpEF.

Clinical Characteristics and Outcomes of Heart Failure Patients With Long-Term Care Insurance　- Insights From the Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

BACKGROUND: In Japan, the long-term care insurance (LTCI) system has an important role in helping elderly people, but there have been no clinical studies that have examined the relationship between the LTCI and prognosis for patients with acute heart failure (HF).Methods and Results:This registry was a prospective multicenter cohort, 1,253 patients were enrolled and 965 patients with acute HF aged ≥65 years were comprised the study group. The composite endpoint included all-cause death and hospitalization for HF after discharge. We divided the patients into 4 groups: (i) patients without LTCI, (ii) patients requiring support level 1 or 2, (iii) patients with care level 1 or 2, and (iv) patients with care levels 3-5. The Kaplan-Meier analysis identified a lower rate of the composite endpoint in group (i) than in the other groups. After adjusting for potentially confounding effects using a Cox proportional regression model, the hazard ratio (HR) of the composite endpoint increased significantly in groups (iii) and (iv) (adjusted HR, 1.62; 95% confidence interval [CI], 1.22-1.98 and adjusted HR, 1.62; 95% CI, 1.23-2.14, respectively) when compared with group (i). However, there was no significant difference between groups (i) and (ii). CONCLUSIONS: The level of LTCI was associated with a higher risk of the composite endpoint after discharge in acute HF patients.

Risk Factors for Major Bleeding During Anticoagulation Therapy in Cancer-Associated Venous Thromboembolism　- From the COMMAND VTE Registry.

BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22-7.85, P<0.001), chronic kidney disease (adjusted HR, 1.89; 95% CI 1.06-3.37, P=0.031), and gastrointestinal cancer (adjusted HR, 1.78; 95% CI, 1.04-3.04, P=0.037) were independently associated with an increased risk of major bleeding. CONCLUSIONS: Major bleeding events were common during anticoagulation therapy in real-world cancer-associated VTE patients. Terminal cancer, chronic kidney disease, and gastrointestinal cancer were the independent risk factors for major bleeding.

D-dimer levels at diagnosis and long-term clinical outcomes in venous thromboembolism: from the COMMAND VTE Registry.

The relationship between D-dimer level at diagnosis and long-term clinical outcomes has not been fully evaluated in venous thromboembolism (VTE). The COMMAND VTE Registry is a multicenter registry enrolling consecutive acute symptomatic VTE patients in Japan. Patients with available D-dimer levels at diagnosis (N = 2852) were divided into 4 groups according to the D-dimer levels; Quartile 1 (0.0-4.9 µg/mL): N = 682, Quartile 2 (5.0-9.9 µg/mL) N = 694, Quartile 3 (10.0-19.9 µg/mL) N = 710, and Quartile 4 (≥ 20.0 µg/mL): N = 766. The cumulative incidence of all-cause death was higher in Quartile 4 throughout the entire follow-up period (19.9%, 24.9%, 28.8%, and 41.5% at 5-year, P < 0.0001), as well as both within and beyond 30-day. After adjustment, the excess risk of Quartile 4 relative to Quartile 1 for all-cause death remained significant (HR 1.60, 95% CI 1.29-2.03). Similarly, the excess risk of Quartile 4 relative to Quartile 1 for recurrent VTE was significant (HR 1.57, 95% CI 1.02-2.41), which was more prominent in the cancer subgroup. The dominant causes of death in Quartile 4 were pulmonary embolism within 30-day, and cancer beyond 30-day. In conclusions, in VTE patients, elevated D-dimer levels at diagnosis were associated with the increased risk for both short-term and long-term mortality. The higher mortality risk of patients with highest D-dimer levels was driven by the higher risk for fatal PE within 30-day, and by the higher risk for cancer death beyond 30-day. Elevated D-dimer levels were also associated with the increased risk for long-term recurrent VTE, which was more prominent in patients with active cancer.

Living Alone and Gender Differences in Rehospitalization for Heart Failure After Discharge Among Acute Heart Failure Patients.

Home treatment for heart failure (HF) is one of the most important problems in patients after discharge as a secondary preventive measure for rehospitalization for HF. However, there are no detailed studies on gender differences in sociopsychological factors such as living alone for HF rehospitalization among patients with acute HF (AHF).This prospective multicenter cohort study enrolled patients with AHF between April 2015 and August 2017. Patients of each gender with first AHF were divided into those living alone and those not living alone. The primary endpoint was defined as rehospitalization for HF after discharge. Cox proportional hazard analysis was performed to determine the association between living alone and the endpoint.Overall, 581 patients were included in this study during the 3-year follow-up. The proportion of rehospitalization for HF was significantly higher in patients living alone than in those not living alone among male patients. However, female patients showed no difference in endpoints between the two groups. The difference was independently maintained even after adjusting for differences in social backgrounds in male patients (adjusted hazard ratio (HR) 2.02; 95% confidence interval (CI), 1.07-3.70). In female patients, the HR for rehospitalization for HF showed no difference between the two groups (adjusted HR, 0.99; 95% CI, 0.56-1.69).In this study population, male patients living alone after first AHF discharge had a higher risk of rehospitalization for HF than those not living alone, but these differences were not observed in female patients.

Clinical Characteristics and Outcomes of Venous Thromboembolisms According to an Out-of-Hospital vs. In-Hospital Onset　- From the COMMAND VTE Registry.

BACKGROUND: Differences in the clinical characteristics and outcomes of venous thromboembolisms (VTEs) based on different clinical situations surrounding the onset might be important for directing appropriate treatment strategies, but have not yet been appropriately evaluated. Methods and Results: The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTEs in Japan between January 2010 and August 2014. We divided the study population into 3 groups: Out-of-hospital onset (n=2,308), In-hospital onset with recent surgery (n=310), and In-hospital onset without recent surgery (n=374). Active cancer was most prevalent in the In-hospital onset without recent surgery group, and least in the Out-of-hospital onset group (Out-of-hospital onset group: 20%, In-hospital onset with recent surgery group: 26%, and In-hospital onset without recent surgery group: 38%, P<0.001). The cumulative 5-year incidence of recurrent VTEs did not significantly differ across the 3 groups (11.4%, 5.8%, and 8.7%, respectively; P=0.11). The cumulative 5-year incidences of major bleeding and all-cause death were highest in the In-hospital onset without recent surgery group (11.1%, 8.5%, and 23.3%, P<0.001; 26.8%, 24.9%, and 48.4%, P<0.001, respectively). CONCLUSIONS: In the real-world VTE registry, the clinical characteristics and long-term outcomes substantially differed according to the clinical situation of VTE onset, suggesting the need for different treatment strategies for VTEs in different clinical settings.

Sex Differences in Clinical Characteristics and Outcomes of Patients With Venous Thromboembolism　- From the COMMAND VTE Registry.

BACKGROUND: It remains controversial whether sex category is a risk for recurrent venous thromboembolism (VTE) and major bleeding among VTE patients.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive acute symptomatic VTE patients from 29 centers in Japan between January 2010 and August 2014. We compared the clinical characteristics and outcomes of men and women. Men accounted for 1,169 (39%) and women 1,858 (61%). Compared with women, men were younger (64.9±14.7 vs. 68.6±15.6 years old, P<0.001), more often had prior VTE (7.2% vs. 5.1%, P=0.02), and less often had transient risk factors for VTE (30% vs. 40%, P<0.001). The proportions of active cancer and pulmonary embolism were comparable between men and women (24% vs. 22%, P=0.26; 56% vs. 57%, P=0.48, respectively). The cumulative 3-year incidences of recurrent VTE, major bleeding, and all-cause death were not significantly different between men and women (7.0% vs. 8.6%, P=0.47; 10.6% vs. 9.2%, P=0.25; 25.2% vs. 23.4%, P=0.35, respectively). The adjusted risks of men relative to women for recurrent VTE and for major bleeding remained insignificant (HR 0.83, 95% CI 0.63-1.09, P=0.17; HR 1.15, 95% CI 0.90-1.47, P=0.25, respectively). CONCLUSIONS: In real-world VTE patients, the clinical characteristics differed between men and women, but there was not a large sex-related difference in the risks for recurrent VTE or major bleeding.

Cancer-Associated Venous Thromboembolism in the Real World　- From the COMMAND VTE Registry.

BACKGROUND: There is a paucity of data on the management and prognosis of cancer-associated venous thromboembolism (VTE), leading to uncertainty about optimal management strategies.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive acute symptomatic VTE patients in Japan between 2010 and 2014. We divided the entire cohort into 3 groups: active cancer (n=695, 23%), history of cancer (n=243, 8%), and no history of cancer (n=2089, 69%). The rate of anticoagulation discontinuation was higher in patients with active cancer (43.5%, 27.0%, and 27.0%, respectively, at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding, and all-cause death were higher in patients with active cancer (recurrent VTE: 17.7%, 10.2%, and 8.6%, P<0.001; major bleeding: 26.6%, 8.8%, and 9.3%, P<0.001; all-cause death: 73.1%, 28.6%, 14.6%, P<0.001). Among the 4 groups classified according to active cancer status, the cumulative 1-year incidence of recurrent VTE was higher in the metastasis group (terminal stage group: 6.4%, metastasis group: 22.1%, under chemotherapy group: 10.8%, and other group: 5.8%, P<0.001). CONCLUSIONS: In a current real-world VTE registry, patients with active cancer had higher risk for VTE recurrence, bleeding, and death, with variations according to cancer status, than patients without active cancer. Anticoagulation therapy was frequently discontinued prematurely in patients with active cancer in discordance with current guideline recommendations.

Thrombolysis with tissue plasminogen activator in patients with acute pulmonary embolisms in the real world: from the COMMAND VTE registry.

There is still uncertainty about the optimal usage of thrombolysis for acute pulmonary embolisms (PEs), leading to a widely varying usage in the real world. The COMMAND VTE Registry is a multicenter retrospective registry enrolling consecutive patients with acute symptomatic venous thromboembolisms (VTEs) in Japan. The present study population consisted of 1549 patients with PEs treated with tissue plasminogen activator (t-PA) thrombolysis (N = 180, 12%) or without thrombolysis (N = 1369). Thrombolysis with t-PA was implemented in 33% of patients with severe PEs, and 9.2% of patients with mild PEs with a wide variation across the participating centers. Patients with t-PA thrombolysis were younger, and less frequently had active cancer, history of major bleeding, and anemia. At 30 days, t-PA thrombolysis as compared to no thrombolysis was associated with similar mortality rates (5.0% vs. 6.9%, P = 0.33), but a lower adjusted mortality risk (OR 0.41; 95% CI 0.18-0.90, P = 0.03), while it was associated with a trend for higher rates of major bleeding (5.6% vs. 2.9%, P = 0.06) and a significantly higher adjusted risk for major bleeding (OR 2.39; 95% CI 1.06-5.36, P = 0.03). In patients with severe PEs, the mortality rates at 30 days were significantly lower in the t-PA thrombolysis group than no thrombolysis group (15% vs. 37%, P = 0.006). In the present real-world VTE registry in Japan, t-PA thrombolysis was not infrequently implemented, not only in patients with severe PEs, but also in patients with mild PEs. A substantial mortality risk reduction might be suggested with t-PA thrombolysis in patients with severe PEs.

Influence of baseline anemia on long-term clinical outcomes in patients with venous thromboembolism: from the COMMAND VTE registry.

The influence of anemia on the long-term clinical outcomes has not been fully evaluated in patients with venous thromboembolism (VTE). We evaluated the influence of anemia among 3012 patients in the COMMAND VTE Registry with a median follow-up period of 1219 days. The outcomes measures were ISTH major bleeding, recurrent VTE and all-cause death. There were 1012 patients (34%) with moderate/severe anemia (Hb ≤ 10.9 g/dl), 615 patients (20%) with mild anemia (Hb 11.0-12.9 g/dl for men, and 11.0-11.9 g/dl for women), and 1385 patients (46%) without anemia. The cumulative 5-year incidence of major bleeding was significantly higher in patients with anemia (moderate/severe anemia: 17.6%, mild anemia: 12.1%, and no anemia: 8.7%, P < 0.001). After adjusting the confounders, the excess risk of mild and moderate/severe anemia, respectively, relative to no anemia for major bleeding remained significant (mild: adjusted HR 1.41: [95% CI 1.00-1.98], P = 0.048; moderate/severe: adjusted HR 1.91: [95% CI 1.42-2.58], P < 0.001, respectively). The excess risk of moderate/severe anemia relative to no anemia was also significant for mortality (adjusted HR 2.89: 95% CI 2.45-3.42, P < 0.001), but the risk was neutral for recurrent VTE (adjusted HR 1.05: 95% CI 0.76-1.45, P = 0.77). In conclusions, VTE patients with mild and moderate/severe anemia had higher risk for major bleeding events without significant excess risk for recurrent VTE events, and the risk for major bleeding events increased according to the severity of anemia. We should pay more attention to the optimal intensity and duration of anticoagulation in VTE patients with anemia.

Risk factors for post-thrombotic syndrome in patients with deep vein thrombosis: from the COMMAND VTE registry.

Post-thrombotic syndrome (PTS) is the most common chronic complication of deep vein thrombosis (DVT). Identifying high-risk patients for the development of PTS might be useful for its prevention. The COMMAND VTE Registry is a multicenter registry that enrolled 3027 consecutive patients with acute symptomatic venous thromboembolisms (VTEs) in Japan between January 2010 and August 2014. The current study population consisted of 1298 patients with lower extremities DVTs who completed 3-year follow-up for those who developed PTS and those without PTS. We investigated risk factors for the development of PTS at the time of DVT diagnosis, using a multivariable logistic regression analysis. Of the entire 1298 study patients, 169 (13%) patients were diagnosed with PTS within 3 years. The rate for anticoagulation discontinuation during follow-up was not significantly different between those with and without PTS. Chronic kidney disease (OR 2.21, 95% CI 1.45-3.39, P < 0.001), leg swelling (OR 4.15, 95% CI 2.25-7.66, P < 0.001), absence of transient risk factors for VTEs (OR 2.39, 95% CI 1.55-3.67, P < 0.001), active cancer (OR 3.66, 95% CI 2.30-5.84, P < 0.001), and thrombophilia (OR 2.07, 95% CI 1.06-4.04, P = 0.03) were independent risk factors for the development of PTS. In this real-world Japanese DVT registry, we could identify several important risk factors for the development of PTS at the time of DVT diagnosis.

Anticoagulation Therapy for Venous Thromboembolism in the Real World　- From the COMMAND VTE Registry.

BACKGROUND: Venous thromboembolism (VTE) has a long-term risk of recurrence, which can be prevented by anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE between January 2010 and August 2014. The entire cohort was divided into the transient risk (n=855, 28%), unprovoked (n=1,477, 49%), and cancer groups (n=695, 23%). The rate of anticoagulation discontinuation was highest in the cancer group (transient risk: 37.3% vs. unprovoked: 21.4% vs. cancer: 43.5% at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding and all-cause death were highest in the cancer group (recurrent VTE: 7.9% vs. 9.3% vs. 17.7%, P<0.001; major bleeding: 9.0% vs. 9.4% vs. 26.6%, P<0.001; and all-cause death: 17.4% vs. 15.3% vs. 73.1%, P<0.001). After discontinuation of anticoagulation therapy, the cumulative 3-year incidence of recurrent VTE was lowest in the transient risk group (transient risk: 6.1% vs. unprovoked: 15.3% vs. cancer: 13.2%, P=0.001). The cumulative 3-year incidence of recurrent VTE beyond 1 year was lower in patients on anticoagulation than in patients off anticoagulation at 1 year in the unprovoked group (on: 3.7% vs. off: 12.2%, P<0.001), but not in the transient risk and cancer groups (respectively, 1.6% vs. 2.5%, P=0.30; 5.6% vs. 8.6%, P=0.44). CONCLUSIONS: The duration of anticoagulation therapy varied widely in discordance with current guideline recommendations. Optimal duration of anticoagulation therapy should be defined according to the risk of recurrent VTE and bleeding as well as death.

Clinical Characteristics and Social Frailty of Super-Elderly Patients With Heart Failure　- The Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

BACKGROUND: Social background is important in preventing admission/readmission of heart failure (HF) patients. However, few clinical studies have been conducted to assess the social background of these patients, especially elderly patients.Methods and Results:The Kitakawachi Clinical Background and Outcome of Heart Failure (KICKOFF) Registry is a prospective multicenter community-based cohort of HF patients, established in April 2015. We compared the clinical characteristics and social background of the super-elderly group (≥85 years old) and the non-super-elderly group (<85 years old). This study included 647 patients; 11.8% of the super-elderly patients were living alone, 15.6% were living with only a partner, and of these, only 66.7% had the support of other family members. The super-elderly group had less control over their diet and drug therapies than the non-super-elderly group. Most patients in the super-elderly group were registered for long-term care insurance (77.4%); 73.5% of the super-elderly patients could walk independently before admission, but only 55.5% could walk independently at discharge, whereas 94% of the non-super-elderly patients could walk independently before admission and 89.4% could walk independently at discharge. CONCLUSIONS: The KICKOFF Registry provides unique detailed social background information of Japanese patients with HF. Super-elderly patients are at serious risk of social frailty; they need the support of other people and their ability to perform activities of daily living decline when hospitalized.

Incidence of Stroke or Systemic Embolism in Paroxysmal Versus Sustained Atrial Fibrillation: The Fushimi Atrial Fibrillation Registry.

BACKGROUND AND PURPOSE: There is controversy on the relationship of the type of atrial fibrillation (AF) to stroke. Although several studies show that patients with paroxysmal AF (PAF) have a stroke risk similar to those with persistent or permanent AF, recent studies suggest that PAF is associated with a lower rate of stroke. Limited data on stroke risk associated with PAF are evident in Asian populations. METHODS: The Registry Study of Atrial Fibrillation Patients in Fushimi-ku (Fushimi AF Registry) is a community-based survey of patients with AF in Fushimi-ku, Kyoto, Japan. Patients were categorized into 2 types of AF: PAF or sustained (persistent or permanent) AF. We compared clinical events between PAF (n=1588) and sustained AF (n=1716). RESULTS: Patients with PAF were younger, had less comorbidities, and received oral anticoagulants (OAC) less commonly. A lower risk of stroke/systemic embolism during follow-up period in the patients with PAF was consistently observed (non-OAC users: hazard ratio, 0.45; 95% confidence intervals, 0.27-0.75; P<0.01 and OAC users: hazard ratio, 0.59; 95% confidence interval, 0.35-0.93; P=0.03). The composite end point of stroke/systemic embolism/all-cause mortality was also lower in PAF, whether among OAC users (hazard ratio, 0.77; 95% confidence interval, 0.59-0.99; P=0.046) or non-OAC users (hazard ratio, 0.59; 95% confidence interval, 0.46-0.75; P<0.01). On multivariate analysis, PAF was an independent predictor of lower stroke/systemic embolism risk. CONCLUSIONS: In this large cohort of Japanese patients with AF, PAF was independently associated with lower incidence of stroke/systemic embolism than sustained AF. This may aid decision making for anticoagulation, especially in those patients with AF with few stroke risk factors. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834.