Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Japanese Patients With Venous Thromboembolism　- The Primary Results From the KUROSIO Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulation therapy in the acute phase of venous thromboembolism (VTE). However, there is limited real-world data for Japanese VTE patients.Methods and Results: The KUROSIO study (UMIN000023747) was a prospective long-term observational study comprising 1,017 patients with concurrent acute symptomatic pulmonary thromboembolism and proximal deep vein thrombosis (DVT) or isolated calf DVT initially treated with DOACs. After excluding 24 patients, 993 (mean age, 66.3±15.1 years; 58.6% females) were analyzed. The incidences of recurrent symptomatic VTE and major bleeding for up to 52 weeks after diagnosis were 3.2% and 2.2%, respectively. Multivariate analyses revealed chemotherapy and anemia as significant risk factors associated with recurrent symptomatic VTE and major bleeding, respectively. CONCLUSIONS: The efficacy and safety of DOACs in Japanese patients with VTE were determined in this real-world observational study.

Association of D-dimer level with thrombotic events, bleeding, and mortality in Japanese patients with solid tumors: a Cancer-VTE Registry subanalysis.

BACKGROUND: The D-dimer test is a simple test frequently used in routine clinical screening for venous thromboembolism (VTE). The Cancer-VTE Registry was a large-scale, multicenter, prospective, observational study in Japanese patients with cancer. This study aimed to clarify the relationship between D-dimer level at cancer diagnosis (baseline) and the incidence of events during cancer treatment (1-year follow-up period). METHODS: This was a post hoc sub-analysis of patients from the Cancer-VTE Registry whose D-dimer levels were measured at baseline. The incidence of events during the 1-year follow-up period was evaluated stratified by baseline D-dimer level. Adjusted hazard ratios for D-dimer level and events during the follow-up period were evaluated. RESULTS: Among the total enrolled patients, baseline D-dimer level was measured in 9020 patients. The mean ± standard deviation baseline D-dimer level was 1.57 ± 3.94 µg/mL. During the follow-up period, the incidence of VTE, cerebral infarction/transient ischemic attack (TIA)/systemic embolic events (SEE), bleeding, and all-cause death increased with increasing baseline D-dimer level. The incidence of all-cause death increased with increasing D-dimer level regardless of cancer stage. The adjusted hazard ratio of all-cause death was 1.03 (95% confidence interval: 1.02-1.03) per 1.0-µg/mL increase in baseline D-dimer level. CONCLUSIONS: Increases in D-dimer levels were associated with a higher risk of thrombotic events, such as VTE and cerebral infarction/TIA/SEE, during cancer treatment. Furthermore, higher D-dimer levels at cancer diagnosis were associated with a higher mortality rate, regardless of cancer stage.

Efficacy and Safety of Warfarin for the Treatment of Venous Thromboembolism　- A Multicenter Prospective Observational Cohort Study in Japan (AKAFUJI Study).

BACKGROUND: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE.Methods and Results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5-2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer. CONCLUSIONS: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Prognostication of Patients with Pulmonary Thromboembolism with and without Residual Deep Vein Thrombosis: A Subanalysis of the J'xactly Study.

Objectives: It is unclear whether patients with acute pulmonary thromboembolism (PE) with and without residual deep vein thrombosis (DVT) have different prognoses, and there is debate over whether inferior vena cava filters (IVCFs) should be used in conjunction with oral anticoagulants in patients with venous thromboembolism (VTE). Materials and Methods: The J'xactly involved 1,016 patients and was a multicenter, prospective, observational research. In this subanalysis, 419 patients with PE with or without residual DVT who received rivaroxaban with or without IVCFs between February 2016 and April 2018 in Japan were examined. Results: Of 419 patients with PE, 320 had residual DVT. There was no difference between the groups with and without DVT in terms of the percentage of patients who experienced symptomatic PE recurrence (2.8% [9/320] vs. 3.0% [3/99]) or who died from VTE-related complications (0.9% [3/320] vs. 1.0% [1/99]). The percentages of patients with symptomatic PE recurrence were 0% and 3.2%, and the percentages of patients who died from VTE-related causes were 0% and 1.1%, respectively, in the groups with (n=39) and without (n=281) IVCF, albeit not being statistically different. Conclusion: Patients with PE with and without residual DVT did not have a different incidence of symptomatic PE recurrence. These results require additional study to be confirmed.

Rivaroxaban treatment for asymptomatic venous thromboembolism: insights from the J'xactly study.

BACKGROUND: An established treatment strategy for asymptomatic pulmonary embolism (PE) or deep vein thrombosis (DVT) remains uncertain in Japan; therefore, in this study, we clarify the characteristics and outcomes of symptomatic compared to asymptomatic patients with PE or DVT. METHODS: This prospective, multicenter sub-analysis of the J'xactly study in Japan included 1,016 patients (mean age, 68; 41% male) with venous thromboembolism (VTE) treated with rivaroxaban. RESULTS: Asymptomatic PE patients (47% of PE patients) were more likely to have active cancer and asymptomatic proximal DVT at lower severity than symptomatic PE patients, despite no differences in age, sex, or the proportion receiving intensive 30 mg/day-rivaroxaban. Patients with asymptomatic DVT (34% of DVT patients) were older, had higher rates of female sex, active cancer, and distal DVT, and received shorter, less intense rivaroxaban treatment. Incidences did not differ between asymptomatic and symptomatic PE patients for recurrent symptomatic VTE (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.22-1.62; P = 0.31) or major bleeding (HR, 0.68; 95% CI, 0.20-2.33; P = 0.58), nor between asymptomatic and symptomatic DVT patients for recurrent symptomatic VTE (HR, 0.56; 95% CI, 0.23-1.40; P = 0.21) and major bleeding (HR, 1.47; 95% CI, 0.54-3.97; P = 0.45). CONCLUSIONS: The real-world composite adverse event rate for treatment with rivaroxaban, as physician-adjusted for dose and duration, was similar for asymptomatic and symptomatic patients regardless of the presence of PE or DVT, suggesting a favorable safety profile for potential rivaroxaban treatment for asymptomatic VTE.

Safety Profile and Effectiveness of Rivaroxaban for Patients With Venous Thromboembolism in Japan　- Results From Post-Marketing Surveillance (XASSENT).

BACKGROUND: The incidence of venous thromboembolism (VTE; pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) in Japan is increasing, but relatively small numbers of patients from Japan have been included in studies investigating rivaroxaban (a direct factor Xa inhibitor) for the treatment of VTE and preventing its recurrence.Methods and Results: An open-label, prospective, observational study (XASSENT [NCT02558465]) investigated the safety profile and effectiveness of rivaroxaban for ≤2 years in the treatment of VTE and prevention of its recurrence in Japanese clinical practice. Primary outcomes were major bleeding and symptomatic recurrent VTE. Statistical analyses were exploratory and descriptive. Overall, 2,540 patients were enrolled (safety analysis population [SAP], n=2,387; effectiveness analysis population [EAP], n=2,386). In the SAP, >80% of patients received the approved rivaroxaban dose, the mean (standard deviation) age was 66.6 (15.0) years, ≈74% were >50 kg, and 43% had a creatinine clearance ≥80 mL/min. PE+DVT, PE only, and DVT only were reported in 42%, 8%, and 50% of patients, respectively, and active cancer in 17% of patients. Major bleeding was reported in 69 patients (2.89%; 3.60%/patient-year; SAP) and symptomatic PE/DVT recurrence in 26 patients (1.09%; 1.36%/patient-year; EAP) during the treatment period. CONCLUSIONS: XASSENT provided information on the expected proportions of bleeding and VTE recurrence during rivaroxaban treatment in Japanese clinical practice; no new concerns of safety or effectiveness were found.

Duration of Initial Intensive Rivaroxaban Therapy for Patients With Venous Thromboembolism　- Subanalysis of the J'xactly Study.

Background: Rivaroxaban, a direct oral anticoagulant, is used as a first-line treatment to prevent venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). However, whether 21 days is optimal for the initial treatment duration has not been investigated. Methods and Results: In this subanalysis of the prospective multicenter observational J'xactly study, which included 1,039 Japanese patients with acute symptomatic/asymptomatic DVT/PE who were prescribed rivaroxaban, the VTE recurrence rate and incidence of bleeding complications were assessed in 667 patients who underwent intensive rivaroxaban treatment (15 mg, twice daily) for a short (1-8 days), intermediate (9-16), or standard (17-24) duration. The short treatment duration group showed a tendency for increased VTE recurrence/aggravation compared with the standard treatment duration group (6.10% vs. 2.60% per patient-year). The intermediate treatment duration group showed a higher incidence of bleeding events than the standard treatment duration group (9.34% vs. 2.16% per patient-year), without major differences in patient characteristics between the groups. Conclusions: In this subanalysis of the real-world observational J'xactly study of VTE treatment and prevention in Japanese patients with acute symptomatic/asymptomatic DVT/PE, the standard initial intensive rivaroxaban treatment duration (17-24 days) appeared to be safe and effective, providing important insights into the clinical outcomes of the initial rivaroxaban treatment duration in this population.

Relationship between baseline D-dimer and prognosis in Japanese patients with venous thromboembolism: Insights from the J'xactly study.

Background: D-dimer is a biomarker of fibrin production and degradation, and changes in D-dimer concentration suggest fibrin clot formation, which is associated with thromboembolism and hypercoagulable states. Thus, an elevated D-dimer concentration could be a useful prognostic predictor for patients with venous thromboembolism (VTE). Methods and results: In this subanalysis of the J'xactly study, a prospective multicenter study conducted in Japan, we examined the clinical outcomes of 949 patients with VTE stratified by baseline D-dimer concentration. The median D-dimer concentration was 7.6 µg/ml (low D-dimer group: <7.6 µg/ml [n = 473, 49.8%]; high D-dimer group: ≥7.6 µg/ml [n = 476, 50.2%]). The mean age of the patients was 68 years, and 386 patients (40.7%) were male. Compared with the low D-dimer group, the high D-dimer group had more frequent pulmonary embolism with or without deep vein thrombosis (DVT), proximal DVT, atrial fibrillation, or diabetes mellitus, and underwent intensive treatment with 30 mg/day rivaroxaban. The incidence of composite clinically relevant events (recurrence or exacerbation of symptomatic VTE, acute coronary syndrome [ACS], ischemic stroke, death from any cause, or major bleeding) was higher in the high D-dimer group than in the low D-dimer group (11.1% vs. 7.5% per patient-year; hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; p = 0.025). There was no significant difference between the high and low D-dimer groups in the incidence of VTE (2.8% vs. 2.5% per patient-year, respectively; p = 0.788), ACS (0.4% per patient-year vs. not observed, respectively; p = 0.078), or major bleeding (4.0% vs. 2.1% per patient-year, respectively; p = 0.087), but there was a significant difference in the incidence of ischemic stroke (1.0% per patient-year vs. not observed, respectively; p = 0.004). Conclusion: Elevated D-dimer concentration may be an important prognostic predictor in Japanese patients with VTE.Clinical Trial Registration: UMIN CTR, UMIN000025072 (https://www.umin.ac.jp/ctr/index.htm).

Effectiveness and safety of rivaroxaban in patients with venous thromboembolism and active cancer: A subanalysis of the J'xactly study.

BACKGROUND: Data on the effectiveness and safety of rivaroxaban for the treatment of patients with venous thromboembolism (VTE) and active cancer are limited in the Japanese real-world setting. METHODS: In this subanalysis of the J'xactly study, which was a multicenter, prospective, observational study, we evaluated the effectiveness and safety of rivaroxaban in patients with acute VTE and active cancer (n = 193) versus those without active cancer (n = 823). RESULTS: Compared with patients without active cancer, those with active cancer demonstrated a significantly different age distribution, with fewer aged <65 and ≥75 years; a lower proportion of women; a lower mean body mass index; and a lower proportion of physical inactivity, injury, thrombophilia, and heart failure. There was no difference in the initial dose distribution of rivaroxaban between patients with and without active cancer. The incidences of recurrence or aggravation of symptomatic VTE and major bleeding were not significantly different [VTE: 1.44 % vs. 2.80 % per patient-year, hazard ratio (HR) 0.50, 95 % confidence interval (CI) 0.18-1.39, p = 0.172; major bleeding: 4.49 % vs. 2.55 % per patient-year, HR 1.80, 95 % CI 0.82-3.95, p = 0.137]. Approximately 10 % of patients with active cancer died at 6 months, with a significantly higher cumulative all-cause mortality rate than those without active cancer (23.29 % vs. 2.03 % per patient-year, HR 11.31, 95 % CI 7.30-17.53, p < 0.001). CONCLUSIONS: In patients with VTE and active cancer, rivaroxaban showed acceptable effectiveness, although clinically significant bleeding remains a concern. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000025072.

Effectiveness and safety of the direct oral anticoagulant in acute distal deep vein thrombosis: From the prospective multicenter observational study, J'xactly, in Japan.

OBJECTIVES: We assessed the effectiveness and safety of rivaroxaban in patients with isolated distal deep vein thrombosis (IDDVT). METHODS: Symptomatic venous thromboembolism (VTE) and major bleeding were assessed. RESULTS: Of 1016 patients with acute symptomatic/asymptomatic DVT and/or pulmonary embolism treated with rivaroxaban, 288 had IDDVT and 294 had proximal DVT (pDVT). The IDDVT group had fewer patients on the higher rivaroxaban dose (30 mg/day) (42.7% vs. 66.0%) and a shorter treatment duration (135.5 vs 369.5 days) than the pDVT group. VTE recurrence occurred in 14 and 11 patients with IDDVT and pDVT, respectively (2.89% vs. 2.29% per patient-year; p = 0.534). Major bleeding was less frequent in the IDDVT group (1.55% vs. 4.53% per patient-year; p = 0.044). Comparable effectiveness and safety were observed with 15 and 30 mg/day rivaroxaban in the IDDVT group. CONCLUSIONS: Short-term, low-dose rivaroxaban seems safe and effective for IDDVT treatment.

Rivaroxaban Treatment for Patients With Unprovoked or Provoked Venous Thromboembolism　- Subanalysis of the J'xactly Study.

Background: The efficacy and safety of direct oral anticoagulants (DOACs) in patients with unprovoked venous thromboembolism (VTE) remain unclear. Methods and Results: In this subanalysis of the J'xactly study, a multicenter prospective observational study, we evaluated the safety and effectiveness of rivaroxaban in patients with acute VTE according to unprovoked (n=388) or provoked (n=557) VTE status. Median follow-up was 21.2 months. Compared with patients in the provoked group, patients in the unprovoked group were younger, less likely to be female, and had higher body weight. The incidence of symptomatic VTE recurrence was significantly higher in the unprovoked than provoked VTE group (3.54% vs. 1.77% per patient-year; P=0.032). There was no significant difference in the incidence of major bleeding events between rivaroxaban-treated patients with unprovoked and provoked VTE (2.31% vs. 3.75% per patient-year; P=0.289). Although the proportion of patients with a body mass index (BMI) ≥25 kg/m2 who were non-users of antiplatelet agents was higher in the unprovoked VTE group, there was no interaction effect (BMI: 4.58% vs. 1.55% per patient-year [P=0.040; P for interaction=0.361]; concomitant antiplatelet agent non-users: 3.65% vs. 1.72% per patient-year [P=0.028; P for interaction=0.627]). Conclusions: This subanalysis suggests the safety and effectiveness of rivaroxaban in patients with unprovoked VTE. In such patients, DOAC discontinuation should be considered carefully, particularly in those not using antiplatelet agents and those with a high BMI.

Clinical Outcome After Discontinuation of Anticoagulation Therapy in Japanese Patients With Venous Thromboembolism　- Insights From the J'xactly Study.

Background: Rivaroxaban, a direct oral anticoagulant, is used as first-line treatment to prevent venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). However, the frequency of rivaroxaban discontinuation and the subsequent clinical outcomes remain unclear. Methods and Results: The study was a subanalysis of the prospective, multicenter, observational J'xactly study, conducted in Japan, and included patients who underwent anticoagulant discontinuation without major bleeding and recurrent VTE. The modified intention-to-treat population (n=1,016) included 579 patients (57%) who underwent anticoagulant discontinuation during a mean follow-up period of 20.2 months (mean [±SD] anticoagulation period 6.9±6.2 months). Patients were divided into 3 groups: those with active cancer, those without active cancer and a transient risk factor for VTE, and those without active cancer or a transient risk factor and/or with previous VTE (unprovoked group). After discontinuation, VTE recurrence occurred in 4.1% of patients, with an annual incidence of 4.6%/year and an increased tendency in the unprovoked group; major bleeding occurred in 8 patients (1.4%; annual incidence 1.1%/year), of whom half were in the cancer group. Conclusions: This analysis of a real-world observational study provides data on VTE recurrence after rivaroxaban discontinuation, which will facilitate anticoagulant discontinuation according to individual risk-benefit considerations.

Impact of hyperuricemia on coronary blood flow and in-hospital mortality in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Although serum uric acid (UA) is considered as a risk factor for cardiovascular disease, few data exist regarding the relationship between hyperuricemia, coronary blood flow, and subsequent outcome in patients with acute myocardial infarction (AMI). The purpose of our study is to assess whether hyperuricemia is associated with suboptimal coronary flow and increased risk of mortality in patients with AMI after percutaneous coronary intervention (PCI). METHODS: Using the Rural AMI registry data, 989 consecutive patients with AMI who underwent emergent PCI and had UA measurement at admission were analyzed. We defined hyperuricemia as serum UA ≥7.0 mg/dL in men and ≥ 6.0 mg/dL in women. The primary endpoint was suboptimal coronary flow, defined as post PCI Thrombosis In Myocardial Infarction flow grade ≤ 2. The secondary outcome was in-hospital mortality. RESULTS: Hyperuricemia was found in 249 (25.2%) patients. Patients with hyperuricemia were more often complicated with cardiogenic shock compared with those without (16.9% vs. 7.4%, p < 0.001). In addition, the median high-sensitivity C-reactive protein was significantly higher in patients with hyperuricemia (0.18 mg/dL; IQR, 0.09-0.71 mg/dL) than in those without (0.14 mg/dL; IQR, 0.07-0.41 mg/dL, p < 0.05). Under these conditions, the prevalence of suboptimal coronary flow after PCI (17.3% vs. 10.1%, p < 0.05) and in-hospital mortality (10.8% vs. 3.6%, p < 0.001) were significantly higher in patients with hyperuricemia compared with those without. Multivariable logistic regression analysis revealed that hyperuricemia was significantly associated with suboptimal coronary flow [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.49; p < 0.05] and in-hospital mortality (OR, 2.08; 95% CI, 1.05-4.12; p < 0.05). CONCLUSIONS: Assessment of serum UA upon admission provides useful information for predicting suboptimal coronary flow and in-hospital mortality in patients with AMI undergoing PCI.

Characteristics and clinical outcomes of Japanese patients with venous thromboembolism receiving under-dose rivaroxaban: subanalysis of J'xactly.

OBJECTIVE: Rivaroxaban is commonly prescribed to prevent venous thromboembolism (VTE). Although lower than standard dosages (under-dosing) may be administered in the real-world setting, data on subsequent clinical outcomes in Japanese patients are lacking. METHODS: The prospective, multicenter, observational J'xactly study enrolled patients with acute symptomatic/asymptomatic deep vein thromboses (DVT), pulmonary embolism (PE), or both, who were prescribed rivaroxaban. This subanalysis investigated patient characteristics and outcomes associated with rivaroxaban under-dosing. RESULTS: Among 1016 evaluable patients, 667 (65.6%) received an initial standard dosage of rivaroxaban (30 mg/day) and 349 (34.4%) received an initial under-dosage (20 mg/day, n = 22; 15 mg/day, n = 282; and 10 mg/day, n = 45). Those receiving an under-dose had significantly lower body weight and slower pulse rate compared with the standard-dose group regardless of DVT or PE status. Under-dosing was common for distal DVTs, but less frequent for massive/submassive PEs. There were no differences between under-dose and standard-dose groups in the incidences of recurring symptomatic VTEs (DVT: 1.77% vs. 3.35% per patient-year, p = .138; PE: 0.84% vs. 2.84% per patient-year, p = .208) or major bleeding (DVT: 3.55% vs. 3.41% per patient-year, p = .960; PE: not observed vs. 2.83% per patient-year, p = .132). CONCLUSIONS: In the real-world setting, rivaroxaban under-dosing for patients with VTE occurred in those with lower body weight, slower pulse rate, distal DVT, or non-massive PEs. There were no statistically significant differences in the clinical outcomes for patients received under-dose of rivaroxaban at the discretion of the physicians in the clinical practice compared with those received standard dose of rivaroxaban.

One-year incidence of venous thromboembolism, bleeding, and death in patients with solid tumors newly initiating cancer treatment: Results from the Cancer-VTE Registry.

INTRODUCTION: Although many publications have reported the incidence of venous thromboembolism (VTE) in patients with cancer from Western countries, to date, no prospective East Asian studies have been published, and potential racial differences remain unclear. The multicenter, prospective, observational Cancer-VTE Registry aimed to clarify the incidence of VTE and bleeding and identify risk factors in Japanese patients with solid tumors after one year of follow-up. MATERIALS AND METHODS: Patients with colorectal, lung, stomach, pancreatic, breast, or gynecologic cancer were enrolled after VTE screening and before starting cancer treatment. The follow-up period was one year. The main outcomes were the incidences of symptomatic VTE, bleeding events (major or clinically relevant non-major), and all-cause death, evaluated according to VTE presence/absence at baseline. Multivariate analyses were conducted to identify risk factors for events. RESULTS: Among 9630 patients, the one-year cumulative incidences of symptomatic VTE, bleeding events, and all-cause death were 0.5%, 1.4%, and 12.2%, respectively. The majority of VTEs identified at baseline were asymptomatic distal deep vein thromboses; however, affected patients had higher event rates during the follow-up period. The most important independent risk factor for developing symptomatic VTE, bleeding events, and death during the follow-up period was the presence of symptomatic or asymptomatic VTE at baseline. CONCLUSIONS: These data have revealed the incidence of symptomatic VTE in Japanese patients with solid tumors during one year of follow-up. The presence of any VTE before initiating cancer treatment was an independent risk factor for symptomatic VTE, bleeding events, and death during subsequent treatment.

Real-World Insurance Claims Analysis of Venous Thromboembolism in Japanese Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD), which encompasses both ulcerative colitis (UC) and Crohn's disease (CD), is a risk factor for venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). AIM: To investigate the incidence of, and risk factors for, VTE in patients with IBD in Japan. METHODS: This was a retrospective, non-interventional study in patients with IBD from the Japan Medical Data Center claims database. Incidence rates (IRs; unique patients with events per 100 patient-years) were calculated for VTE, DVT, and PE among the IBD, UC, and CD cohorts. Odds ratios of potential risk factors were calculated by univariate and multivariate analyses in a nested case-control design. RESULTS: Overall, 16 273 patients with IBD were included: 13 585 with UC and 3443 with CD. VTE events occurred in 1.3%, 1.2%, and 1.9% of patients with IBD, UC, and CD, respectively. In patients with IBD, UC, and CD, IRs of VTE were 0.45, 0.40, and 0.64, respectively, IRs of DVT were 0.42, 0.38, and 0.61, respectively, and IRs of PE were 0.07, 0.07, and 0.11, respectively. In patients with IBD, treatment history (immunomodulators), cardiovascular risk (hypertension, high-density lipoprotein or diabetes mellitus, and history of coronary artery disease or heart failure), malignancy, and undergoing major surgery were identified as potential risk factors for VTE in the multivariate analysis, with similar risk factors reported for patients with UC and CD. CONCLUSIONS: This large study provides insight into the incidence and risk factors for VTE in patients with IBD from Japan.

Clinical Implication of the Right Ventricular/Left Ventricular Diameter Ratio in Patients with Pulmonary Thromboembolism.

The role of the right to left ventricular (RV/LV) diameter ratio in predicating long-term outcomes in patients with pulmonary thromboembolisms (PTEs) treated with direct oral anticoagulants is unclear.We investigated the association between the RV/LV diameter ratio and clinical outcomes in PTE patients under rivaroxaban from the data of a multicenter, prospective, observational study (J'xactly Study) in Japanese patients with acute venous thromboembolisms (VTEs) including deep vein thromboses, PTEs, or both. Of a total of 1,039 patients with an acute VTE (from December 2016 to April 2018), 429 were diagnosed with PTEs, however, the population in this study consists of 216 patients in whom the RV/LV diameter ratio measured on the axial CT or transthoracic echocardiogram was available.The RV/LV diameter ratio increased significantly with the severity of the PTE classification (nonmassive 0.79 [0.67-0.93], submassive 1.10 [0.83-1.31], massive 1.13 [0.94-1.19], arrest or collapse 1.38 [0.66-2.38], P < 0.001). During a median follow-up of 624 (550-690) days, a sum of the composite adverse events including recurrent VTEs, acute coronary syndrome, ischemic strokes, death from any cause, or major bleeding events occurred in 26 patients (12.0%, 7.58 events per 100 patient-years). Multivariate analysis revealed that an RV/LV diameter ratio ≥ 1.0 had no association with the incidence of composite adverse events (HR 1.34, 95% confidence interval 0.59-2.91, P = 0.48).In summary, in Japanese PTE patients under rivaroxaban, the RV/LV diameter ratio measured on the CT or transthoracic echocardiogram was associated with the PTE severity, but not with the clinical outcomes.

Design and Baseline Data for a Prospective Observational Study of Rivaroxaban in Patients with Venous Thromboembolism in Japan (XASSENT).

Background The efficacy and safety of rivaroxaban have been demonstrated in phase 3 trials of patients with venous thromboembolism (VTE; pulmonary embolism [PE] and deep vein thrombosis [DVT]). Data regarding rivaroxaban treatment of VTE in routine Japanese clinical practice remain limited. Objectives XASSENT will evaluate rivaroxaban treatment of VTE in real-world Japanese clinical practice. We report the study design and baseline patient characteristics. Methods XASSENT (NCT02558465) is an open-label, prospective observational, post-marketing surveillance cohort study in patients receiving rivaroxaban treatment for VTE. Enrolment took place between November 2015 and March 2018. XASSENT will follow patients for up to 2 years. Primary outcome variables: major bleeding and symptomatic recurrent VTE. Statistical analyses are exploratory and descriptive. Results Baseline patient characteristics at June 2020 ( n = 2,299) are presented (58.2% female; mean age 66.7 years; mean weight 60.9 kg). The population encompasses patients with wide-ranging characteristics including older age, low weight, and renal dysfunction. Most participants (67.6%) had a history of VTE risk factors at baseline. Half of the population (50.4%) had DVT only; 41.4% had DVT with PE; 8.2% had PE only. Overall, 68.4% were inpatients and 77.1% had symptomatic VTE. Rivaroxaban was prescribed for initial treatment in 84.6% of patients and maintenance treatment in 15.4%. Most were prescribed the approved dose of rivaroxaban for initial (30 mg daily; 84.4%) or maintenance (15 mg daily; 81.9%) treatment of VTE in Japan. The most common reason for selecting non-recommended dose was 'elderly'. Conclusions Results from XASSENT will complement phase 3 trial data and inform clinical practice.

Safety and Effectiveness of Apixaban in Japanese Patients With Venous Thromboembolism in Clinical Practice　- A Post-Marketing Surveillance.

BACKGROUND: A post-marketing surveillance study (STANDARD-VTE) evaluated the real-world safety and effectiveness of apixaban in Japanese patients prescribed for either the treatment of venous thromboembolism (VTE) or prevention of recurrent VTE.Methods and Results:Patients newly initiated on apixaban were followed up for 52 weeks or 28 days post-discontinuation. Subgroup analysis was performed on patients with and without active cancer, and on patients with provoked VTE and with unprovoked VTE. A total of 1,119 patients were enrolled. Of these, 43.1% were aged ≥75 years, 46.4% had body weight ≤60 kg, and 21.3% had active cancer; mean serum creatinine was 0.76 mg/dL. The incidence of adverse drug reactions (ADRs) was 8.85%, and that of severe ADRs was 3.22%. Incidence of any bleeding, major bleeding, and recurrent VTE was 6.70%, 3.40%, and 0.80%, respectively. In patients starting apixaban 10 mg twice daily, THE incidence of any bleeding and major bleeding was 7.72% and 3.86%, respectively. In patients with active cancer, THE incidence of any bleeding and major bleeding was 16.81% and 9.24%, respectively. CONCLUSIONS: No new safety signals of apixaban were identified in Japanese patients with VTE. In this study, the safety and effectiveness of apixaban in real-world practice was consistent with the results of the apixaban phase III trial.