COMMAND Venous Thromboembolism Registry Research Articles

Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism

BackgroundThe duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding. ObjectivesAnalyze rates and case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation. MethodsWe compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding. ResultsOf 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio [HR], 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding. ConclusionRecurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these outcomes.

Application of the RIETE score to identify low-risk patients with pulmonary embolism: From the COMMAND VTE Registry

BackgroundThe RIETE score could be specifically useful for identification of low-risk pulmonary embolism (PE) patients for home treatment. However, the external validation of the RIETE score has been limited. MethodsThe COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). The current study population consisted of 1479 patients with acute PE, who were divided into 2 groups; RIETE scores of 0 (N = 260) and ≥ 1 (N = 1219). ResultsThe cumulative 10-day and 30-day incidences of a composite endpoint of all-cause death, recurrent PE, or major bleeding were lower in patients with the RIETE score of 0 than in those with the RIETE score of ≥1 (10-day: 0.4 % vs. 6.7 %, P < 0.001, and 30-day: 0.4 % vs. 10.0 %, P < 0.001). The area under the receiver-operating characteristic curve (AUC) in the RIETE score for the 10-day composite endpoint showed numerically better predictive ability than that in the sPESI score (0.77 vs. 0.73, P = 0.07), and the AUC in the RIETE score for the 30-day composite endpoint showed significantly better predictive ability than that in the sPESI score (0.77 vs. 0.71, P = 0.003). ConclusionsThe RIETE score was well validated in the current large real-world registry. The RIETE score of 0 could identify patients with reasonably low risks of the 10-day and 30-day composite endpoint of all-cause death, recurrent PE, or major bleeding.

Age and long-term outcomes of patients with venous thromboembolism: From the COMMAND VTE Registry

BackgroundThere is still a scarcity of data on the relation between age and long-term clinical outcomes of patients with venous thromboembolism (VTE). MethodsThe COMMAND VTE Registry was a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We divided the entire cohort into 3 groups: patients aged <65 years (N = 1100, 36.7%), patients aged 65 ≤ and ≤ 80 years (N = 1314, 43.4%), and patients aged >80 years (N = 603, 19.9%). ResultsDiscontinuation of anticoagulation therapy during the follow-up period was most frequent in patients aged <65 years (44%, 38% and 33%, P < 0.001). The cumulative 5-year incidences were 12.7%, 9.8% and 7.4% for recurrent VTE, 10.8%, 12.2% and 14.9% for major bleeding, and 23.0%, 31.4%, and 38.6% for all-cause death. Adjusting for cofounders and taking into account the competing risk of all-cause death, the lower risk of patients aged >80 years, and those aged 65 ≤ and ≤ 80 years relative to those aged <65 years remained significant for recurrent VTE (65 ≤ age ≤ 80 years, HR: 0.71, 95%CI: 0.53–0.94, P = 0.02; age > 80 years, HR: 0.59, 95%CI: 0.39–0.89, P = 0.01), and the risk remained insignificant for major bleeding (65 ≤ age ≤ 80 years, HR: 1.00, 95%CI: 0.76–1.31, P = 0.98; age > 80 years, HR: 1.17, 95%CI: 0.83–1.65, P = 0.37). ConclusionsIn the current real-world VTE registry, there was no significant difference in the risk of major bleeding depending on different age groups, while younger patients showed an excess risk for recurrent VTE compared with older patients.

Validity of Using Japanese Administrative Data to Identify Inpatients With Acute Pulmonary Embolism: Referencing the COMMAND VTE Registry.

Acute pulmonary embolism (PE) is a life-threatening in-hospital complication. Recently, several studies have reported the clinical characteristics of PE among Japanese patients using the diagnostic procedure combination (DPC)/per diem payment system database. However, the validity of PE identification algorithms for Japanese administrative data is not yet clear. The purpose of this study was to evaluate the validity of using DPC data to identify acute PE inpatients. The reference standard was symptomatic/asymptomatic PE patients included in the COntemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) registry, which is a cohort study of acute symptomatic venous thromboembolism (VTE) patients in Japan. The validation cohort included all patients discharged from the six hospitals included in both the registry and DPC database. The identification algorithms comprised diagnosis, anticoagulation therapy, thrombolysis therapy, and inferior vena cava filter placement. Each algorithm's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated. A total of 43.4% of the validation cohort was female, with a mean age of 67.3 years. The diagnosis-based algorithm showed a sensitivity of 90.2% (222/246; 95% confidence interval [CI], 85.8-93.6%), a specificity of 99.8% (228,485/229,027; 95% CI, 99.7-99.8%), a PPV of 29.1% (222/764; 95% CI, 25.9-32.4%) and an NPV of 99.9% (228,485/229,509; 95% CI, 99.9-99.9%) for identifying symptomatic/asymptomatic PE. Additionally, 94.6% (159/168; 95% CI, 90.1-97.5%) of symptomatic PE patients were identified using the diagnosis-based algorithm. The diagnosis-based algorithm may be a relatively sensitive method for identifying acute PE inpatients in the Japanese DPC database.

Causes of long-term mortality in patients with venous thromboembolism in the real world: From the COMMAND VTE registry

IntroductionThere is still a scarcity of data on causes of long-term mortality in patients with venous thromboembolism (VTE). Materials and methodsThe COMMAND VTE Registry is a physician-initiated, retrospective, multicenter cohort study in which consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan were included between January 2010 and August 2014. We investigated detailed causes and risk factors for long-term mortality. ResultsDuring a median observation period of 1218 days, a total of 764 patients died, and the prevalence of active cancer was higher in patients who died than in patients alive (61 % versus 10 %, P < 0.001). The cumulative incidences of cardiac death, pulmonary embolism (PE)-related death, bleeding death, cancer death, and non-cardiovascular non-cancer death were 2.2 %, 2.9 %, 2.0 %, 16.1 %, and 6.7 % at 5 years, respectively. The incidence of cancer death increased gradually, which was the most common cause of long-term death. Among patients without active cancer, the incidence of PE-related death increased rapidly and became a plateau beyond the acute phase, whereas the incidence of non-cardiovascular non-cancer death kept increasing, which became most common in the long term. The separate multivariable analysis among patient with and without active cancer identified independent risk factors of all-cause death including a few patient characteristics among patients with active cancer and several patient characteristics among patients without active cancer. ConclusionsCancer was the most common cause of long-term mortality, while non-cardiovascular non-cancer death became most common among patients without active cancer.

Optimal quality of vitamin K antagonist therapy in Japanese patients with venous thromboembolism

BackgroundVitamin K antagonist (VKA) remains an essential option for venous thromboembolism (VTE), although direct oral anticoagulants have become available. However, there is a paucity of data on the optimal intensity and quality of control for VKA in Japanese. MethodsThe COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1938 patients who received VKA with prothrombin time-international normalized ratio (PT-INR) measurement >5 times. The primary outcome measure was a composite of symptomatic VTE recurrence or major bleeding at 1 year. The presumed optimal quality of VKA therapy was defined as the combination of PT-INR range and time in therapeutic range (TTR) with the numerically lowest event rate. ResultsThe group with TTR ≥70 % based on PT-INR range ≥1.5 and <2.0 showed the lowest cumulative incidence rate. The cumulative 1-year incidence and the adjusted risk for the primary outcome measure were significantly lower in the optimal quality group than in the non-optimal quality group (5.2 % vs. 11.7 %, p = 0.001, and HR 0.49, 95%CI 0.28–0.81). Similarly, the cumulative 1-year incidences of a recurrent VTE, major bleeding, and all-cause death were significantly lower in the optimal quality group (recurrent VTE: 2.5 % vs. 6.0 %, p = 0.02; major bleeding: 2.8 % vs. 7.0 %, p = 0.008; and all-cause death: 2.8 % vs. 12.6 %, p < 0.0001). The lower risk of the optimal quality group relative to non-optimal quality group for the clinical outcomes was consistent regardless of the etiology of VTE (active cancer, transient risk factor, and unprovoked). ConclusionsThe current VTE registry showed the optimal intensity of VKA therapy was target PT-INR range ≥1.5 and <2.0, which could support the current Japanese guideline recommendation, and the good quality of control for VKA therapy of TTR ≥70 % was independently associated with better outcomes.

Anticoagulation strategies and clinical outcomes after bleeding events during anticoagulation therapy for venous thromboembolism in the practice-based Japanese registry.

There is a paucity of data on anticoagulation strategies and clinical outcomes after bleeding events for venous thromboembolism (VTE). In a multicenter Japanese registry enrolling 3027 patients with acute symptomatic VTE, after excluding 430 patients with thrombolysis and 207 patients without anticoagulation therapy, the current study population consisted of 2390 patients, who were divided into patients with major bleeding, clinically relevant non-major (CRNM) bleeding and no bleeding during anticoagulation therapy. All-cause death at 90days after the bleeding events was evaluated as the primary outcome. There were 189 patients with major bleeding, 147 patients with CRNM bleeding, and 2054 patients without bleeding. Among 189 patients with major bleeding, 142 patients (75%) discontinued anticoagulants, of whom patients with temporary discontinuation and those with permanent discontinuation accounted for 63 patients (44%) and 79 patients (56%), and 58 patients (30.7%) died within 90days after the bleeding events. The multivariable logistic regression model among patients with bleeding events revealed that active cancer and bleeding events within 90days after VTE diagnosis were independently associated with 90-day mortality after the bleeding events (active cancer: OR 5.05, 95%CI 2.82-9.05; bleeding events within 90days after VTE diagnosis: OR 2.23, 95%CI 1.25-3.96). In this practice-based large registry, anticoagulants were frequently discontinued in patients who experienced major bleeding events during anticoagulation therapy and nearly half of them restarted anticoagulants with mortality rate of approximately 30% within 90days after the bleeding events, and active cancer was the most prevalent cause of death.Clinical trial registration COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000021132.

Incidence, clinical characteristics and long-term prognosis of postoperative symptomatic venous thromboembolism: a retrospective cohort study

ObjectivesThe purpose of this study was to evaluate the incidence, clinical characteristics and prognosis of postoperative symptomatic venous thromboembolism (VTE) in Japan.DesignRetrospective observational study. Two data sets, Contemporary ManageMent AND...

Risk factors of recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism: from the COMMAND VTE Registry

Abstract Background/Introduction Patients with venous thromboembolism (VTE), including pulmonary embolism (PE), have a long-term risk of recurrence, and anticoagulation therapy is recommended for the prevention of recurrence. The latest 2019 European Society of Cardiology (ESC) guideline classified the risks of recurrence into low- (&amp;lt;3%/year), intermediate- (3–8%/year), and high- (&amp;gt;8%/year) risk, and recommended the extended anticoagulation therapy of indefinite duration for high-risk patients as well as intermediate-risk patients. However, extended anticoagulation therapy of indefinite duration for all of intermediate-risk patients have been a matter of active debate. Thus, additional risk assessment of recurrence in intermediate-risk patients might be clinically relevant in defining the optimal duration of anticoagulation therapy. Furthermore, bleeding risk during anticoagulation therapy should also be taken into consideration for optimal duration of anticoagulation therapy. However, there are limited data assessing the risk of recurrence as well as bleeding in patients with intermediate-risk for recurrence based on the classification in the latest 2019 ESC guideline. Purpose The current study aimed to identify the risk factors of recurrence as well as major bleeding in patients with intermediate-risk for recurrence, using a large observational database of VTE patients in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling 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. Results 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). Conclusions 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. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Risk factors of recurrence in patients with cancer-associated venous thromboembolism: from the COMMAND VTE Registry

Abstract Background/Introduction Cancer is a strong risk factor for the development of venous thromboembolism (VTE) including pulmonary embolism (PE) and deep vein thrombosis (DVT). Patients with VTE have a long-term risk of recurrence, which can be prevented by anticoagulation therapy. Prolonged anticoagulation therapy is recommended for patients with cancer-associated VTE, although the risk of recurrence might depend on the individual patient. Purpose We aimed to identify the risk factors of recurrence in patients with cancer-associated VTE. Methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTE among 29 Japanese centers between January 2010 and August 2014. The present study population consisted of 695 cancer-associated VTE patients. The primary outcome measure in the present study was recurrent VTE, which was defined as PE and/or DVT with symptoms accompanied by confirmation of a new thrombus or exacerbation of the thrombus by objective imaging examinations or autopsy. Discontinuation of anticoagulation was defined as a withdrawal of anticoagulation therapy lasting &amp;gt;14 days for any reason. We selected clinically relevant variables and variables with P values &amp;lt;0.1 in a univariate analysis as potential risk factors, and constructed a multivariable Cox proportional hazard model for recurrent VTE incorporating the anticoagulation therapy status as a time-updated covariate. Results Among the 695 study patients, recurrent VTE occurred in 78 patients, of whom 54 (69%) occurred within 6 months. The cumulative incidence of recurrent VTE was 7.7% at 3-months, 8.9% at 6-months, 11.8% at 1-year, and 17.7% at 5-years. The cumulative incidence of discontinuation of anticoagulation therapy was 18.0% at 3-months, 29.5% at 6-months, 43.4% at 1-year, and 66.5% at 5-years. The cumulative 5-year incidence of recurrent VTE was most frequent in patients with uterus/ovary cancer (26.0%), followed by those with lung cancer (24.7%). The multivariable Cox proportional hazard model revealed that chronic kidney disease (HR, 2.27; 95% CI, 1.36–3.77, P=0.002), a high D-dimer level at the time of VTE diagnosis (HR, 2.85; 95% CI, 1.71–4.74, P&amp;lt;0.001), advanced cancer (HR, 1.69; 95% CI, 1.05–2.72, P=0.03) and discontinuation of anticoagulation therapy (HR, 2.66; 95% CI, 1.53–4.63, P&amp;lt;0.001) were independently associated with an increased risk of recurrent VTE. No cancer site was independently associated with an increased risk for recurrent VTE when adjusting for the above mentioned risk factors in the multivariable Cox proportional hazard model, although the risk of recurrent VTE numerically differed according to the cancer site. Conclusions Among patients with cancer-associated VTE, chronic kidney disease, a high D-dimer level at the time of VTE diagnosis, advanced cancer, and discontinuation of anticoagulation therapy were independent risk factors of recurrence. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation Figure 1Figure 2

Severity of pulmonary embolism at initial diagnosis and long-term clinical outcomes: From the COMMAND VTE Registry

BackgroundThere is a paucity of data on the long-term clinical outcomes according to the severity of pulmonary embolism (PE) at initial diagnosis. MethodsThe COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE). After excluding 1312 patients without PE, the current study population consisted of 1715 patients with PE, who were divided into 3 groups according to the clinical severity; massive PE, sub-massive PE and low-risk PE. ResultsThere were 179 patients (10%) with massive PE, 742 patients (43%) with sub-massive PE, and 794 patients (46%) with low-risk PE. By the landmark analysis at 3 months, the cumulative incidences of recurrent VTE were similar among the 3 groups both within and beyond 3 months (Massive PE: 2.9%, Sub-massive PE: 4.2%, and Low-risk PE: 3.3%, P = 0.61, and 4.3%, 8.8%, and 7.8% at 5 years, P = 0.47, respectively). After adjusting confounders, the risk of massive PE relative to low-risk PE for recurrent VTE beyond 3 months remained insignificant (adjusted HR 0.54, 95% CI: 0.13–1.51, P = 0.27). Patients with massive PE at initial diagnosis more often presented as severe recurrent PE events than those with sub-massive and low-risk PE. ConclusionsIn the current real-world large registry, the long-term risk of overall recurrent VTE in patients with massive PE at initial diagnosis did not significantly differ from those with sub-massive and low-risk PE beyond 3 months, although patients with massive PE at initial diagnosis more frequently developed recurrent VTE as PE with severe clinical presentation.

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 ≥ 75years (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 .

Influence of low body weight on long-term clinical outcomes in patients with venous thromboembolism: From the COMMAND VTE registry

IntroductionThere is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE). Materials and methodsThe COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (>60 kg). ResultsPatients with lower body weight were older (70.8 versus 60.9 years, P < 0.001), and more often women (75% versus 38%, P < 0.001), and more often had active cancer (27% versus 19%, P < 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P < 0.001, and 35.8% versus 19.8%, P < 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16–2.12, P = 0.003, and HR 1.50, 95%CI: 1.24–1.81, P < 0.001, respectively). ConclusionsIn the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE.

Impact of no, distal, and proximal deep vein thrombosis on clinical outcomes in patients with acute pulmonary embolism: From the COMMAND VTE registry

BackgroundThe majority of acute pulmonary embolism (PE) is caused by thrombus developed from leg veins. However, impact of concomitant deep venous thrombosis (DVT) on clinical outcomes has not been fully evaluated in patients with acute PE. MethodsThe COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic venous thromboembolism (VTE) in Japan. The current study population consisted of 655 acute PE patients who underwent lower extremities ultrasound examination at diagnosis for the assessment of concomitant DVT status. ResultsThere were 424 patients with proximal DVT (64.7%), 162 patients with distal DVT (24.7%), and 69 patients with no DVT (10.5%). The cumulative 90-day incidence of all-cause death was higher in proximal DVT patients than in distal DVT and no DVT patients (7.9%, 2.5%, and 1.4%, p = 0.01). Regarding the causes of death, the cumulative 90-day incidence of PE-related death was low, and not significantly different across the 3 groups (1.4%, 0.6%, and 1.7%, p = 0.62). The most frequent cause of death was cancer in proximal and distal DVT patients. There were no significant differences in 90-day rates of recurrent VTE and major bleeding, regardless of the status of concomitant DVT (2.9%, 3.2%, and 2.2%, p = 0.79, and 1.5%, 4.4%, and 4.9%, p = 0.46, respectively). ConclusionsAcute PE with proximal DVT at diagnosis was associated with a higher risk for short-term mortality than in patients without DVT, while the risk for short-term mortality was not significantly different between distal DVT patients and patients without DVT.

Risk factors for major bleeding during prolonged anticoagulation therapy in cancer-associated venous thromboembolisms: from the COMMAND VTE registry

Abstract Background/Introduction Patients with cancer-associated venous thromboembolisms (VTEs) are at a high risk for recurrent VTEs 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 prolonged anticoagulation therapy. Purpose We aimed to identify the risk factors for major bleeding during prolonged anticoagulation therapy in cancer-associated VTE patients. Methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTEs among 29 Japanese centers between January 2010 and August 2014. After excluding those without active cancer (N=2332), patients with major bleeding (N=15), death (N=17), and lost to follow-up (N=10) within 10 days after the diagnosis, and those without anticoagulation therapy beyond 10 days after the diagnosis (N=61), the present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy beyond 10 days after the diagnosis. The outcome measurement was International Society of Thrombosis and Hemostasis (ISTH) major bleeding during anticoagulation therapy beyond 10 days, which occurred before the first discontinuation of the anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of the potential risk factors for major bleeding. As a sensitivity analysis, we used Fine and Gray's method to estimate the HR and 95% CI, taking into account the competing risk of all-cause death. Results During a median follow-up period of 199 days, major bleeding occurred in 72 patients (31 patients within 3 months; 41 beyond 3 months). The cumulative incidence of major bleeding was 5.8% at 3-months, 13.8% at 1-year, 17.5% at 2-year, and 28.1% at 5-years. The most frequent major bleeding site was gastrointestinal (47%), followed by intracranial (17%) and genitourinary (11%). Major bleeding tended to occur from the sites of the cancer, however, the sites of the cancer and sites of major bleeding were not necessarily concordant. The multivariable Cox regression model demonstrated that terminal cancer (adjusted HR, 4.17; 95% CI, 2.22–7.85, P&amp;lt;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. After taking into account the competing risk of all-cause death, the multivariable Cox regression model demonstrated almost consistent results with the main analysis. Conclusions Major bleeding events were common during prolonged 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. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Clinical characteristics and outcomes of patients with venous thromboembolism according to diagnosis on weekends versus weekdays: from the COMMAND VTE Registry

Abstract Background/Introduction The medical systems of hospitals often differs between on weekends and weekdays. These differences could lead different clinical outcomes for patients with acute medical conditions that require complex treatment strategies. However, the effect of the time of diagnosis on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is still controversial. Purpose We sought to evaluate the clinical characteristics and outcomes of patients with VTE comparing on weekends and weekdays in a large observational database of VTE in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. In the current analysis, diagnosis on weekends was defined as diagnosis during the period from 00:00 hours on Saturday to 24:00 on Sunday. All other times were defined as weekdays. We divided the entire cohort into 2 groups; diagnosis on weekends and diagnosis on weekdays groups, and we compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. Results The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. The median days from onset to diagnosis were shorter in the patients diagnosed on weekends than in those diagnosed on weekdays (2 days vs. 4 days, P&amp;lt;0.001). The patients diagnosed on weekends presented with PE more frequently (72% vs. 55%, P&amp;lt;0.001), and they showed more severe condition for PE with a higher simplified pulmonary embolism severity index score. The vast majority of PE patients were diagnosed by contrast-enhanced computed tomography in both groups (97% vs. 97%, P=0.67). 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 2 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) (Figure). After adjusting the confounders, the risk of diagnosis on weekends relative to diagnosis on weekdays for all-cause death among PE patients was still insignificant (adjusted HR: 0.76; 95% CI: 0.42–1.28). 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 days were not significantly different between the 2 groups among PE patients nor DVT patients. Conclusions The VTE patients diagnosed on weekends presented with PE more frequently, and they showed more severe condition for PE, although the risks for short-term mortality were not significantly different between patients diagnosed on weekends and weekdays. Kaplan-Meier curves for all-cause death Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Predictive ability of modified Ottawa score for recurrence in patients with cancer-associated venous thromboembolisms: from the COMMAND VTE Registry

Abstract Background/Introduction Patients with cancer-associated venous thromboembolisms (VTEs) have a markedly higher risk of recurrence as well as bleeding, compared to those without, leading to difficulty in achieving a good risk-to-benefit balance with anticoagulation therapy. Thus, the assessment of the risk of recurrence in an individual patient is essential. The modified Ottawa score has been developed to predict the risk of recurrence in patients with cancer-associated VTEs during anticoagulation therapy, however, the validity of the score is still controversial. Purpose We aimed to evaluate the utility and limitations of the modified Ottawa score in the risk stratification of recurrent VTEs in patients with cancer-associated VTEs. Methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTEs among 29 Japanese centers between January 2010 and August 2014. The present study population consisted of 614 cancer-associated VTE patients with anticoagulation therapy beyond 10 days after the diagnosis, who were divided into 3 groups; High-risk group with a modified Ottawa score ≥1, Intermediate-risk group with a score = 0, and Low-risk group with a score ≤−1. To evaluate the discriminating power of the modified Ottawa score for recurrence, we described the receiver operating characteristic curve with a C-statistic, and evaluated the positive likelihood ratio as the predictive performance of the score for recurrence in each subgroup. Results The high-risk group accounted for 202 patients (33%), intermediate-risk group for 269 (44%), and low-risk group for 143 (23%). During the first 6 months of anticoagulation therapy, recurrent VTEs occurred in 39 patients. The cumulative incidence of recurrent VTEs substantially increased in the higher risk categories by the modified Ottawa score (High-risk group: 13.6%, Intermediate-risk group: 5.9%, and Low-risk group: 3.0%, Log-rank P=0.02) (Figure 1). The discriminating power of the score was modest with a C-statistic of 0.63 (95% CI 0.55–0.71). The positive likelihood ratios as the predictive performance of the score were 1.71 in the high-risk group, 0.81 in the intermediate-risk group, and 0.42 in the low-risk group. Women and patients with prior VTEs had numerically higher cumulative 6-month incidences of recurrent VTEs compared with those without, while patients with lung cancer, breast cancer, and without metastasis had numerically lower cumulative 6-month incidences of recurrent VTEs. Depending on the presence or absence of each score component, the risks of recurrence seemed to differ in the low-, intermediate-, and high-risk groups. Conclusions The risks of recurrence in patients with cancer-associated VTEs substantially increased in the higher risk categories by using the modified Ottawa score, but the discriminating power of the score for recurrence was modest with a widely variable impact of each score component on recurrence. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

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

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. 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.

Long-term effects of non-retrieved inferior vena cava filters on recurrences of venous thromboembolism in cancer and non-cancer patients: From the COMMAND VTE registry

There is a paucity of data comparing the long-term outcomes after inferior vena cava (IVC) filters placement for patients with acute venous thromboembolism (VTE) between those with and without active cancer. In the COMMAND VTE Registry, we evaluated the effects of IVC filter use on the long-term clinical outcomes stratified by the presence and absence of active cancer. Among 2,626 patients with acute symptomatic VTE, there were 604 patients with active cancer, and 2022 patients without active cancer. IVC filters were placed and not retrieved in 455 patients (17%) in the entire cohort, in 150 patients (24.8%) in the active cancer stratum, and in 305 patients (15.1%) in the non-cancer stratum. In the entire cohort, non-retrieved IVC filter placement was not associated with a lower adjusted risk for PE recurrence (HR 0.59, 95% CI 0.30-1.15, P=0.122), but with an increased adjusted risk for DVT recurrence (HR 2.27, 95% CI 1.43-3.60, P<0.001). In the non-cancer stratum, the non-retrieved IVC filter placement was associated with a decreased risk for PE (HR 0.29, 95% CI 0.09-0.93, P=0.037), but not with an increased risk for DVT (HR 1.73, 95% CI 0.89-3.38, P=0.108), while in the active cancer stratum, it was associated with an increased risk for DVT (HR 2.47, 95% CI 1.24-4.91, P=0.010), but not with a decreased risk for PE (HR 0.82, 95% CI 0.34--1.96, P=0.650). There were some differences in the risk-benefit balance between VTE patients with and without active cancer.

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.