Venous Thromboembolism Registry Research Articles

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.

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

The 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. Analyze 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. We compared the rates and CFRs in patients of the RIETE and COMMAND-VTE registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding. Of 8,261 patients with unprovoked VTE in RIETE, 4,012 (48.6%) had isolated deep vein thrombosis (DVT) and 4,250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The COMMAND VTE 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. Recurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. Contrary, major bleeding was rare, but had high CFR (24%). A few clinical factors may predict these outcomes.

Subclass phenotypes in patients with unprovoked venous thromboembolisms using a latent class analysis

BackgroundPatients with unprovoked venous thromboembolisms (VTEs) can be sub-classified based on the different phenotypes using a latent class analysis (LCA), which might be useful for selecting individual management strategies. MethodsIn the COMMAND VTE Registry-2 database enrolling 5197 VTE patients, the current derivation cohort consisted of 1556 patients with unprovoked VTEs. We conducted clustering with an LCA, and the patients were classified into subgroups with the highest probability. We compared the clinical characteristics and outcomes among the developed subgroups. ResultsThis LCA model proposed 3 subgroups based on 8 clinically relevant variables, and classified 592, 813, and 151 patients as Class I, II, and III, respectively. Based on the clinical features, we named Class I the younger, Class II the older with a few comorbidities, and Class III the older with many comorbidities. The cumulative 3-year anticoagulation discontinuation rate was highest in the older with many comorbidities (Class III) (39.9 %, 36.1 %, and 48.4 %, P = 0.02). There was no significant difference in the cumulative 5-year incidence of recurrent VTEs among the 3 classes (12.8 %, 11.1 %, and 4.0 % P = 0.20), whereas the cumulative 5-year incidence of major bleeding was significantly higher in the older with many comorbidities (Class III) (7.8 %, 12.7 %, and 17.8 %, P = 0.04). ConclusionThe current LCA revealed that patients with unprovoked VTEs could be sub-classified into further phenotypes depending on the patient characteristics. Each subclass phenotype could have different clinical outcomes risks especially a bleeding risk, which could have a potential benefit when considering the individual anticoagulation strategies. Clinical trial registrationURL: http://www.umin.ac.jp/ctr/index.htmCOMMAND VTE Registry-2: Unique identifier, UMIN000044816COMMAND VTE Registry: Unique identifier, UMIN000021132

Extended Full Dose Versus Low Dose Direct Oral Anticoagulants in Cancer and Overweight Patients

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at full, therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unclear. Aims: Examine the effectiveness, safety and utilization of reduced-dose DOACs in cancer patients and overweight patients. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st, 2013 to December 31st, 2021. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Patients with recurrent VTE or bleeding during the first 3 months were excluded from further analysis. After completion of anticoagulation treatment for 3 months with either rivaroxaban or apixaban, patients continuing anticoagulation were evaluated in a nested case-control study. Results: A total of 404 patients (283 (70%) on apixaban and 121 (30%) on rivaroxaban) were identified in the low dose DOAC and 3060 in the full dose anticoagulation group. Overall, the mean age was 60.7 years (SD 14.4), mean weight was 89.9 kg (SD 23.8) and 55.1% were males. Within the full cohort, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; p&amp;lt;0.001). However, low dose DOAC prescription was more likely in patients with pulmonary embolism alone (HR 1.48; 95%CI 1.21-1.80; p&amp;lt;0.001) or in combination with DVT (HR 1.54; 95%CI 1.25,1.90; p&amp;lt;0.001). Patients transitioned to low dose DOACs had similar age, sex and weight compared to the full dose anticoagulation group, however, fewer patients with weight ≥120 kg had reduced dosing (HR 0.68; 95%CI 0.46,0.99; p=0.046). The mean time to start of a low dose DOAC was 5.1 months overall, 5.4 months in cancer patients, and 3.6-4.9 months in non-cancer patients (Table 1). Non-cancer patients had significantly lower transition numbers in those ≥120kg (HR 0.62; 95%CI 0.40,0.97; p=0.038). In non-cancer patients In comparing weight, ≥120kg to &amp;lt;120kg, in the low dose group, only death was statistically different with higher risk in those ≥120kg (HR 6.44; 95%CI1.27,32.81; p=0.025). Cancer patients transitioned to low dose DOACs around 5 months on average with a median of 3.3 months. Apixaban continued to be the dominant DOAC used (78%) in the low dose group. The cancers with the most patients on low dose DOACs include lymphoma, prostate, melanoma, ovarian, and breast. There was no significant difference in VTE recurrence or death in the cancer group on different DOAC doses. Conclusion: Our results show that anticoagulant prescribers are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients despite lack of cancer-specific studies during the analyzed time period. Although the sample size limits the precision of this analysis, we did not find statistically significant increases in VTE recurrence with low dose DOACs in either cancer patients or with elevated body weight. We did find CRNMB but not MB was observed more frequently in weights above 120kg, possibly from unadjusted confounding in this unadjusted analysis.

Clinical characteristics and outcomes of super-low-dose edoxaban of 15 mg in patients with acute venous thromboembolism: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction The current guidelines recommend specific durations of anticoagulation therapy depending on the risks of recurrent venous thromboembolism (VTE), and prolonged anticoagulation therapy is recommended for patients at not-low risk of recurrence. However, clinicians are sometimes reluctant to continue anticoagulation therapy for patients with high-bleeding risk. A recent study reported that super-low-dose edoxaban of 15 mg was useful in preventing thromboembolic events for elderly patients with atrial fibrillation who were considered as high-bleeding risk patients. However, super-low-dose edoxaban of 15 mg is currently off-label for VTE all over the world, which could be a potential option for patient with VTE at high-bleeding risk. Purpose The current study aimed to investigate clinical characteristics and outcomes of VTE patients with super-low-dose edoxaban of 15 mg, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. After excluding 3193 patients without edoxaban as oral anticoagulation therapy, the current study population was consisted of 2004 patients with edoxaban, who were divided into 3 groups according to initial dosage of edoxaban; 60 mg/day (N=664, 33%) 30 mg/day (N=1309, 65%) and 15 mg/day (N=31, 1.5%). Results Patients with edoxaban of 15 mg/day were oldest (60 mg/day: 62.3 years, 30 mg/day: 72.9 years and 15 mg/day: 79.2 years, P&amp;lt;0.001), were most often women (44%, 73% and 84%, P&amp;lt;0.001), showed a lowest mean body weight (68.4, 51.9 and 48.7 kg, P&amp;lt;0.001). Pulmonary embolism as initial presentation was least frequent in patients with edoxaban of 15 mg/day (58%, 44% and 13%, P&amp;lt;0.001). Patients with edoxaban of 15 mg/day most frequently had chronic kidney disease (10%, 22% and 26%, P&amp;lt;0.001) and anemia (45%, 66% and 74%, P&amp;lt;0.001). The discontinuation rates of anticoagulation therapy were not significantly different among the 3 groups (54.4%, 56.5% and 64.8% at 3-year, Log rank P=0.38). The cumulative incidences of recurrent VTE were not significantly different among the 3 groups (6.0%, 6.6% and 0.0% at 3-year, Log rank P=0.31). Similarly, the cumulative incidences of major bleeding were not significantly different among the 3 groups (9.2%, 11.6% and 15.3% at 3-year, Log rank P=0.11). Conclusions In the current real-world large VTE registry, a very minority of VTE patients received edoxaban of 15 mg/day, including patients at high-bleeding risk such as old age, low body weight and chronic kidney disease, who did not show significant worse outcomes in terms of recurrent VTE.

Abstract 14258: Are Anticoagulants Necessary for Isolated Distal Deep Vein Thrombosis? From COMMAND VTE Registry 1 and 2

Background: Anticoagulation for isolated distal deep vein thrombosis (DVT) remains controversial and is rarely recommended; however, all available data are from the warfarin era, and the effects of DOACs remain unknown. Objective and Methods: A large cohort of patients with acute venous thrombosis in the Contemporary Management and Outcomes in Patients with Venous Thromboembolism Registry (COMMAND VTE Registry 1 and 2) in Japan were included for analysis. We then evaluated the patient characteristics, clinical outcomes of symptomatic isolated distal DVT, and the risk-benefit of anticoagulation therapy by comparing direct oral anticoagulant (DOAC) and warfarin. Results: From a total of 8224 patients in the COMMAND registry, we excluded those with isolated distal DVT who had an event within 30 days of the initial venous thrombosis, leaving 1054 patients for the study. Among the 1054 patients included, 599, 312 and 143 were on DOACs, warfarin and no anticoagulant respectively. Overall, Kaplan-Meier analysis during a median follow-up of 988 days showed that anticoagulation significantly prevented recurrent VTE (P = 0.011), with no difference between warfarin and DOACs (P = 0.862). No clear increase in bleeding events were observed regardless of anticoagulation status (P = 0.327). Subsequent analysis stratified entries into transient (N = 318), Persistent (N = 353), and Unprovoked (N = 383) groups according to risk of venous thrombosis. In the persistent group, anticoagulation significantly prevented recurrent VTE (P = 0.025), with no difference between DOAC and warfarin (P = 0.939). In the transient group, anticoagulation was not effective in preventing recurrent VTE, with warfarin use significantly increasing bleeding events compared to those with DOAC or no anticoagulation (P = 0.030). Multivariate analysis showed that anticoagulation was independently associated with decreased incidence of venous thrombosis in the persistent group [HR: 0.262 (0.094-0.727), P = 0.010]. Conclusion: In symptomatic isolated distal DVT, anticoagulation is effective in preventing exacerbation of venous thrombosis; however, warfarin may increase bleeding events among the patients with transient DVT risk.

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.

Anticoagulation strategies and long-term recurrence in patients with venous thromboembolism in the era of direct oral anticoagulants

BackgroundThere has been limited data on anticoagulation strategies and long-term recurrence in patients with venous thromboembolism (VTE) in the era of direct oral anticoagulant (DOAC). MethodsThe COMMAND VTE Registry-2 is a multicenter retrospective cohort study enrolling 5197 consecutive patients with acute symptomatic VTE between January 2015 and August 2020 among 31 centers in Japan. In this primary report, the entire cohort was divided into 5 groups; major transient risk factors (N = 475, 9.1%), minor transient risk factors (N = 788, 15%), unprovoked (N = 1913, 37%), non-malignant persistent risk factors (N = 514, 9.9%), and active cancer (N = 1507, 29%) groups. ResultsDOACs were administered in 79% of patients who received oral anticoagulants. Discontinuation of anticoagulant at 1 year was most frequent in the major transient risk factors group (57.2%, 46.3%, 29.1%, 32.0%, and 45.6%). The cumulative 5-year incidence of recurrent VTE was lowest in the major transient risk factors group (2.6%, 6.4%, 11.0%, 12.1%, and 10.1%, P < 0.001). The cumulative 5-year incidence of major bleeding was highest in the active cancer group (9.8%, 11.4%, 11.0%, 15.5%, and 20.4%, P < 0.001). After discontinuation of anticoagulation therapy, the cumulative 5-year incidence of recurrent VTE was highest in the unprovoked group (3.3%, 11.0%, 24.9%, 17.5%, and 11.8%, P < 0.001). ConclusionsIn this large real-world VTE registry, anticoagulation strategies and long-term recurrence widely differed depending on the baseline characteristics. Detailed risk stratifications of recurrent VTE could be useful for decision-making of anticoagulation strategies, whereas the bleeding-risk assessment might be especially important in the era of DOAC. Clinical Trial RegistrationURL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

Development of prospective hospital-based venous thromboembolism registry across India: a study protocol

IntroductionIndian Council of Medical Research (ICMR), New Delhi has established a nationwide registry ‘Indian Registry for Venous Thromoembolism Disorder (i-RegVeD)’ for real-time analytics of sociodemographic profile of patients, disease patterns,...

The clinical outcomes of different doses of rivaroxaban in patients with isolated distal deep vein thrombosis

ObjectiveIsolated distal deep vein thrombosis (IDDVT) is defined as thrombosis involving the infrapopliteal veins. The optimal anticoagulant therapy of IDDVT remains controversial. This study aimed to assess whether reduced dose of rivaroxaban was suitable in patients with IDDVT. MethodsConsecutive patients with acute IDDVT were identified by reviewing the venous thromboembolism (VTE) registry databases. Outcomes including VTE recurrence, major bleeding, clinically relevant non-major (CRNM) bleeding, and death. Patients were followed until the first occurrence of any outcomes or the study end date (December 31, 2018). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. ResultsA total of 1246 patients were divided into low-dose (10 or 15 mg/day; n = 716) and standard-dose (20 mg/day; n = 530) groups. The incidences of VTE recurrence, major bleeding, CRNM bleeding, and death between the two groups were 9.64% vs 5.66%, 1.68% vs 3.02%, 4.61% vs 8.68%, and 13.83% vs 10.75%, respectively. After the inverse probability of treatment weighting, HRs for standard-dose vs low-dose of VTE recurrence, major bleeding, CRNM bleeding, and death were 0.54 (95% CI, 0.35-0.84), 1.71 (95% CI, 0.80-3.67), 2.28 (95% CI, 1.40-3.74), and 1.30 (95% CI, 0.91-1.86), respectively. For the subgroup analysis, the interaction with anticoagulation duration and treatment was evident for VTE recurrence (P for interaction = .002), but not for major bleeding. Patients with residual vein thrombosis were associated with an increased risk of VTE recurrence (HR, 1.95; 95% CI, 1.29-2.95). The interaction between risk factors and residual vein thrombosis was evident for VTE recurrence (P for interaction = .085). ConclusionsStandard-dose rivaroxaban reduced the risk of VTE recurrence without increasing the risk of major bleeding in patients with IDDVT. Anticoagulant therapy for >1.5 months should be preferred over shorter durations. Residual vein thrombosis should be assessed as a predictor of recurrence in patients with IDDVT, especially for patients with non-transient factors.

Predicting acute and long-term mortality in a cohort of pulmonary embolism patients using machine learning

BackgroundPulmonary embolism (PE) is a severe condition that causes significant mortality and morbidity. Due to its acute nature, scores have been developed to stratify patients at high risk of 30-day mortality. Here we develop a machine-learning based score to predict 30-day, 90-day, and 365-day mortality in PE patients. MethodsThe Birmingham and Black Country Venous Thromboembolism registry (BBC-VTE) of 2183 venous thromboembolism patients is used. Random forests were trained on a 70% training cohort and tested against 30% held-out set. The outcomes of interest were 30-day, 90-day, and 365-day mortality. These were compared to the pulmonary embolism severity index (PESI) and simplified pulmonary embolism severity index (sPESI). Shapley values were used to determine important predictors. Oral anticoagulation at discharge was also investigated as a predictor of mortality. ResultsThe machine learning risk score predicted 30-day mortality with AUC 0.71 [95% CI: 0.63 - 0.78] compared to the sPESI AUC of 0.65 [95% CI: 0.57 - 0.73] and PESI AUC of 0.64 [95% CI: 0.56 – 0.72]. 90-day mortality and 365-day mortality were predicted with an AUC of 0.74 and 0.73 respectively. High counts of neutrophils, white blood cell counts, and c-reactive protein and low counts of haemoglobin were important for 30-day mortality prediction but progressively lost importance with time. Older age was an important predictor of high risk throughout. ConclusionMachine learning algorithms have improved on standard clinical risk stratification for PE patients. External cohort validation is required before incorporation into clinical workflows.

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.

Predictors of use of direct oral anticoagulants in patients with venous thromboembolism: Findings from the Registro Informatizado Enfermedad Tromboembólica registry.

Current guidelines recommend the use of direct oral anticoagulants (DOACs) for patients with venous thromboembolism (VTE). However little is known about the use of DOACs in daily practice. We used the RIETE registry to identify predictors of use of DOACs for initial and/or long-term therapy of VTE based on patient-related factors, institution-related factors or over time. Among 41,678 patients from March 2013 to September 2021, 12,286 (29%) used DOACs: for initial therapy 6,456; for long-term therapy 12,046. On multivariable analysis, independent predictors were: age < 65 years (odds ratio [OR]: 1.30; 95% CI: 1.23-1.38), body weight <50 kg (OR: 0.54; 95% CI: 0.45-0.65) or >120 kg (OR: 0.64; 95% CI: 0.53-0.77), initial VTE presentation as pulmonary embolism (OR: 1.18; 95% CI: 1.13-1.25), recent bleeding (OR: 0.53; 95% CI: 0.45-0.63), renal insufficiency (OR: 0.44; 95% CI: 0.38-0.51), liver cirrhosis (OR: 0.32; 95% CI: 0.20-0.52), thrombocytopenia (OR: 0.40; 95% CI: 0.34-0.49), atrial fibrillation (OR: 1.58; 95% CI: 1.42-1.75) and prior VTE (OR: 1.14; 95% CI: 1.06-1.22). The DOACs were more likely used in other European countries (OR: 8.97; 95% CI: 8.49-9.49), America (OR: 6.35; 95% CI: 5.67-7.11) or in other countries of the world (OR: 2.99; 95% CI: 2.70-3.31) than in Spain, and progressively increased from 2013-2015 to 2016-2018 (OR: 2.78; 95% CI: 2.62-2.95) and 2019-2021 (OR: 6.36; 95% CI: 5.95-6.80). In this large multinational VTE registry, variations were observed in the use of DOACs according to patient or country factors, and over time. The safety, costs, and influence of the DOACs on VTE-related outcomes in daily practice warrant further investigation.

Differences in duration of anticoagulation after pulmonary embolism and deep vein thrombosis: Findings from the SWIss Venous ThromboEmbolism Registry (SWIVTER)

BackgroundAlthough the two manifestations of venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE), vary considerably, the consensus guidelines recommend similar algorithms for therapeutic anticoagulation in both conditions. Real-world data assessing contemporary management strategies in PE and DVT alone may help tailoring future recommendations towards more individualized patient care. MethodsIn the present analysis, we compared demographics, comorbidities, treatment patterns, and clinical outcomes of PE versus DVT only among 2062 consecutive patients with confirmed VTE enrolled by 11 acute care hospitals between November 2012 and February 2015 in the SWIss Venous ThromboEmbolism Registry (SWIVTER). ResultsOverall, 1246 (60 %) patients were diagnosed with PE. In comparison to DVT alone, PE patients were older (66 vs. 59 years; p < 0.001), more frequently had acute and chronic comorbidities, less frequently had prior VTE and hormone replacement, and were less often pregnant. VTE was considered similarly often provoked in patients with PE and DVT alone (33.8 % vs. 33.5 %; p = 0.88). Anticoagulation for an indefinite duration was more often prescribed to patients with PE than those with DVT alone (45.7 vs. 19.6 %; p < 0.001), and PE diagnosis was the strongest independent predictor of indefinite anticoagulation (OR 3.21; 95 % CI 2.55–4.06; p < 0.001). Diagnosis of PE was associated with both increased risk of 90-day mortality (HR 2.31, 95 % CI 1.44–3.71; p = 0.001) and major bleeding (HR 3.88, 95 % CI 1.63–9.22; p = 0.002). ConclusionsOur analysis affirms differences in demographics, risk factors, and clinical outcomes of PE versus DVT alone. In routine clinical practice, duration of anticoagulation is being managed differently between the two manifestations of VTE, in contrast to recommendations of the current consensus guidelines.

Venous thromboembolism and mortality in a multiethnic population: a report from the Birmingham Black Country VTE registry (BBC-VTE Investigators)

Abstract Background Most epidemiological studies into venous thromboembolism (VTE) are based on the white Caucasian population and unrepresentative of VTE outcomes in non-white ethnicities. Purpose Our VTE registry aims to get an insight into the outcomes of VTE patients as applicable to a developed world population with a multi-ethnic background. This will guide clinicians to make appropriate decisions with regards to management and prognosis. Methods The Birmingham Black Country VTE Registry (BBC-VTE) is a multi-ethnic cohort of patients in the West Midlands region of the United Kingdom, who suffered a first episode of VTE. In this study we compared baseline characteristics, treatment patterns and outcomes, and secondly, compared these among the different ethnic groups in this region. Results Between the years 2012–2014 there was a total of 1615 patients (mean age 65.5; 53.1% female) admitted with a first episode of VTE of whom, 134 (8.3%) were Asian, 92 (5.7%) Black, and 1213 (75.1%) White. Asian patients were younger (mean age 54, SD 19.3) vs Black patients (59, SD 19.7) and White patients (68, SD 17.4); and were less often female (50.7% vs. 55.4% and 53.8%) for Black and White patients respectively. The initial VTE event was a DVT in 680 (42.1%) and a PE±DVT in 935 patients (57.9%). Below-knee and above-knee DVT occurred in 95 (5.9%) and 585 (36.2%) patients respectively. Recurrent DVT occurred in 3.2% of those with an initial below-knee DVT and 12.5% of those with an initial above-knee DVT. Recurrent PE was also more common in those with an initial above knee DVT (4.8%) compared to those with below-knee DVT (3.2%). After the initial VTE event, 1269 (78.6%) were started on long-term anticoagulation for the prevention of recurrent VTE. Of those, 65.1% stayed on anticoagulation for up to 6 months after the initial VTE event, and 34.9% continued for longer than 6 months, including those on lifelong anticoagulation. Bleeding and major bleeding occurred in 6.8% and 2.5% respectively in those on anticoagulation for 6 or less months, vs. 10.4% and 3.5% in those anticoagulated for longer than 6 months. The most common site of bleeding was gastrointestinal in 42.3% of all bleeds and this site was also responsible for 54.3% of major bleeds. From evaluating the odds ratio for VTE mortality (see Fig. 1), ethnicity did not have a significant impact. Older age; the presence of diabetes mellitus; history of malignancy; as well as admission laboratory results for C-reactive protein and neutrophil count were all significantly associated with higher odds of mortality in this patient cohort. Conclusion BBC-VTE is a contemporary multi-ethnic cohort of patients providing insights into the risk factors among multi-ethnic patients that have developed VTE. Ethnicity did not emerge as an independent risk for VTE mortality. Funding Acknowledgement Type of funding sources: None.

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.

The venous thrombosis registry in Østfold Hospital (TROLL registry) ‐ design and cohort description

PurposeThe incidence of venous thromboembolism (VTE) is expected to increase over the next decades, further increasing its substantial impact on patients and health care resources. Registries have the benefit of reporting real‐world data without excluding clinically important subgroups. Our aim was to describe a Norwegian VTE registry and to provide descriptive data on the population and management. Registry PopulationThe Venous Thrombosis Registry in Østfold Hospital (TROLL) is an ongoing registry of consecutive patients diagnosed with, treated, and/or followed up for VTE at Østfold Hospital, Norway, since 2005. Baseline and follow‐up data, including demographics, clinical features, risk factors, diagnostic procedures, classification of VTE, and treatment were collected during hospitalization, and at scheduled outpatient visits. Findings to DateFrom January 2005 to June 2021, 5037 patients were eligible for research in TROLL. Median age was 67 years (interquartile range, 55–77), and 2622 (52.1%) were male. Of these, 2736 (54.3%) had pulmonary embolism (PE), 2034 (40.4%) had deep vein thrombosis (DVT), and 265 (5.3%) had upper‐extremity DVT or splanchnic or cerebral sinus vein thrombosis. In total, 2330 (46.3%) were classified as unprovoked VTE, and 1131 (22.5%) had cancer. Direct oral anticoagulants were the most frequent therapeutic agents (39.3%) followed by low‐molecular‐weight heparins (30.4%) and vitamin K antagonists (30.3%). Outpatient treatment for PE increased from 4% in 2005 to 23% in 2019. Future PlansTROLL is a population‐based ongoing registry that represents a valuable source of real‐world data that will be used for future research on the management and outcomes of VTE.

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.