Assessment of Outcomes Among Patients With Venous Thromboembolism With and Without Chronic Kidney Disease

Importance: Patients with venous thromboembolism (VTE) and concomitant chronic kidney disease (CKD) have been reported to have a higher risk of thrombosis and major bleeding complications compared with patients without concomitant CKD. The use of anticoagulation therapy is challenging, as many anticoagulant medications are excreted by the kidney. Large-scale data are needed to clarify the impact of CKD for anticoagulant treatment strategies and clinical outcomes of patients with VTE. Objective: To compare clinical characteristics, treatment patterns, and 12-month outcomes among patients with VTE and concomitant moderate to severe CKD (stages 3-5) vs patients with VTE and mild to no CKD (stages 1-2) in a contemporary international registry. Design, Setting, and Participants: The Global Anticoagulant Registry in the Field–Venous Thromboembolism (GARFIELD-VTE) study is a prospective noninterventional investigation of real-world treatment practices. A total of 10 684 patients from 415 sites in 28 countries were enrolled in the GARFIELD-VTE between May 2014 and January 2017. This cohort study included 8979 patients (6924 patients with mild to no CKD and 2055 patients with moderate to severe CKD) who had objectively confirmed VTE within 30 days before entry in the registry. Chronic kidney disease stages were defined by estimated glomerular filtration rates. Data were extracted from the study database on December 8, 2018, and analyzed between May 1, 2019, and July 30, 2020. Exposure: Moderate to severe CKD vs mild to no CKD. Main Outcomes and Measures: The primary outcomes were all-cause mortality, recurrent VTE, and major bleeding. Event rates and 95% CIs were calculated and expressed per 100 person-years. Hazard ratios (HRs) were estimated with Cox proportional hazards regression models and adjusted for relevant confounding variables. All-cause mortality was considered a competing risk for other clinical outcomes in the estimation of cumulative incidences. Results: Of the 10 684 patients with objectively confirmed VTE, serum creatinine data were available for 8979 patients (84.0%). Of those, 4432 patients (49.4%) were female and 5912 patients (65.8%) were White; 6924 patients (77.1%; median age, 57 years; interquartile range [IQR], 44-69 years) were classified as having mild to no CKD, and 2055 patients (22.9%; median age, 70 years; IQR, 59-78 years) were classified as having moderate to severe CKD. Calculations using the equation from the Modification of Diet in Renal Disease study indicated that, among the 6924 patients with mild to no CKD, 2991 patients had stage 1 CKD, and 3933 patients had stage 2 CKD; among the 2055 patients with moderate to severe CKD, 1650 patients had stage 3 CKD, 190 patients had stage 4 CKD, and 215 patients had stage 5 CKD. The distribution of VTE presentation was comparable between groups. In total, 1171 patients (57.0%) with moderate to severe CKD and 4079 patients (58.9%) with mild to no CKD presented with deep vein thrombosis alone, 547 patients (26.6%) with moderate to severe CKD and 1723 patients (24.9%) with mild to no CKD presented with pulmonary embolism alone, and 337 patients (16.4%) with moderate to severe CKD and 1122 patients (16.2%) with mild to no CKD presented with both pulmonary embolism and deep vein thrombosis. Compared with patients with mild to no CKD, patients with moderate to severe CKD were more likely to be female (3259 women [47.1%] vs 1173 women [57.1%]) and older than 65 years (2313 patients [33.4%] vs 1278 patients [62.2%]). At baseline, the receipt of parenteral therapy alone was comparable between the 2 groups (355 patients [17.3%] with moderate to severe CKD vs 1253 patients [18.1%] with mild to no CKD). Patients with moderate to severe CKD compared with those with mild to no CKD were less likely to be receiving direct oral anticoagulant therapy, either alone (557 patients [27.1%] vs 2139 patients [30.9%]) or in combination with parenteral therapy (319 patients [15.5%] vs 1239 patients [17.9%]). Patients with moderate to severe CKD had a higher risk of all-cause mortality (adjusted hazard ratio [aHR], 1.44; 95% CI, 1.21-1.73), major bleeding (aHR, 1.40; 95% CI, 1.03-1.90), and recurrent VTE (aHR, 1.40; 95% CI, 1.10-1.77) than patients with mild to no CKD. Conclusions and Relevance: In this study of patients with VTE, the presence of moderate to severe CKD was associated with increases in the risk of death, VTE recurrence, and major bleeding compared with the presence of mild to no CKD

The influence of anemia on clinical outcomes in venous thromboembolism: Results from GARFIELD-VTE.

INTRODUCTION: Clinical characteristics and outcomes of venous thromboembolism (VTE) patients with concomitant anemia are unclear. This study compares baseline characteristics, treatment patterns, and 24-month outcomes in patients with and without anemia within GARFIELD-VTE. MATERIALS AND METHODS: GARFIELD-VTE (ClinicalTrials.gov: NCT02155491) is a global, prospective, non-interventional registry of real-world treatment practices. Of the 10,679 patients enrolled in GARFIELD-VTE, 7698 were eligible for analysis. Primary outcomes were all-cause mortality, recurrent VTE, and major bleeding in VTE patients with or without concomitant anemia over 24-months after diagnosis. Event rates and 95% confidence intervals were estimated using Poisson regression. Adjusted hazard ratios were calculated using Cox proportional hazard models. RESULTS: Distribution of VTE events in 2771 patients with anemia and 4927 without anemia was similar (deep-vein thrombosis alone: 61·1% vs. 55·9%, pulmonary embolism ± deep vein thrombosis: 38·9% vs. 44·0%, respectively). Patients with anemia were older (62.6 year vs. 58.9 years) than those without. At baseline, VTE risk factors that were more common in patients with anemia included hospitalization (22·0% vs. 6·8%), surgery (19·2% vs. 8·2%), cancer (20·1% vs. 5·6%) and acute medical illness (8·3% vs. 4·2%). Patients with anemia were more likely to receive parenteral anticoagulation therapy alone than those without anemia (26·6% vs. 11·7%) and less likely to receive a direct oral anticoagulant (38·5% vs. 53·5%). During 24-months of follow-up, patients with anemia had a higher risk (adjusted hazard ratio [95% confidence interval]) of all-cause mortality (1·84 [1·56-2·18]), major bleeding (2·83 [2·14-3·75]). Among anemia patients, the risk of all-cause mortality and major bleeding remained higher in patients with severe anemia than in those with mild/moderate anemia, all-cause mortality: HR 1·43 [95% CI: 1·21-1·77]; major bleeding: HR 2·08 [95% CI: 1·52-2·86]). CONCLUSIONS: VTE patients with concomitant anemia have a higher risk of adverse clinical outcomes compared with those without anemia. Further optimization of anticoagulation therapy for VTE patients with anemia is warranted

Pregnancy-Associated Venous Thromboembolism: Insights from GARFIELD-VTE.

Introduction  The risk of venous thromboembolism (VTE) increases during pregnancy and the puerperium such that VTE is a leading cause of maternal mortality. Methods  We describe the clinical characteristics, diagnostic strategies, treatment patterns, and outcomes of women with pregnancy-associated VTE (PA-VTE) enrolled in the Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE. Women of childbearing age (<45 years) were stratified into those with PA-VTE ( n  = 183), which included pregnant patients and those within the puerperium, and those with nonpregnancy associated VTE (NPA-VTE; n  = 1,187). Patients with PA-VTE were not stratified based upon the stage of pregnancy or puerperium. Results  Women with PA-VTE were younger (30.5 vs. 34.8 years), less likely to have pulmonary embolism (PE) (19.7 vs. 32.3%) and more likely to have left-sided deep vein thrombosis (DVT) (73.9 vs. 54.8%) compared with those with NPA-VTE. The most common risk factors in PA-VTE patients were hospitalization (10.4%), previous surgery (10.4%), and family history of VTE (9.3%). DVT was typically diagnosed by compression ultrasonography (98.7%) and PE by chest computed tomography (75.0%). PA-VTE patients more often received parenteral (43.2 vs. 15.1%) or vitamin K antagonists (VKA) (9.3 vs. 7.6%) therapy alone. NPA-VTE patients more often received a DOAC alone (30.2 vs. 13.7%). The risk (hazard ratio [95% confidence interval]) of all-cause mortality (0.59 [0.18-1.98]), recurrent VTE (0.82 [0.34-1.94]), and major bleeding (1.13 [0.33-3.90]) were comparable between PA-VTE and NPA-VTE patients. Uterine bleeding was the most common complication in both groups. Conclusion  VKAs or DOACs are widely used for treatment of PA-VTE despite limited evidence for their use in this population. Rates of clinical outcomes were comparable between groups

Influence of Body Mass Index on Clinical Outcomes in Venous Thromboembolism: Insights from GARFIELD-VTE.

BACKGROUND: There is limited information on the influence of body mass index (BMI) on clinical outcomes in patients with venous thromboembolism (VTE). OBJECTIVES: Investigate the influence of BMI on baseline characteristics, treatment patterns, and 24-month outcomes in VTE patients. METHODS: GARFIELD-VTE is a prospective, non-interventional study of 10,869 patients with objectively confirmed VTE. Patients were grouped according to BMI: <18.5 (underweight; n=214); 18.5-24.9 (normal; n=2866); 25.0-29.9 (overweight; n=3326); ≥30 (obese; n=3073). RESULTS: Compared with patients with a normal BMI, obese patients were more frequently Caucasian (77.4% vs. 57.9%), treated in the outpatient setting (30.4% vs. 23.1%), and had previous VTE (17.5% vs. 11.7%). Active cancer was associated with lower BMI (underweight:30.4%, normal:13.5%, overweight:9.4%, obese:7.0%). At baseline, overweight and obese patients less often received parenteral therapy alone (16.7% and 14.4%) compared with those with an underweight or normal BMI (30.8% and 21.6%). Obese patients more commonly remained on anticoagulants for ≥2-years compared to those with a normal BMI (52.3% vs. 37.7%). After 24-months, the risk of all-cause mortality was lower in overweight and obese patients than in those with normal BMI (adjusted hazard ratio [95% CI]; 0.75 [0.63-0.89] and 0.59 [0.49-0.72], respectively). Underweight patients more often experienced major bleeding (2.45 [1.41-4.26]) and all-cause mortality (1.90 [1.43-2.53]) than patients with a normal BMI. Recurrent VTE was comparable among groups. CONCLUSION: Underweight VTE patients have the highest risk of mortality and major bleeding. The risk of mortality in obese VTE patients is lower than that in VTE patients with a normal BMI

Management strategies and clinical outcomes in patients with inferior vena cava thrombosis: Data from GARFIELD-VTE

BACKGROUND: Inferior vena cava (IVC) thrombosis is a rare form of venous thromboembolism (VTE). The optimal treatment strategies and outcomes are unclear in patients with this presentation. OBJECTIVE: We aimed to compare baseline characteristics, treatment patterns and 24‐month outcomes in IVC thrombosis patients (n = 100) with lower extremity deep vein thrombosis (LEDVT) patients (n = 7629). METHODS: GARFIELD–VTE is a prospective, observational registry of 10 868 patients with objectively diagnosed VTE from 415 sites in 28 countries. RESULTS: IVC thrombosis patients were younger (51.9 vs. 59.8 years), more frequently had active cancer (26.0% vs. 8.9%) or history of cancer (21.0% vs. 12.2%), and less frequently had recent trauma or surgery than LEDVT patients. IVC thrombosis was more frequently treated with parenteral anticoagulants alone (35.1% vs. 15.9%), whereas patients with LEDVT more commonly received vitamin K antagonists (32.0% vs. 25.8%) or direct oral anticoagulants (49.0% vs. 35.1%). Thrombolysis (11.0% vs. 3.6%) and surgical/mechanical interventions (4.0% vs. 1.4%) were more frequent in IVC thrombosis. At 24‐months, the rate per 100 person‐years (95% confidence interval) of all‐cause mortality was higher in patients with IVC thrombosis than LEDVT (13.28 [8.57–20.58] vs. 4.91 [4.55–5.3]); the incidence of cancer‐associated mortality was comparable as was the incidence of VTE recurrence (4.11 [1.85–9.15] vs. 4.18 [3.84–4.55]). Major bleeding was slightly higher in IVC thrombosis (2.03 [0.66–6.31] vs. 1.66 [1.45–1.89]). CONCLUSION: In summary, IVC thrombosis patients have higher all‐cause mortality rates than those with LEDVT, a finding only partly attributable to malignancy

The influence of anemia on clinical outcomes in venous thromboembolism: Results from GARFIELD-VTE

Introduction: Clinical characteristics and outcomes of venous thromboembolism (VTE) patients with concomitant anemia are unclear. This study compares baseline characteristics, treatment patterns, and 24-month outcomes in patients with and without anemia within GARFIELD-VTE. Materials and methods: GARFIELD-VTE (ClinicalTrials.gov: NCT02155491) is a global, prospective, non-interventional registry of real-world treatment practices. Of the 10,679 patients enrolled in GARFIELD-VTE, 7698 were eligible for analysis. Primary outcomes were all-cause mortality, recurrent VTE, and major bleeding in VTE patients with or without concomitant anemia over 24-months after diagnosis. Event rates and 95% confidence intervals were estimated using Poisson regression. Adjusted hazard ratios were calculated using Cox proportional hazard models. Results: Distribution of VTE events in 2771 patients with anemia and 4927 without anemia was similar (deep-vein thrombosis alone: 61·1% vs. 55·9%, pulmonary embolism ± deep vein thrombosis: 38·9% vs. 44·0%, respectively). Patients with anemia were older (62.6 year vs. 58.9 years) than those without. At baseline, VTE risk factors that were more common in patients with anemia included hospitalization (22·0% vs. 6·8%), surgery (19·2% vs. 8·2%), cancer (20·1% vs. 5·6%) and acute medical illness (8·3% vs. 4·2%). Patients with anemia were more likely to receive parenteral anticoagulation therapy alone than those without anemia (26·6% vs. 11·7%) and less likely to receive a direct oral anticoagulant (38·5% vs. 53·5%). During 24-months of follow-up, patients with anemia had a higher risk (adjusted hazard ratio [95% confidence interval]) of all-cause mortality (1·84 [1·56-2·18]), major bleeding (2·83 [2·14-3·75]). Among anemia patients, the risk of all-cause mortality and major bleeding remained higher in patients with severe anemia than in those with mild/moderate anemia, all-cause mortality: HR 1·43 [95% CI: 1·21-1·77]; major bleeding: HR 2·08 [95% CI: 1·52-2·86]). Conclusions: VTE patients with concomitant anemia have a higher risk of adverse clinical outcomes compared with those without anemia. Further optimization of anticoagulation therapy for VTE patients with anemia is warranted.</p

Characteristics and Management of Patients with Venous Thromboembolism: The GARFIELD-VTE Registry

Management of venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), varies worldwide

Characteristics and Management of Patients with Venous Thromboembolism: The GARFIELD-VTE Registry

BACKGROUND:  Management of venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), varies worldwide. METHODS:  The Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE) is a prospective, observational study of 10,685 patients with objectively diagnosed VTE recruited from May 2014 to January 2017 at 417 sites in 28 countries. All patients are followed for at least 3 years. We describe the baseline characteristics of the study population and their management within 30 days of diagnosis. RESULTS:  The median age was 60.2 years; 50.4% were male; 61.7% had DVT and 38.3% had PE ± DVT; and 32.3% were obese (body mass index ≥ 30 kg/m2). The most common risk factors were surgery (12.5%), hospitalization (12.0%) and trauma to the lower limbs (7.8%). At the time of VTE diagnosis, 10.1% had active cancer and 5.7% were chronically immobilized. Treatment for VTE was anticoagulant (AC) therapy alone in 90.9% of patients; 5.1% received thrombolytic and/or surgical/mechanical therapy ± AC and 4.0% received no therapy. Pre-diagnosis, 12.8% received AC therapy alone and 0.2% received thrombolytic and/or surgical/mechanical therapy ± AC. After diagnosis, parenteral AC therapy alone was administered in 17.6% of patients, and it was followed by a direct oral AC (DOAC) in 16.4% or a vitamin K antagonist (VKA) in 26.8%. DOACs alone were prescribed to 32.3% of patients, while 5.9% received VKA alone. CONCLUSION:  The initial findings from this global registry highlight the heterogeneity in characteristics and management of VTE patients. Prospective follow-up will reveal the impact of this heterogeneity on outcomes.status: publishe

Influence of body mass index on clinical outcomes in venous thromboembolism: Insights from GARFIELD-VTE

Background: There is limited information on the influence of body mass index (BMI) on clinical outcomes in patients with venous thromboembolism (VTE). Objectives: Investigate the influence of BMI on baseline characteristics, treatment patterns, and 24-month outcomes in VTE patients. Methods: GARFIELD-VTE is a prospective, non-interventional study of 10 869 patients with objectively confirmed VTE. Patients were grouped according to BMI: &lt;18.5 (underweight; n = 214); 18.5-24.9 (normal; n = 2866); 25.0-29.9 (overweight; n = 3326); ≥30 (obese; n = 3073). Results: Compared with patients with a normal BMI, obese patients were more frequently Caucasian (77.4% vs. 57.9%), treated in the outpatient setting (30.4% vs. 23.1%), and had previous VTE (17.5% vs. 11.7%). Active cancer was associated with lower BMI (underweight: 30.4%, normal: 13.5%, overweight: 9.4%, obese: 7.0%). At baseline, overweight and obese patients less often received parenteral therapy alone (16.7% and 14.4%) compared with those with an underweight or normal BMI (30.8% and 21.6%). Obese patients more commonly remained on anticoagulants for ≥2-years compared to those with a normal BMI (52.3% vs. 37.7%). After 24-months, the risk of all-cause mortality was lower in overweight and obese patients than in those with normal BMI (adjusted hazard ratio [95% CI]; 0.75 [0.63-0.89] and 0.59 [0.49-0.72], respectively). Underweight patients more often experienced major bleeding (2.45 [1.41-4.26]) and all-cause mortality (1.90 [1.43-2.53]) than patients with a normal BMI. Recurrent VTE was comparable among groups. Conclusion: Underweight VTE patients have the highest risk of mortality and major bleeding. The risk of mortality in obese VTE patients is lower than that in VTE patients with a normal BMI.</p

On-treatment Comparative Effectiveness of Vitamin K Antagonists and Direct Oral Anticoagulants in GARFIELD-VTE, and Focus on Cancer and Renal Disease

Background  Direct oral anticoagulants (DOACs) provide a safe, effective alternative to vitamin K antagonists (VKAs) for venous thromboembolism (VTE) treatment, as shown via intention-to-treat comparative effectiveness analysis. However, on-treatment analysis is imperative in observational studies because anticoagulation choice and duration are at investigators' discretion. Objectives  The aim of the study is to compare the effectiveness of DOACs and VKAs on 12-month outcomes in VTE patients using on-treatment analysis. Methods  The Global Anticoagulant Registry in the FIELD - VTE (GARFIELD-VTE) is a world-wide, prospective, non-interventional study observing treatment of VTE in routine clinical practice. Results  In total, 8,034 patients received VKAs ( n  = 3,043, 37.9%) or DOACs ( n  = 4,991, 62.1%). After adjustment for baseline characteristics and follow-up bleeding events, and accounting for possible time-varying confounding, all-cause mortality was significantly lower with DOACs than VKAs (hazard ratio: 0.58 [95% confidence interval 0.42-0.79]). Furthermore, patients receiving VKAs were more likely to die of VTE complications (4.9 vs. 2.2%) or bleeding (4.9 vs. 0.0%). There was no significant difference in rates of recurrent VTE (hazard ratio: 0.74 [0.55-1.01]), major bleeding (hazard ratio: 0.76 [0.47-1.24]), or overall bleeding (hazard ratio: 0.87 [0.72-1.05]) with DOACs or VKAs. Unadjusted analyses suggested that VKA patients with active cancer or renal insufficiency were more likely to die than patients treated with DOAC (52.51 [37.33-73.86] vs. 26.52 [19.37-36.29] and 9.97 [7.51-13.23] vs. 4.70 [3.25-6.81] per 100 person-years, respectively). Conclusion  DOACs and VKAs had similar rates of recurrent VTE and major bleeding. However, DOACs were associated with reduced all-cause mortality and a lower likelihood of death from VTE or bleeding compared with VKAs