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.
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.
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).
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.
•GARFIELD-VTE compared 24-month outcomes in VTE patients with and without anemia•VTE patients with anemia were less likely to received DOACs than those without anemia•VTE patients with anemia had a higher risk of all-cause mortality and major bleeding•Severe anemia was associated with a higher outcome risks than mild/moderate anemia
Many patients with atrial fibrillation suffer from comorbid vascular disease. The comparative efficacy and safety of different types of oral anticoagulation (OAC) in this patient group have not been ...widely studied.
Adults with newly-diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed for 24 months. Associations of vascular disease with clinical outcomes were analysed using adjusted hazard ratios (HR), obtained via Cox proportional-hazard modelling. Outcomes of OAC vs no OAC, and of non-vitamin K antagonist OAC (NOAC) vs vitamin K antagonist (VKA) treatment, were compared by overlap propensity weighted Cox proportional-hazard models.
Of 51,574 atrial fibrillation patients, 25.9% had vascular disease. Among eligible atrial fibrillation patients, those with vascular disease received OAC less frequently than those without (63% vs 73%). Over 2-years follow-up, patients with vascular disease showed a higher risk of all-cause mortality (HR 95% CI: 1.30 1.16-1.47) and cardiovascular mortality (1.59 1.28-1.97). OAC was associated with a significant decrease in all-cause mortality and non-haemorrhagic stroke, and increased risk of major bleeding in non-vascular disease. In vascular disease, similar but non-significant trends existed for stroke and major bleeding. A significantly lower risk of all-cause mortality (0.74 0.61-0.90) and major bleeding (0.45 0.29-0.70) was observed in vascular disease patients treated with NOACs compared to VKAs.
Atrial fibrillation patients with a history of vascular disease have worse long-term outcomes than those without. The association of NOACs vs VKA with clinical outcomes was more evident in atrial fibrillation patients with vascular disease.
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Aims
This study aims to describe both management and prognosis of patients with diabetes mellitus (DM) and newly diagnosed atrial fibrillation (AF), overall as well as by antidiabetic treatment, and ...to assess the influence of oral anticoagulation (OAC) on outcomes by DM status.
Methods
The study population comprised 52 010 newly diagnosed patients with AF, 11 542 DM and 40 468 non‐DM, enrolled in the GARFIELD‐AF registry. Follow‐up was truncated at 2 years after enrolment. Comparative effectiveness of OAC versus no OAC was assessed by DM status using a propensity score overlap weighting scheme and weights were applied to Cox models.
Results
Patients with DM 39.3% oral antidiabetic drug (OAD), 13.4% insulin ± OAD, 47.2% on no antidiabetic drug had higher risk profile, OAC use, and rates of clinical outcomes compared with patients without DM. OAC use was associated in patients without DM and patients with DM with lower risk of all‐cause mortality hazard ratio 0.75 (0.69‐0.83), 0.74 (0.64‐0.86), respectively and stroke/systemic embolism (SE) 0.69 (0.58‐0.83), 0.70 (0.53‐0.93), respectively. The risk of major bleeding with OAC was similarly increased in patients without DM and those with DM 1.40 (1.14‐1.71), 1.37 (0.99‐1.89), respectively. Patients with insulin‐requiring DM had a higher risk of all‐cause mortality and stroke/SE 1.91 (1.63‐2.24), 1.57 (1.06‐2.35), respectively compared with patients without DM, and experienced significant risk reductions of all‐cause mortality and stroke/SE with OAC 0.73 (0.53‐0.99); 0.50 (0.26‐0.97), respectively.
Conclusions
In both patients with DM and patients without DM with AF, OAC was associated with lower risk of all‐cause mortality and stroke/SE. Patients with insulin‐requiring DM derived significant benefit from OAC.
Abstract
Aims
Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. ...The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation.
Methods and results
Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48–0.71 (recurrence) and 0.61–0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% –19% for bleeding.
Conclusion
The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making.
Structured Graphical Abstract
Structured Graphical Abstract
BMI, body mass index; DOAC, direct oral anticoagulant; DVT, deep venous thrombosis; Hb, haemoglobin; SBP, systolic blood pressure; VKA, vitamin K antagonist; VTE, venous thromboembolism.
Abstract
Cancer-associated thrombosis, with the incidence rising over the years, is associated with significant morbidity and mortality in patients with cancer. Recent advances in the treatment of ...cancer-associated venous thromboembolism (VTE) include the introduction of direct oral anticoagulants (DOACs), which provide a more convenient and effective option than low-molecular-weight heparin (LMWH). Nonetheless, important unmet needs remain including an increased risk of bleeding in certain patient subgroups such as those with gastroesophageal cancer, concerns about drug-drug interactions, and management of patients with severe renal impairment. Although DOACs are more convenient than LMWH, persistence can decline over time. Factor XI inhibitors have potential safety advantages over DOACs because factor XI appears to be essential for thrombosis but not hemostasis. In phase II trials, some factor XI inhibitors were superior to enoxaparin for the prevention of VTE after knee replacement surgery without increasing the risk of bleeding. Ongoing trials are assessing the efficacy and safety of factor XI inhibitors for the treatment of cancer-associated VTE.
This narrative review summarizes advances in the treatment of cancer-associated venous thromboembolism, outlines key unmet needs with the current treatment, and discusses how factor XI inhibitors may address the current knowledge gaps.
Rivaroxaban (BAY 59-7939)--an oral, direct Factor Xa inhibitor--could be an alternative to heparins and warfarin for the prevention and treatment of thromboembolic disorders.
This randomized, ...double-blind, double-dummy, active-comparator-controlled, multinational, dose-ranging study assessed the efficacy and safety of once-daily rivaroxaban relative to enoxaparin for prevention of venous thromboembolism in patients undergoing elective total hip replacement. Patients (n=873) were randomized to once-daily oral rivaroxaban doses of 5, 10, 20, 30, or 40 mg (initiated 6 to 8 hours after surgery) or a once-daily subcutaneous enoxaparin dose of 40 mg (given the evening before and > or = 6 hours after surgery). Study drugs were continued for an additional 5 to 9 days; mandatory bilateral venography was performed the following day. The primary end point (composite of any deep vein thrombosis, objectively confirmed pulmonary embolism, and all-cause mortality) was observed in 14.9%, 10.6%, 8.5%, 13.5%, 6.4%, and 25.2% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=618, per-protocol population). No significant dose-response relationship was found for efficacy (P=0.0852). Major postoperative bleeding was observed in 2.3%, 0.7%, 4.3%, 4.9%, 5.1%, and 1.9% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=845, safety population), representing a significant dose-response relationship (P=0.0391).
Rivaroxaban showed efficacy and safety similar to enoxaparin for thromboprophylaxis after total hip replacement, with the convenience of once-daily oral dosing and without the need for coagulation monitoring. When both efficacy and safety are considered, these results suggest that 10 mg rivaroxaban once daily should be investigated in phase III studies.
Oral anticoagulants (OAC) are underutilized in older patients with atrial fibrillation, despite proven clinical benefits. Our objective was to investigate baseline characteristics, treatment ...patterns, and impact of anticoagulation upon clinical outcomes with respect to age.
Adults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed up for 24 months. Adjusted hazard ratios (HR) were obtained via Cox proportional-hazards models with applied weights, to quantify the association of age with clinical outcomes. Comparative effectiveness of OAC vs No OAC and non-vitamin K oral anticoagulants (NOAC) vs vitamin K antagonists (VKA) were assessed using a propensity score with an overlap weighting scheme.
Of 52,018 patients, 32.6% were 65-74 years of age, 29.3% were 75-84 years, and 7.9% were ≥85 years. OAC treatment was associated with a numerical reduction in all-cause mortality among those aged 65-74 years (HR; 95% confidence interval) (0.86; 0.69-1.06) and aged 75-84 years (0.89; 0.75-1.05) and a significant reduction in patients ≥85 years (0.77; 0.63-0.95) vs no OAC. Similarly, OACs were associated with a decrease in stroke: 65-74 (0.51; 0.35-0.76) and ≥85 years (0.58; 0.34-0.99) and a numerical decrease in 75-84 years (0.84; 0.59-1.18). No increase in major bleeding was observed in patients aged ≥85 treated with OACs. Compared with VKA, NOACs were associated with a significant reduction in all-cause mortality in patients aged <65 and 65-74, with numerical reductions in those aged 75-84 and ≥85 years.
Older patients using OACs saw lower all-cause mortality and stroke risk; NOACs had less mortality and major bleeding compared with VKAs.
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.
Upper extremity deep vein thrombosis (UEDVT) is less common than lower extremity DVT (LEDVT) and consequently less well characterized. This study compared clinical characteristics and 1-year outcomes ...between 438 UEDVT patients and 7,602 LEDVT patients recruited in the GARFIELD-VTE registry. UEDVT patients were significantly more likely to have a central venous catheter than those with LEDVT (11.5% vs. 0.5%;
< 0.0001), and had a higher rate of active cancer (16.2%) or recent hospitalization (19.4%) compared with LEDVT patients (8.7% and 11.2%, respectively). Nearly all patients with UEDVT and LEDVT were initiated on anticoagulant therapy, which was a direct oral anticoagulant in one-third individuals in both groups. At 3, 6, and 12 months, the proportion of UEDVT and LEDVT patients who were receiving anticoagulant therapy was 82.6 and 87.4%, 66.0 and 72.6%, and 45.7 and 54.6%, respectively. In the UEDVT and LEDVT groups, VTE recurrence rate was 4.0 (95% confidence interval CI, 2.4-6.7) and 5.5 (95% CI, 4.9-6.1) per 100 person-years, respectively; major bleed was noted in 1.3 (95% CI, 0.6-3.2) and 1.6 (95% CI, 1.3-1.9) per 100 person-years and all-cause mortality in 9.7 (95% CI, 7.1-13.4) and 6.7 (95% CI, 6.1-7.3) per 100 person-years, respectively. Hence, risk of recurrence was similar in the two groups whereas all-cause mortality was significantly higher in the UEDVT group than the LEDVT group (
= 0.0338). This latter finding was likely due to the high prevalence of cancer in the UEDVT group.
Although epidemiological studies report a lower risk of venous thromboembolism (VTE) than in the Western world, VTE rates in Asia may be underestimated. Furthermore, it is uncertain whether VTE ...outcomes differ in Asia and the rest of the world (ROW).
GARFIELD-VTE is a global, prospective, non-interventional study of real-world treatment practices. In this study, we compared baseline characteristics, treatment patterns, and 12-month outcomes in Asia and ROW.
Of the 10,684 enrolled patients, 1822 (17.1%) were Asian (China n = 420, Hong Kong n = 98, Japan n = 148, Malaysia n = 244, South Korea n = 343, Taiwan n = 232, Thailand n = 337). Compared with ROW patients, those from Asia were more often female (57.4% vs. 48.0%), non-smokers (74.0% vs. 58.9%) and had a lower BMI (24.8 kg/m2 vs. 29.1 kg/m2). Asian patients were more likely to be managed in the hospital (86.9% vs. 70.4%) and to have active cancer (19.8% vs. 8.1%) or a history of cancer (19.1% vs. 12.0%). Asian patients received no anticoagulation more frequently than ROW patients (6.5% vs. 2.1%). Over 12-months follow-up, the rate of all-cause mortality (per 100 person-years 95% confidence interval) was higher in Asians (15.2 13.4–17.3 vs. 5.9 5.4–6.5). Adjusted hazard ratios indicated a higher risk of all-cause mortality in Asian patients than the ROW (1.32 1.08–1.62). The frequencies of major bleeding and recurrent VTE were similar.
Asian patients have different risk profiles, treatment patterns and a higher risk of mortality compared with the ROW.
•GARFIELD-VTE compared VTE practices among Asian and non-Asian patients•Asian patients with VTE were more likely to have active or history of cancer•Asian patients with VTE were less likely to receive anticoagulation therapy•After adjustment, the risk of mortality was higher in Asians than non-Asians
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