scholarly journals Extended-Duration Low-intensity Apixaban to Prevent Recurrence in Patients with Provoked Venous Thromboembolism: Design of the HI-PRO Trial

2021 ◽  
Author(s):  
Behnood Bikdeli ◽  
Heather Hogan ◽  
Ruth Morrison ◽  
John Fanikos ◽  
Umberto Campia ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Standard Dose ◽  
Major Surgery ◽  
Duration Of Treatment ◽  
Double Blind ◽  
Safety Outcome ◽  
Low Intensity ◽  
Peripheral Ischemia ◽  
Extended Duration

Patients with acute venous thromboembolism (VTE) in the setting of transient provoking factors are typically treated with short-term anticoagulation. However, the risk of recurrence may be increased in the presence of enduring risk factors. In such patients, the optimal duration of treatment remains uncertain. HI-PRO is a single-center, double-blind randomized trial. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) following a major provoking factor, including major surgery or major trauma, who completed at least 3 months of standard-dose therapeutic anticoagulation and have at least one enduring risk factor (such as obesity or heart failure), will be considered for inclusion. Patients will be randomized to apixaban 2.5 mg twice daily or placebo for 12 months. The primary efficacy outcome will be symptomatic recurrent VTE –a composite of DVT and/or PE at 12 months after randomization. Secondary efficacy outcomes include a composite of death due to cardiovascular causes, nonfatal myocardial infarction, stroke or systemic embolism, major adverse limb events, or coronary or peripheral ischemia requiring revascularization at 12 months, and individual components of these outcomes. The primary safety outcome is major bleeding according to the International Society on Thrombosis and Haemostasis definition. The study plans to enroll 600 patients (300 per arm) to have 80% power for detecting a 75% relative risk reduction in the primary outcome. Active recruitment began in March 2021. HI-PRO will provide clinically meaningful data on whether patients with provoked VTE and enduring risk factors have fewer adverse clinical outcomes if prescribed low-intensity extended duration anticoagulation.

P3850Impact of sex and risk factors for venous thromboembolism on the clinical course of first acute venous thromboembolism. Insights from the PREFER in VTE

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Giustozzi ◽  
S Barco ◽  
L Valerio ◽  
F A Klok ◽  
M C Vedovati ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Baseline Risk ◽  
Major Surgery ◽  
First Episode ◽  
Risk Of Recurrence ◽  
Recurrent Vte ◽  
The Impact

Abstract Introduction The interaction between sex and specific provoking risk factors for venous thromboembolism (VTE) may influence initial presentation and prognosis. Purpose We investigated the impact of sex on the risk of recurrence across subgroups of patients with first VTE classified according to baseline risk factors. Methods PREFER in VTE was an international, non-interventional registry (2013–2015) including patients with a first episode of acute symptomatic objectively diagnosed VTE. We studied the risk of recurrence in patients classified according to baseline provoking risk factors for VTE consisted of i) major transient (major surgery/trauma, >5 days in bed), ii) minor transient (pregnancy or puerperium, estroprogestinic therapy, prolonged immobilization, current infection or bone fracture/soft tissue trauma); iii) unprovoked events, iv) active cancer-associated VTE. Results A total of 3,455 patients diagnosed with first acute VTE were identified, of whom 1,623 (47%) were women. The percentage of patients with a major transient risk factor was 22.2% among women and 19.7% among men. Minor transient risk factors were present in 21.3% and 12.4%, unprovoked VTE in 51.6% and 61.6%, cancer-associated VTE in 4.9% of women and 6.3% of men, respectively. The proportions of cases treated with Vitamin-K antagonists (VKAs) and direct oral anticoagulants (DOACs) were similar between sexes. Median length of treatment of VKAs was 181.5 and 182.0 days and of DOACs was 113.0 and 155.0 days in women and men, respectively. At 12-months of follow-up, VTE recurrence was reported in 74 (4.8%) women and 80 (4.5%) men. Table 1 shows the sex-specific proportion of recurrences by VTE risk factor categories. Table 1 Major Transient (n=722) Minor transient (n=573) Cancer-associated (n=195) Unprovoked (1965) Women (361) Men (361) OR (95% CI) Women (346) Men (227) OR (95% CI) Women (79) Men (116) OR (95% CI) Women (837) Men (1128) OR (95% CI) One-year follow-up, n (N%)   Recurrent VTE, 21 (6.2) 10 (2.9) 0.46 (0.2; 0.9) 9 (2.7) 12 (5.4) 2.09 (0.9; 5.0) 6 (8.0) 5 (4.5) 0.54 (0.2; 1.9) 38 (4.7) 53 (4.7) 1.03 (0.7; 1.6)   Major bleeding, 6 (1.8) 5 (1.5) 0.83 (0.3; 2.7) 5 (1.5) 1 (0.5) 0.30 (0.1; 2.6) 1 (1.3) 3 (2.7) 2.07 (0.2; 20) 10 (1.2) 15 (1.4) 1.11 (0.6; 2.4)   All-cause death, 37 (10.2) 31 (8.5) 0.82 (0.5; 1.4) 10 (2.9) 14 (6.2) 2.21 (0.9; 5.1) 26 (32.9) 49 (42.2) 1.49 (0.8; 2.7) 33 (3.9) 30 (2.7) 0.66 (0.4; 1.1) Conclusions The proportion of patients with recurrent VTE events after first acute symptomatic VTE provoked by transient risk factors was not negligible during the first year of follow-up during in both women and men. These results may have implications on the decision whether to consider extended anticoagulant therapy in selected patients with provoked events. Acknowledgement/Funding This study was funded by Daiichi Sankyo.

Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism

2015 ◽  
Vol 114 (09) ◽  
pp. 645-650 ◽  
Author(s):  
Rupert Bauersachs ◽  
Jan Beyer-Westendorf ◽  
Henri Bounameaux ◽  
Timothy Brighton ◽  
Alexander Cohen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Anticoagulant Therapy ◽  
Low Dose ◽  
Double Blind ◽  
Once Daily ◽  
Safety Outcome ◽  
Dose Aspirin ◽  
Recurrent Venous Thromboembolism ◽  
Low Dose Aspirin ◽  
Recurrent Vte

SummaryPatients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6–12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE): Venous Thromboembolism Prophylaxis Practices in Acutely Ill Medical Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1762-1762 ◽  
Author(s):  
Victor F. Tapson ◽  
Herve Decousus ◽  
Jean-Fran[ccedi]ois Bergmann ◽  
Beng H. Chong ◽  
James B. Froehlich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Major Surgery ◽  
Medical Illness ◽  
Medical Patients ◽  
Median Length ◽  
Thromboembolism Prophylaxis ◽  
Vte Prophylaxis ◽  
Elastic Stockings

Abstract Background Despite consensus group recommendations indicating that medical patients should receive appropriate venous thromboembolism (VTE) prophylaxis, prophylaxis practices remain poorly characterized. This analysis of IMPROVE, a prospective study of acutely ill medical patients, describes in-hospital prophylaxis practices prior to the publication of updated VTE prevention guidelines by the American College of Chest Physicians. Methods Patient recruitment began in July 2002. Patients ≥18 years old, and hospitalized for ≥3 days with an acute medical illness are enrolled consecutively. Exclusion criteria are: therapeutic antithrombotics/thrombolytics at admission; major surgery or trauma during 3 months prior to admission; and VTE treatment begun within 24 hours of admission. Results Data were from 4315 patients (32% from USA) enrolled up to 30 June 2004 in 37 hospitals in 11 countries (76% with 3-month follow-up data). Patients are 50% female, median (IQR) age 69 (50–80) years, median length of hospital stay 8 (5–14) days, median weight 68 (58–80) kg, and 40% were immobile for ≥3 days (median length of immobility 7 [4–14] days, including immobility immediately prior to admission). In-hospital VTE prophylaxis was received by 41% of patients (Table 1). Of patients with no risk factors (44%), one risk factor (40%), or ≥2 risk factors (16%), 25%, 49%, and 67% received prophylaxis, respectively. 12% of IMPROVE patients would have been eligible for inclusion in the MEDENOX study. Of these, only 52% received prophylaxis in hospital. Prophylaxis was provided to 6% of patients during the 3-month follow-up period, and continued in 11% of patients after discharge. Conclusions Only 41% of IMPROVE patients received VTE prophylaxis, with considerable variation in types and regimens of prophylaxis used. While MEDENOX showed the benefits of VTE prophylaxis (enoxaparin 40 mg) in acutely ill medical patients, only half of MEDENOX-eligible patients received prophylaxis. Table 1. Use of in-hospital VTE prophylaxis (N=4315) VTE prophylaxis Patients receiving VTE prophylaxis, % ROW, rest of world; *Excluding elastic stockings and aspirin ≥1 type of VTE prophylaxis* 41 LMWH - USA (Q12h, Qd) 7 (5, 1) LMWH- ROW (Q12h, Qd) 31 (29, 2) UFH - USA (Q12h, Q8h) 28 (15, 11) UFH - ROW (Q12h, Q8h) 6 (5, 0) Intermittent pneumatic compression (USA, ROW) 6 (19, 0) Aspirin (USA, ROW) 4 (7, 3) Elastic stockings (USA, ROW) 6 (3, 8)

scholarly journals Characteristics and Outcomes in Patients with Venous Thromboembolism Taking Concomitant Anti-Platelet Agents and Anticoagulants in the AMPLIFY Trial

2019 ◽  
Vol 119 (03) ◽  
pp. 461-466 ◽  
Author(s):  
Alexander Cohen ◽  
Giancarlo Agnelli ◽  
Harry Buller ◽  
Alexander Gallus ◽  
Gary Raskob ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Conventional Therapy ◽  
International Normalized Ratio ◽  
P Value ◽  
Double Blind ◽  
Safety Outcome ◽  
Anti Platelet Therapy ◽  
Efficacy Outcome ◽  
Acute Venous Thromboembolism

AbstractThe double-blind, randomized, AMPLIFY trial compared 6 months' treatment with apixaban (10 mg twice daily for 7 days and 5 mg twice daily thereafter) versus conventional treatment (subcutaneous enoxaparin [1 mg/kg twice daily for ≥ 5 days] overlapped and followed by warfarin [international normalized ratio = 2.0–3.0]) in patients with acute venous thromboembolism (VTE). This post hoc analysis of AMPLIFY compared outcomes among those taking or not taking concomitant anti-platelet therapy. The primary efficacy outcome was recurrent VTE or VTE-related death; the principal safety outcome was major bleeding. Of 5,365 (apixaban, n = 2,676; enoxaparin/warfarin, n = 2,689) randomized patients, 813 (apixaban, n = 402 [15%]; enoxaparin/warfarin, n = 411 [15%]) took concomitant anti-platelet therapy, of which 92% consisted of low-dose aspirin. Rates of VTE or VTE-related death were similar whether or not anti-platelet agents were taken (apixaban: 3.6 and 2.0%; enoxaparin/warfarin: 3.0 and 2.6%; anti-platelet use: relative risk [RR], 1.23; 95% confidence interval [CI], 0.58–2.62; no anti-platelet use: RR, 0.77; 95% CI, 0.52–1.13); interaction p-value = 0.299. Major bleeding rates were threefold higher in those taking versus those not taking anti-platelet agents (apixaban: 1.2 and 0.4%; enoxaparin/warfarin: 4.1 and 1.4%; anti-platelet use: RR, 0.30; 95% CI, 0.11–0.81; no anti-platelet use: RR, 0.31; 95% CI, 0.15–0.63); interaction p-value = 0.924. Concomitant anti-platelet therapy produced a proportionally similar increase in major bleeding in patients randomized to apixaban or conventional therapy, but there were fewer major bleeds with apixaban. Therefore, the overall safety of apixaban over conventional therapy was maintained in patients receiving anti-platelet therapy. Clinicaltrials.gov: NCT00643201.

Extended-Duration Enoxaparin for Venous Thromboembolism Prophylaxis in Acutely Ill Medical Patients: An Evaluation of the EXCLAIM Study Based on a Recently Recommended Composite Efficacy Endpoint.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1870-1870 ◽  
Author(s):  
Sebastian M. Schellong ◽  
Russell D. Hull ◽  
Victor F. Tapson ◽  
Manuel Monreal ◽  
Meyer-Michel Samama ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Composite Endpoint ◽  
Medical Patients ◽  
Double Blind ◽  
Once Daily ◽  
All Cause Mortality ◽  
Standard Duration ◽  
Extended Duration ◽  
Level 1 ◽  
Reduced Mobility

Abstract Introduction The EXCLAIM study has shown that in acutely ill medical patients who have received a standard 10-day period of prophylaxis with enoxaparin, extended-duration prophylaxis with enoxaparin for 4 weeks reduces the relative risk of the primary composite endpoint of asymptomatic proximal deep-vein thrombosis (DVT), symptomatic DVT or pulmonary embolism (PE), and fatal PE by 44% compared with placebo (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.0011). We assessed the consistency of these results using the composite efficacy endpoint recently proposed for venous thromboembolism (VTE) prophylaxis studies by the European Committee for Medicinal Products for Human Use (CHMP) which, in addition, takes all-cause mortality into account. Methods Patients enrolled in the EXCLAIM study had a recent reduced mobility (≤3 days) due to a medical illness, were aged 40 years or older, and had anticipated level 1 (total bed rest or sedentary without bathroom privileges) or level 2 (level 1 with bathroom privileges) reduced mobility with further risk factors. Eligible patients received enoxaparin 40mg SC once-daily for 10±4 days. Patients were then double-blind randomized and received either enoxaparin 40mg SC once-daily or placebo for a further 28±4 days. Asymptomatic DVT were diagnosed by bilateral compression ultrasound after completion of the randomized treatment period. Suspected cases of symptomatic DVT or PE were confirmed by objective tests. Fatal PE were confirmed by autopsy where possible. Data were analyzed using the CHMP-recommended composite efficacy endpoint of proximal DVT, adjudicated PE and all-cause mortality. Results Eligible patients enrolled at 370 sites in 20 countries received standard-duration prophylaxis with enoxaparin. Of these, 4114 patients were double-blind randomized and 4040 received extended-duration prophylaxis with enoxaparin (n=2013) and placebo (n=2027), respectively. Extended-duration enoxaparin reduced the relative risk of the CHMP composite endpoint by 26% compared with placebo (5.8% vs 7.9%; RR 0.74; 95% CI 0.58–0.95; p=0.018). Conclusion The significant reduction in the incidence of the primary efficacy endpoint associated with the use of extended-duration enoxaparin compared with placebo, following standard duration enoxaparin, was consistent when applying both the pre-defined EXCLAIM and the CHMP-recommended composite endpoints, the latter of which included all-cause mortality in addition to proximal DVT and adjudicated PE.

scholarly journals Venous Thromboembolism Risk in Head and Neck Cancer: Significance of the Preoperative Platelet-to-Lymphocyte Ratio

2017 ◽  
Author(s):  
Tristan Tham ◽  
Lauren Rahman ◽  
Christina Persaud ◽  
Peter Costantino
Keyword(s):  
Risk Factors ◽  
Head And Neck Cancer ◽  
Venous Thromboembolism ◽  
Head And Neck ◽  
Neck Cancer ◽  
Oral Presentation ◽  
Univariate Analysis ◽  
Major Surgery ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio

Abstract (250 limit)ObjectiveWe aimed to investigate the association between the preoperative platelet-to-lymphocyte ratio (PLR) and venous thromboembolism (VTE) in head and neck cancer (HNC) patients undergoing major surgery.Study DesignRetrospective cohort studySettingAcademic tertiary hospital from 2011 to 2017Subjects and MethodsPatients with confirmed HNC undergoing major surgery were included in this study. The preoperative PLR was recorded for all patients. Known VTE risk factors, including age, sex, smoking, BMI, prior VTE, and anticoagulation were also recorded. Risk factors were screened in univariate analysis using Wilcoxon’s rank sum test and χ2 test (Bonferroni corrected). Significant covariates were subsequently included in a multivariate regression model. Bootstrap techniques were used to obtain credible confidence intervals (CI).ResultsThere were 306 patients enrolled with 7 cases of VTE (6 DVTs and 1 PE). On univariate analysis, length of stay (p = 0.0026), length of surgery (p = 0.0029), and PLR (p = 0.0002) were founded to have significant associations with VTE. A Receiver Operator Characteristic (ROC) curve was constructed, that yielded an AUROC of 0.905 (95% CI: 0.82 - 0.98). Using an optimized cutoff, the multivariate model showed that length of surgery (β 95% CI: 0.0001 - 0.0006; p = 0.0056), and PLR (β 95% CI: 5.3256 - 5.3868; p < 0.0001) were significant independent predictors of VTE.ConclusionThis exploratory pilot study has shown that PLR offers a potentially accurate risk stratification measure as an adjunct to current tools in VTE risk prediction, without additional cost to health systems.Oral PresentationThis data was presented as an oral presentation at the Annual American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNSF) Meeting, 13th September 2017

scholarly journals Hypercoagulable States and Thrombophilias: Risks Relating to Recurrent Venous Thromboembolism

2018 ◽  
Vol 35 (02) ◽  
pp. 99-104 ◽  
Author(s):  
Marissa Rybstein ◽  
Maria DeSancho
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Previous History ◽  
Anticoagulation Therapy ◽  
Individual Risk ◽  
Major Surgery ◽  
Factors Affecting ◽  
Recurrent Vte ◽  
Active Cancer

AbstractInherited and acquired thrombophilias and hypercoagulable states, such as active cancer, estrogen-induced, autoimmune disorders, major surgery, hospitalization, and trauma, are well-known risk factors for venous thromboembolism (VTE). The effect of these on recurrent VTE is different for each specific risk factor. The major risk factors affecting VTE recurrence include the presence of active cancer and an unprovoked first VTE. In addition, the use of combined female hormones in a woman with a previous history of estrogen-related VTE is a major risk factor for VTE recurrence. The extent of influence of inherited thrombophilia on the risk of recurrence is controversial. Conversely, the presence of antiphospholipid antibodies, specifically triple positive carriers, appears to increase the risk of VTE recurrence. Understanding the rates of recurrent VTE in a patient and the individual risk of bleeding is important in determining the duration of anticoagulation therapy.

scholarly journals A Review of Warfarin Dosing and Monitoring

2018 ◽  
Vol 13 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Khan Md Arif ◽  
Mohammad Ashiqur Rahman
Keyword(s):  
Venous Thromboembolism ◽  
Heart Valves ◽  
Warfarin Therapy ◽  
Thrombus Formation ◽  
Therapeutic Index ◽  
International Normalized Ratio ◽  
Major Surgery ◽  
Clotting Factors ◽  
Duration Of Treatment ◽  
Oral Anticoagulant Treatment

The anticoagulant drug warfarin is a vitamin K antagonist, coumarin derivative which inhibits the synthesis of clotting factors II, VII, IX, and X, as well as the naturally occurring endogenous anticoagulant proteins C and S. Warfarin is still considered the mainstay of oral anticoagulant treatment, it is a difficult drug to manage due to its narrow therapeutic index. An inappropriate management of patients can lead to subtherapeutic or supratherapeutic levels, increasing the risk of thromboembolic episodes or hemorrhagic episodes, respectively. Common indications for the use of warfarin include stroke prevention in atrial fibrillation, preventing thrombus formation in patients with heart valves and treatment of venous thromboembolism. When warfarin therapy is initiated for venous thromboembolism, it should be given the first day, along with a heparin product or fondaparinux. The heparin product or fondaparinux should be continued for at least five days and until the patient's international normalized ratio is at least 2.0 for two consecutive days. The international normalized ratio goal and duration of treatment with warfarin vary depending on indication and risk. Warfarin therapy should be stopped five days before major surgery and restarted 12 to 24 hours postoperatively. Bridging with low-molecular-weight heparin or other agents is based on balancing the risk of throm boembolism with the risk of bleeding.Faridpur Med. Coll. J. Jan 2018;13(1): 40-43

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