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Chest Mar 2022Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE.
RESEARCH QUESTION
Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE?
STUDY DESIGN AND METHODS
In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months.
RESULTS
Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97).
INTERPRETATION
In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT02746185; URL: www.
CLINICALTRIALS
gov.
Topics: Aged; Anticoagulants; Dalteparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism
PubMed: 34627853
DOI: 10.1016/j.chest.2021.09.037 -
The New England Journal of Medicine Apr 2020Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use.
METHODS
This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding.
RESULTS
Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60).
CONCLUSIONS
Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).
Topics: Administration, Oral; Aged; Anticoagulants; Dalteparin; Female; Hemorrhage; Humans; Incidence; Injections, Subcutaneous; Intention to Treat Analysis; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Pulmonary Embolism; Pyrazoles; Pyridones; Secondary Prevention; Single-Blind Method; Venous Thromboembolism; Venous Thrombosis
PubMed: 32223112
DOI: 10.1056/NEJMoa1915103 -
Journal of Thrombosis and Haemostasis :... Feb 2020Low-molecular-weight heparin is the guideline-endorsed treatment for cancer-associated venous thromboembolism (VTE). While apixaban is approved for the treatment of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Low-molecular-weight heparin is the guideline-endorsed treatment for cancer-associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, limited data support its use in cancer patients.
OBJECTIVES
The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non-major bleeding (CRNMB).
PATIENTS/METHODS
Patients with cancer-associated VTE were randomly assigned to receive either apixaban 10 mg twice daily for seven days followed by 5 mg twice daily for six months or subcutaneous dalteparin (200 IU/kg for one month followed by 150 IU/kg once daily).
RESULTS
Of 300 patients randomized, 287 were included in the primary analysis. Metastatic disease was present in 66% of subjects; 74% were receiving concurrent chemotherapy. Major bleeding occurred in 0% of 145 patients receiving apixaban, compared with 1.4% of 142 patients receiving dalteparin [P = .138; hazard ratio (HR) not estimable because of 0 bleeding event in apixaban group]. Recurrent VTE occurred in 0.7% of apixaban, compared to 6.3% of dalteparin patients [HR 0.099, 95% confidence interval [CI], 0.013-0.780, P = .0281). Major bleeding or CRNMB rates were 6% for both groups.
CONCLUSIONS
Oral apixaban was associated with low major bleeding and VTE recurrence rates for the treatment of VTE in cancer patients.
Topics: Anticoagulants; Dalteparin; Humans; Neoplasm Recurrence, Local; Pyrazoles; Pyridones; Treatment Outcome; Venous Thromboembolism
PubMed: 31630479
DOI: 10.1111/jth.14662 -
Seminars in Thrombosis and Hemostasis Nov 2020Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching...
Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching epidemic proportions worldwide, the optimal dosage for obese patients has not been established for most anticoagulants, including low-molecular-weight heparin (LMWH), non-vitamin K antagonist oral anticoagulants (NOAC), and pentasaccharides (fondaparinux). The aim of the present systematic review was to summarize the current knowledge and provide recommendations on dosage of LMWH, NOAC, and fondaparinux in obese patients (body mass index [BMI] ≥ 30 kg/m or body weight ≥ 100 kg). Based on a systematic search in PubMed and Embase, a total of 72 studies were identified. For thromboprophylaxis with LMWH in bariatric surgery ( = 20 studies), enoxaparin 40 mg twice daily, dalteparin 5,000 IE twice daily, or tinzaparin 75 IU/kg once daily should be considered for patients with BMI ≥ 40 kg/m. For thromboprophylaxis with LMWH in nonbariatric surgery and in medical inpatients ( = 8 studies), enoxaparin 0.5 mg/kg once or twice daily or tinzaparin 75 IU/kg once daily may be considered in obese patients. For treatment with LMWH ( = 18 studies), a reduced weight-based dose of enoxaparin 0.8 mg/kg twice daily should be considered in patients with BMI ≥ 40 kg/m, and no dose capping of dalteparin and tinzaparin should be applied for body weight < 140 kg. As regards NOAC, rivaroxaban, apixaban, or dabigatran may be used as thromboprophylaxis in patients with BMI < 40 kg/m ( = 4 studies), whereas rivaroxaban and apixaban may be administered to obese patients with VTE or AF, including BMI > 40 kg/m, at standard fixed-dose ( = 20 studies). The limited available evidence on fondaparinux ( = 3 studies) indicated that the treatment dose should be increased to 10 mg once daily in patients weighing > 100 kg.
Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Obesity
PubMed: 33368113
DOI: 10.1055/s-0040-1718405 -
BMJ (Clinical Research Ed.) Jun 2021To determine the efficacy and safety of dalteparin postoperative bridging treatment versus placebo for patients with atrial fibrillation or mechanical heart valves when... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the efficacy and safety of dalteparin postoperative bridging treatment versus placebo for patients with atrial fibrillation or mechanical heart valves when warfarin is temporarily interrupted for a planned procedure.
DESIGN
Prospective, double blind, randomised controlled trial.
SETTING
10 thrombosis research sites in Canada and India between February 2007 and March 2016.
PARTICIPANTS
1471 patients aged 18 years or older with atrial fibrillation or mechanical heart valves who required temporary interruption of warfarin for a procedure.
INTERVENTION
Random assignment to dalteparin (n=821; one patient withdrew consent immediately after randomisation) or placebo (n=650) after the procedure.
MAIN OUTCOME MEASURES
Major thromboembolism (stroke, transient ischaemic attack, proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, peripheral embolism, or vascular death) and major bleeding according to the International Society on Thrombosis and Haemostasis criteria within 90 days of the procedure.
RESULTS
The rate of major thromboembolism within 90 days was 1.2% (eight events in 650 patients) for placebo and 1.0% (eight events in 820 patients) for dalteparin (P=0.64, risk difference -0.3%, 95% confidence interval -1.3 to 0.8). The rate of major bleeding was 2.0% (13 events in 650 patients) for placebo and 1.3% (11 events in 820 patients) for dalteparin (P=0.32, risk difference -0.7, 95% confidence interval -2.0 to 0.7). The results were consistent for the atrial fibrillation and mechanical heart valves groups.
CONCLUSIONS
In patients with atrial fibrillation or mechanical heart valves who had warfarin interrupted for a procedure, no significant benefit was found for postoperative dalteparin bridging to prevent major thromboembolism.
TRIAL REGISTRATION
Clinicaltrials.gov NCT00432796.
Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dalteparin; Double-Blind Method; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Period; Prospective Studies; Surgical Procedures, Operative; Thromboembolism; Warfarin
PubMed: 34108229
DOI: 10.1136/bmj.n1205 -
Taiwanese Journal of Obstetrics &... Mar 2020Due to the morbidity and mortality of mothers and fetuses developed by preeclampsia, preventive approaches have always been taken into account in high risk individuals....
Due to the morbidity and mortality of mothers and fetuses developed by preeclampsia, preventive approaches have always been taken into account in high risk individuals. Systematic review studies contribute to make a better decision about the results of such studies. Accordingly, this study strived to systematically study the factors effective in the prevention of preeclampsia. The MEDLINE, ISI Web of Science, PubMed, Scopus, Google Scholar, and Proquest databases were systematically reviewed between January 2000 and May 2019. The quality of the studies was analyzed using the CONSORT checklist. A study was conducted on 29 quality interventional studies; 28 of which were RCT type, and on various factors such as anticoagulants (heparin, enoxaparin, Dalteparin and Nadroparin), aspirin, paravastatin, nitric oxide, yoga, micronutrients Such as l-Arginine, Folic Acid, Vitamin E and C, Phytonutrient, Lycopene and Vitamin D alone or in combination with Calcium. The results of this study showed that low molecular weight heparin, enoxaparin, PETN, yoga, L arginine, folic acid, vitamin D prevented preeclampsia alone or combined with calcium.
Topics: Arginine; Calcium; Drug Therapy, Combination; Enoxaparin; Female; Folic Acid; Heparin, Low-Molecular-Weight; Humans; Pentaerythritol Tetranitrate; Pre-Eclampsia; Pregnancy; Prenatal Care; Vitamin D; Yoga
PubMed: 32127134
DOI: 10.1016/j.tjog.2020.01.002 -
Allergologie Select 2023Not available.
Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for...
Not available.
PubMed: 37705676
DOI: 10.5414/ALX02422E -
Medical Sciences (Basel, Switzerland) Aug 2023Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis (DVT), poses a significant risk during and after hospitalization, particularly... (Review)
Review
Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis (DVT), poses a significant risk during and after hospitalization, particularly for surgical patients. Among various patient groups, those undergoing major orthopedic surgeries are considered to have a higher susceptibility to PE and DVT. Major lower-extremity orthopedic procedures carry a higher risk of symptomatic VTE compared to most other surgeries, with an estimated incidence of ~4%. The greatest risk period occurs within the first 7-14 days following surgery. Major bleeding is also more prevalent in these surgeries compared to others, with rates estimated between 2% and 4%. For patients undergoing major lower-extremity orthopedic surgery who have a low bleeding risk, it is recommended to use pharmacological thromboprophylaxis with or without mechanical devices. The choice of the initial agent depends on the specific surgery and patient comorbidities. First-line options include low-molecular-weight heparins (LMWHs), direct oral anticoagulants, and aspirin. Second-line options consist of unfractionated heparin (UFH), fondaparinux, and warfarin. For most patients undergoing knee or hip arthroplasty, the initial agents recommended for the early perioperative period are LMWHs (enoxaparin or dalteparin) or direct oral anticoagulants (rivaroxaban or apixaban). In the case of hip fracture surgery, LMWH is recommended as the preferred agent for the entire duration of prophylaxis. However, emerging factor XI(a) inhibitors, as revealed by a recent meta-analysis, have shown a substantial decrease in the occurrence of VTE and bleeding events among patients undergoing major orthopedic surgery. This discovery poses a challenge to the existing paradigm of anticoagulant therapy in this specific patient population and indicates that factor XI(a) inhibitors hold great promise as a potential strategy to be taken into serious consideration.
Topics: Humans; Factor XIa; Anticoagulants; Venous Thromboembolism; Heparin, Low-Molecular-Weight; Heparin; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Pulmonary Embolism
PubMed: 37606428
DOI: 10.3390/medsci11030049 -
Thrombosis and Haemostasis May 2022Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.5%), lung in 200 (17.3%), breast in 155 (13.4%), genitourinary sites in 139 (12%), gynecological sites in 119 (10.3%), and was hematological in 85 patients (7.4%). Rates of VTE recurrence were 10.9% in patients with gynecological, 8.8% with gastrointestinal, 6.5% with genitourinary, and 5.5% with lung cancer with lower rates in the other sites of cancer. Rates of major bleeding were 7.2% in patients with genitourinary and 4.8% with gastrointestinal cancer, with lower rates in patients with other sites of cancer. The observed absolute risk difference in VTE recurrence in favor of apixaban was 11.9% in patients with gynecological, 5.5% with lung, 3.7% with genitourinary cancer, and 0.6% with gastrointestinal cancer. None of the risk differences was statistically significant. The rates of major bleeding in patients treated with apixaban or dalteparin was similar across patients with different cancer sites. In conclusion, recurrences appear to be more common in patients with gastrointestinal and gynecological cancer and major bleedings in patients with genitourinary and gastrointestinal cancer. Oral apixaban is a valid oral alternative to subcutaneous dalteparin for the treatment of a large spectrum of patients with cancer-associated VTE.
Topics: Anticoagulants; Dalteparin; Hemorrhage; Humans; Neoplasms; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 34530482
DOI: 10.1055/s-0041-1735194