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Journal of Gynecologic Oncology Jan 2020Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous... (Comparative Study)
Comparative Study
OBJECTIVES
Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin.
METHODS
The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality.
RESULTS
During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%).
CONCLUSION
In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.
Topics: Aged; Dalteparin; Factor Xa Inhibitors; Female; Genital Neoplasms, Female; Hemorrhage; Humans; Middle Aged; Proportional Hazards Models; Republic of Korea; Rivaroxaban; Venous Thromboembolism
PubMed: 31789000
DOI: 10.3802/jgo.2020.31.e10 -
The European Respiratory Journal Feb 2020In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed to evaluate anticoagulant therapy in cancer patients with incidental and symptomatic VTE.
METHODS
The Hokusai VTE Cancer Study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE. The primary outcome was the composite of first recurrent VTE or major bleeding. Secondary outcomes included major bleeding, recurrent VTE and mortality. Outcomes in patients with incidental and symptomatic VTE were evaluated during the 12-month study period.
RESULTS
331 patients with incidental VTE and 679 patients with symptomatic VTE were enrolled, of whom the index event was confirmed by an independent radiologist. Median durations of anticoagulant treatment were 195 and 189 days, respectively. In patients with incidental VTE, the primary outcome occurred in 12.7% of patients, major bleeding in 6.6% of patients and recurrent VTE in 7.9% of patients. Out of the 26 VTE recurrences in patients with incidental VTE, five (31%) were incidental, seven (44%) were symptomatic and four (25%) were deaths for which pulmonary embolism could not be ruled out. In patients with symptomatic VTE, the primary outcome occurred in 13.8% of patients, major bleeding in 4.9% of patients and recurrent VTE in 10.9% of patients. All-cause mortality was similar in both groups.
CONCLUSION
Clinical adverse outcomes are substantial in both cancer patients with incidental and symptomatic VTE, supporting current guideline recommendations that suggest treating incidental VTE in the same manner as symptomatic VTE.
Topics: Anticoagulants; Dalteparin; Humans; Neoplasm Recurrence, Local; Retrospective Studies; Venous Thromboembolism
PubMed: 31727694
DOI: 10.1183/13993003.01697-2019 -
Open Medicine (Warsaw, Poland) 2020To compare the clinical effectiveness of the two most commonly used LMWHs, dalteparin (DALT) and enoxaparin (ENOX), in thromboprophylaxis of elective total hip...
AIM
To compare the clinical effectiveness of the two most commonly used LMWHs, dalteparin (DALT) and enoxaparin (ENOX), in thromboprophylaxis of elective total hip replacement (THR) or total knee replacement (TKR).
MATERIAL AND METHODS
To the prospective, randomized study were included 66 adult patients qualified to undergo THR or TKR (age 63 ± 12 years, 44 women). The patients were randomized to daily in-hospital subcutaneous prophylaxis with 5,000 I.U. of DALT or 40 mg of enoxaparin. Clinical and laboratory data were collected before surgery, and on 1st and 5th days after surgery.
RESULTS
Thirty-four patients were randomized to prophylaxis with ENOX and 32 with DALT. The groups did not differ significantly in age, sex, creatinine and most of the laboratory parameters. The compared groups had similar surgical parameters, but more patients in the ENOX group received red blood cell infusion (17(50%) vs 8(25%); < 0.05). The Lee-White coagulation time mildly decreased in ENOX and DALT following the surgery ( = ns). There was a shortening of Duke's bleeding time in DALT after the surgery and it became significantly quicker than that in ENOX on Day 5 ( = 0.03).
CONCLUSION
The observed difference in Duke's bleeding time and exceeding blood loss during the surgery on the enoxaparin demands confirmation, as it can be important information for clinical management.
PubMed: 33336060
DOI: 10.1515/med-2020-0213 -
Pediatric Blood & Cancer Dec 2020On May 16, 2019, the U.S. Food and Drug Administration (FDA) approved dalteparin sodium for the treatment of symptomatic venous thromboembolism (VTE) to reduce the risk...
On May 16, 2019, the U.S. Food and Drug Administration (FDA) approved dalteparin sodium for the treatment of symptomatic venous thromboembolism (VTE) to reduce the risk of recurrence in pediatric patients 1 month of age and older. Approval was primarily based on FDA review of a single-arm trial evaluating dalteparin administered subcutaneous twice daily in 38 pediatric patients with symptomatic VTE. Efficacy was based on the achievement of therapeutic plasma anti-Xa levels. The FDA concluded that dalteparin has efficacy and acceptable safety for pediatric patients.
Topics: Adolescent; Adult; Anticoagulants; Child; Child, Preschool; Dalteparin; Drug Approval; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Prognosis; United States; United States Food and Drug Administration; Venous Thromboembolism; Young Adult
PubMed: 32896942
DOI: 10.1002/pbc.28688 -
Journal of Critical Care Dec 2020The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on... (Observational Study)
Observational Study
PURPOSE
The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients.
MATERIAL AND METHODS
We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75-100 IU/kg subcutaneously).
RESULTS
Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity.
CONCLUSIONS
Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.
Topics: Adult; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Critical Illness; Dalteparin; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Risk; Thrombelastography; Venous Thromboembolism; COVID-19 Drug Treatment
PubMed: 32920503
DOI: 10.1016/j.jcrc.2020.08.026 -
World Journal of Surgery Mar 2020In a retrospective cohort study, we looked at the incidence and risk factors of developing in-hospital venous thromboembolism (VTE) after major emergency abdominal...
BACKGROUND
In a retrospective cohort study, we looked at the incidence and risk factors of developing in-hospital venous thromboembolism (VTE) after major emergency abdominal surgery and the risk factors for developing a venous thrombosis.
METHODS
Data were extracted through medical records from all patients undergoing major emergency abdominal surgery at a Danish University Hospital from 2010 until 2016. The primary outcome was the incidence of venous thrombosis developed in the time from surgery until discharge from hospital. The secondary outcomes were 30-day mortality and postoperative complications. Multivariate logistic analyses were used for confounder control.
RESULTS
In total, 1179 patients who underwent major emergency abdominal surgery during 2010-2016 were included. Thirteen patients developed a postoperative venous thromboembolism (1.1%) while hospitalized. Eight patients developed a pulmonary embolism all verified by CT scan and five patients developed a deep venous thrombosis verified by ultrasound scan. Patients diagnosed with a VTE were significantly longer in hospital with a length of stay of 34 versus 14 days, P < 0.001, and they suffered significantly more surgical complications (69.2% vs. 30.4%, P = 0.007). Thirty-day mortality was equal in patients with and without a venous thrombosis. In a multivariate analysis adjusting for gender, ASA group, BMI, type of surgery, dalteparin dose and treatment with anticoagulants, we found that a dalteparin dose ≥5000 IU was associated with the risk of postoperative surgical complications (odds ratio 1.55, 95% CI 1.11-2.16, P = 0.009).
CONCLUSION
In this study, we found a low incidence of venous thrombosis among patients undergoing major emergency abdominal surgery, comparable to the incidence after elective surgery.
Topics: Abdomen; Aged; Emergency Service, Hospital; Female; Humans; Incidence; Logistic Models; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Venous Thromboembolism
PubMed: 31646367
DOI: 10.1007/s00268-019-05246-x -
BMC Medicine Nov 2022The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five...
BACKGROUND
The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs.
METHODS
Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched (Jan-May 2021). The AIM database was screened for all candidates being investigated for pre-eclampsia. Candidates in clinical development were evaluated against nine prespecified criteria from TPPs identified as key for wide-scale implementation, and classified as high, medium or low potential based on matching to the TPPs. Preclinical candidates were categorised by product type, archetype and medicine subclass.
RESULTS
The AIM database identified 153 candidates for pre-eclampsia. Of the 87 candidates in clinical development, seven were classified as high potential (prevention: esomeprazole, L-arginine, chloroquine, vitamin D and metformin; treatment: sulfasalazine and metformin) and eight as medium potential (prevention: probiotic lactobacilli, dalteparin, selenium and omega-3 fatty acid; treatment: sulforaphane, pravastatin, rosuvastatin and vitamin B3). Sixty-six candidates were in preclinical development, the most common being amino acid/peptides, siRNA-based medicines and polyphenols.
CONCLUSIONS
This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment - a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; Biological Products; Dietary Supplements; Vitamin D; Metformin
PubMed: 36329468
DOI: 10.1186/s12916-022-02582-z -
The Medical Letter on Drugs and... Jul 2022
Topics: Anticoagulants; Dabigatran; Humans; Pyridones; Rivaroxaban; Venous Thromboembolism
PubMed: 35867416
DOI: No ID Found -
Case Reports in Cardiology 2023A 45-year-old woman was admitted with severe pain in the right leg and dyspnea. Her medical history included previous endocarditis, biological aortic valve replacement,...
A 45-year-old woman was admitted with severe pain in the right leg and dyspnea. Her medical history included previous endocarditis, biological aortic valve replacement, and intravenous drug abuse. She was febrile but did not have any focal signs of infection. Blood tests showed raised infectious markers and troponin levels. Electrocardiogram showed sinus rhythm without signs of ischemia. Ultrasound revealed thrombosis of the right popliteal artery. The leg was not critically ischemic, and therefore, treatment with dalteparin was chosen. Transesophageal echocardiography showed an excrescence on the biological aortic valve. Empiric treatment for endocarditis was started with intravenous vancomycin, gentamicin, and oral rifampicin. Blood cultures subsequently grew . On day 2, treatment was changed to intravenous cloxacillin. Due to the comorbidity, the patient was not a candidate for the surgical treatment. On day 10, the patient developed moderate expressive aphasia and weakness in the right upper limb. Magnetic resonance imaging showed micro-embolic lesions scattered across both hemispheres of the brain. Treatment was changed from cloxacillin to cefuroxime. On day 42, infectious markers were normal, and echocardiography showed regression of the excrescence. Antibiotic treatment was stopped. Follow-up on day 52 did not show any signs of active infection. However, on day 143, the patient was readmitted with cardiogenic shock due to aortic root fistulation to the left atrium. She quickly deteriorated and died.
PubMed: 37013024
DOI: 10.1155/2023/4624492 -
Pharmacoepidemiology and Drug Safety May 2024Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were... (Comparative Study)
Comparative Study
Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.
PURPOSE
Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer.
METHODS
A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results.
RESULTS
The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups.
CONCLUSIONS
The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.
Topics: Humans; Enoxaparin; Pulmonary Embolism; Venous Thrombosis; Risk Assessment; Neoplasms; Dalteparin; Tinzaparin; Heparin, Low-Molecular-Weight; Anticoagulants; Secondary Prevention; Hemorrhage; Adult
PubMed: 38680090
DOI: 10.1002/pds.5795