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1.
Rev Med Suisse ; 15(674): 2232-2235, 2019 Dec 04.
Artigo em Francês | MEDLINE | ID: mdl-31804034

RESUMO

The use of direct oral anticoagulants (DOACs) has been largely -implemented in the management of venous thromboembolic disease in non-cancer patients. In cancer-associated thrombosis, low molecular weight heparins (LMWHs) and especially dalteparin have long been the reference standard therapy. Following the publication of two randomised trials comparing edoxaban and rivaroxaban to -dalteparin, DOACs now represent an alternative with an interesting efficacy and safety profile. Moreover, they offer the comfort of an oral administration and a lower cost. In patients with gastrointestinal or genitourinary cancers however, a higher bleeding risk has been shown with DOACs. LMWHs thus remain the treatment of choice in this group of patients.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/complicações , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Dalteparina/administração & dosagem , Dalteparina/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Rivaroxabana/administração & dosagem , Rivaroxabana/uso terapêutico , Tiazóis/administração & dosagem , Tiazóis/uso terapêutico
3.
J Thromb Thrombolysis ; 48(3): 382-386, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228036

RESUMO

Malignancy is a well-established risk factor for venous thromboembolism and while low-molecular-weight heparin therapy has been standard of care for cancer-associated thrombosis for many years, many patients find injection therapy burdensome. The direct oral anticoagulant edoxaban has been shown to be noninferior to dalteparin for the treatment of cancer-associated thrombosis. In a Markov simulation model, edoxaban with 6-month time horizon and a United States societal perspective with 2017 US dollars, edoxaban was the preferred strategy in the general cancer population (6-month cost $6061 with 0.34 quality adjusted life years) and in a subgroup of patients with gastrointestinal malignancy (6-month cost $7227 with 0.34 quality adjusted life years). The incremental cost effectiveness ratio of dalteparin compared to edoxaban was $1,873,535 in the general oncology population and $694,058 in the gastrointestinal malignancy population.


Assuntos
Análise Custo-Benefício , Dalteparina/uso terapêutico , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Trombose/tratamento farmacológico , Trombose/economia , Anticoagulantes/economia , Anticoagulantes/uso terapêutico , Dalteparina/economia , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/economia , Humanos , Cadeias de Markov , Modelos Teóricos , Neoplasias/complicações , Piridinas/economia , Anos de Vida Ajustados por Qualidade de Vida , Tiazóis/economia , Trombose/etiologia , Estados Unidos
4.
Thromb Res ; 180: 37-42, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31200341

RESUMO

INTRODUCTION: While trials have demonstrated non-inferiority of direct oral anticoagulant drugs (DOAC) to low-molecular-weight heparins (LMWH) for the treatment of cancer associated thrombosis (CAT), it is unclear if the newer intervention is cost-effective. METHODS: We performed a cost-utility analysis using a Markov state-transition model over a time horizon of 60 months in a hypothetical cohort of 65-year-old patients with active malignancy and first acute symptomatic CAT who were eligible to receive either rivaroxaban/edoxaban or dalteparin. We obtained transition probability, relative risk, cost, and utility inputs from the literature. We estimated the differential impact on costs and quality-adjusted life years (QALYs) per patient and performed one-way and probabilistic sensitivity analyses to test the robustness of results. RESULTS: Using the base-case analysis over 60 months, DOAC versus dalteparin was associated with an incremental cost reduction of $24,129 with an incremental QALY reduction of 0.04. In the one-way sensitivity analysis, the cost of dalteparin contributed the most to the incremental cost difference; relative risk of death related to underlying cancer contributed the most of the incremental QALY difference. The probabilistic sensitivity analysis confirmed the base-case analysis, with a large reduction in cost but small reduction in QALYs. CONCLUSION: Rivaroxaban or edoxaban as compared to dalteparin is cost saving from a payer's perspective for the treatment of CAT. Professional organizations and healthcare systems may want to consider this analysis in future practice recommendations.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Piridinas/uso terapêutico , Rivaroxabana/uso terapêutico , Tiazóis/uso terapêutico , Trombose/tratamento farmacológico , Anticoagulantes/economia , Análise Custo-Benefício , Dalteparina/economia , Inibidores do Fator Xa/economia , Humanos , Neoplasias/complicações , Piridinas/economia , Anos de Vida Ajustados por Qualidade de Vida , Rivaroxabana/economia , Tiazóis/economia , Trombose/complicações , Trombose/economia
5.
J Cancer Res Ther ; 14(Supplement): S985-S992, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30539834

RESUMO

Purpose: To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α (HIF-1α) in A549 human lung cancer (LC) cell line and a human A549-grafted nude mouse model. Materials and Methods: A549 human lung adenocarcinoma cell line was divided into control group, treated using normal saline (NS); and dalteparin sodium groups, receiving 5, 15, 50, and 150 IU/ml of dalteparin sodium, respectively. Human A549-grafted nude mouse was induced through subcutaneous (SC) injection of A549 (5 × 106/0.2 ml) into the right armpit, and randomly assigned into control group (n = 6) receiving intraperitoneal (i.p.) injection of NS, cisplatin (DDP) group (n = 6, 3 mg/kg DDP alone, i.p., for 3 days), low molecular weight heparin (LMWH) group (n = 6) receiving SC injection of 1500 IU/kg dalteparin sodium for 35 days, and DDP plus LMWH group (n = 6, 3 mg/kg DDP, i.p., for 3 days, followed by SC injection of 1500 IU/kg dalteparin sodium for 35 days). Results: Significant difference was noted in the messenger RNA expression of VEGF, VEGFR, and HIF-1α after treating with heparin with a concentration of 15, 50, or 150 IU/ml in the A549 cell line at 24 and 48 h, respectively. In the human A549-grafted nude mouse model, a significant reduction was noted in the expression of VEGF, VEGFR, and HIF-1α in the tumor mass harvested from the mice receiving administration of dalteparin sodium plus DDP. Conclusion: Dalteparin sodium had the inhibitory effects on the growth of human LC A549 cells in vitro and A549 LC xenograft model, which could be enhanced when administrated together with DDP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proliferação de Células/efeitos dos fármacos , Dalteparina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Células A549 , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Dalteparina/uso terapêutico , Sinergismo Farmacológico , Feminino , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/patologia , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Thromb Haemost ; 118(12): 2152-2161, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30453352

RESUMO

Most international guidelines recommend pharmacological thromboprophylaxis after total hip and knee arthroplasty (THA/TKA) for 10 to 35 days. However, a recent cohort study on fast-track THA and TKA questioned the need for prolonged thromboprophylaxis when length of stay (LOS) is ≤ 5 days. We aimed at re-investigating the incidence of venous thromboembolism (VTE) in fast-track THA and TKA with in-hospital only thromboprophylaxis when LOS was ≤ 5 days. Prospective cohort study from 1 December 2011 to 30 October 2015 on elective unilateral THA/TKA with in-hospital only thromboprophylaxis if LOS was ≤ 5 days. Prospective information on co-morbidity and complete 90-day follow-up through the Danish National Patient Registry and medical records. Patients with pre-operative use of anticoagulants were excluded. In per protocol analysis, 17,582 (95.5%) had LOS of ≤ 5 days (median, 2 [interquartile range, 2-3]) and in-hospital thromboprophylaxis only. Incidence of symptomatic VTE was 0.40%, consisting of 28 (0.16%) pulmonary embolisms (PEs), 38 (0.22%) deep vein thrombosis (DVT) and 4 (0.02%) combined DVT and PE. Two PEs (0.01%) were fatal. VTE-associated risk factors with in-hospital only thromboprophylaxis were age > 85 years, odds ratio (OR) of 3.74 (95% confidence interval: 1.15-12.14, p = 0.028), body mass index (BMI) of 35 to 40, OR of 2.55 (1.02-6.35, p = 0.045) and BMI > 40, OR of 3.28 (1.02-10.56, p = 0.046). In conclusion, 90-day incidence of VTE after fast-track THA and TKA with in-hospital thromboprophylaxis only was 0.40%. Prolonged thromboprophylaxis may be reserved for LOS > 5 days or specific high-risk patients, but requires further studies regarding optimal type and duration of thromboprophylaxis.


Assuntos
Anticoagulantes/uso terapêutico , Artroplastia de Quadril , Artroplastia do Joelho , Complicações Pós-Operatórias/epidemiologia , Tromboembolia Venosa/epidemiologia , Idoso , Dalteparina/uso terapêutico , Dinamarca/epidemiologia , Enoxaparina/uso terapêutico , Seguimentos , Hospitais , Humanos , Incidência , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Risco , Rivaroxabana/uso terapêutico , Análise de Sobrevida , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/prevenção & controle
7.
Thromb Haemost ; 118(9): 1668-1678, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30103252

RESUMO

International and national guidelines recommend low-molecular-weight heparin for the treatment of venous thromboembolism (VTE) in patients with cancer. The aim of the Caravaggio study is to assess whether oral apixaban is non-inferior to subcutaneous dalteparin for the treatment of acute proximal deep vein thrombosis and/or pulmonary embolism in patients with cancer. The study is an investigator-initiated, multi-national, prospective, randomized, open-label with blind end-point evaluation (PROBE), non-inferiority clinical trial (NCT03045406). Consecutive patients are randomized to receive oral apixaban or subcutaneous dalteparin for 6 months. Apixaban is given at a dose of 10 mg twice daily for the first 7 days and then 5 mg twice daily; dalteparin is given at a dose of 200 IU/kg for the first month and then 150 IU/kg once daily. The primary outcome of the study is objectively confirmed recurrent VTE as assessed by a central independent adjudication committee unaware of study treatment allocation. The primary safety outcome is major bleeding defined according to the guidelines of the International Society of Thrombosis and Haemostasis. Assuming a 6-month incidence of the primary outcome of 7% with dalteparin and an upper limit of the two-sided 95% confidence interval of the hazard ratio below the pre-specified margin of 2.00, 1,168 patients will be randomized considering an up to 20% loss in total patient-years (ß = 80%; α one-sided = 0.025). The Caravaggio study has the potential, along with other recently performed or on-going studies, to make less cumbersome the management of VTE in patients with cancer by replacing parenteral with oral anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Neoplasias/tratamento farmacológico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Doença Aguda , Administração Oral , Adulto , Europa (Continente) , Seguimentos , Humanos , Neoplasias/complicações , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos , Tromboembolia Venosa/complicações
8.
Medicine (Baltimore) ; 97(32): e11810, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30095650

RESUMO

RATIONALE: Treprostinil, a potent vasodilator, is the treatment of choice for severe pulmonary arterial hypertension (PAH) during pregnancy. Its inhibition of platelet aggregation increases the risk of hemorrhage. In addition, anticoagulation therapy is widely used in pregnancy with PAH due to the hypercoagulable state. However, very little is known about the complications of anticoagulants' use in pregnancy with PAH. PATIENT CONCERNS: A 27-year-old pregnant woman was admitted to the hospital at 32weeks with progressive dyspnea. DIAGNOSES: The pregnant was diagnosed with ventricular septal defect 12 years prior to presentation. Combining clinical manifestation with results of right heart catheterization (RHC) and echocardiography, it was consistent with severe World Health Organization (WHO) group I PAH. INTERVENTIONS: Supportive treatment included supplemental oxygen, intravenous treprostinil, sildenafil and prophylactic anticoagulation. OUTCOMES: Gastrointestinal bleeding is occurred in our patient when dalteparin were used in conjunction with treprostinil. Her care was further complicated refractory to usual conservative measures before delivery. LESSONS: This case report illustrates the complexities that arise when prostacyclin therapies are combined with necessary anticoagulation in patients with PAH during pregnancy. More intention should play to the complications of anticoagulant in pregnancy with PAH during treprostinil therapy.


Assuntos
Anticoagulantes/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Dalteparina/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Dalteparina/administração & dosagem , Dalteparina/efeitos adversos , Epoprostenol/análogos & derivados , Epoprostenol/uso terapêutico , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Gravidez , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico
9.
J Thromb Haemost ; 16(9): 1891-1894, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30027649
10.
J Clin Oncol ; 36(20): 2017-2023, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29746227

RESUMO

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Neoplasias/sangue , Tromboembolia Venosa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes , Dalteparina/uso terapêutico , Feminino , Fibrinolíticos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Projetos Piloto , Rivaroxabana/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento
11.
Int J Surg ; 54(Pt A): 265-275, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29733996

RESUMO

BACKGROUND: To systematically evaluate the prophylaxis efficacy of low-molecular-weight heparin (LMWH) in the prevention of deep venous thrombosis (DVT) after total knee arthroplasty (TKA). METHOD: PubMed, Cochrane, Embase, Wanfang, CNKI, and VIP databases were searched by index words to identify the eligible RCTs; relevant literature sources were also searched. The latest research was conducted in March 2017. Relative risks (RR), mean difference (MD), and their corresponding 95% confidence intervals (95% CIs) were used to analyze the main outcomes. RESULT: A total of 22 articles were included in the meta-analysis with a total number of 11,320 patients (5543 in the LMWH group and 5777 in the control group). The results indicated that in the LMWH group, the incidence of DVT (OR: 0.57, 95% CI: 0.41-0.77) and wound complications (SMD: 0.96, 95% CI: 0.75-1.22) was significantly lower than that in the control group. Furthermore, LMWH also increased the occurrence of bleeding event (OR: 1.57, 95% CI: 1.31-1.88) and the total blood transfused (SMD: 0.12, 95% CI: 0.04-0.19). However, no statistical difference was found in blood loss (SMD: -0.26, 95% CI: -0.65-0.14) between the two group. In the subgroup analysis, the incidence of DVT was significantly decreased in the ardeparin sodium group (OR: 0.70, 95%CI: 0.53-0.94) and the dalteparin group (OR:0.40, 95%CI:0.32-0.50). CONCLUSION: Our meta-analysis demonstrated that LMWH is obviously efficacious in the prophylaxis of DVT after TKA. However, it has some negative effects, such as the increase in the number of bleeding events and the total blood transfused.


Assuntos
Anticoagulantes/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Trombose Venosa/prevenção & controle , Idoso , Transfusão de Sangue/estatística & dados numéricos , Dalteparina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Hemorragia Pós-Operatória/etiologia , Trombose Venosa/etiologia
12.
Expert Rev Hematol ; 11(6): 487-494, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29791257

RESUMO

INTRODUCTION: After the CLOT study, LMWHs (low-molecular weight heparins) have gradually replaced warfarin as the treatment of choice for VTE (venous thromboembolism) in cancer patients. Randomized controlled studies comparing DOACs (direct oral anticoagulants) to LMWHs in cancer patients are still limited. However, new emerging data are supporting the use of DOACs in cancer-associated thrombosis. Areas covered: This review will discuss the recent studies that addressed the utilization of such agents in the treatment of VTE in cancer patients. It will also address challenges that can be encountered while using these agents particularly in cancer patients. Expert commentary: Up until the Hokusai VTE Cancer study, data on the use of DOACs in cancer patients have been limited but supportive of their use in such patients. The Hokusai VTE Cancer study shows that edoxaban is non-inferior to dalteparin in prevention of recurrent VTE but at expense of higher major bleeding namely in patients with gastrointestinal cancer. Although further studies involving other DOACs may reinforce the efficacy of DOACs in this population of patients, studies looking at subpopulation of cancer patients may be of more clinical value to clinicians who are trying to balance between treatment of thrombosis and risks of bleeding.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Neoplasias Gastrointestinais/terapia , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Doença Aguda , Administração Oral , Dalteparina/efeitos adversos , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/patologia , Humanos , Piridinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiazóis/efeitos adversos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/patologia
13.
Pharmacol Res ; 131: 211-217, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29452290

RESUMO

Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size descriptors (BSD) on peak anti-Xa levels in BS obese patients receiving LMWH fixed doses to identify which one had the greatest impact. One hundred and thirteen BS obese patients [median body mass index (BMI), 43.3 kg/m2 (IQR, 40.6-48.7 kg/m2)] receiving subcutaneous dalteparin 5000 IU twice daily were included in this prospective monocenter study. Peak steady-state anti-Xa levels were measured peri-operatively following thromboprophylaxis initiation. Only 48% of patients achieved target anti-Xa levels (0.2-0.5 IU/ml). In univariate analysis, age, gender, total body-weight (TBW), lean body-weight (LBW), ideal body-weight (IBW), BMI and estimated glomerural filtration rate (eGFR) were associated with anti-Xa levels. The strongest negative association was observed with LBW (r = -0.56, p < .0001). Receiver operating characteristic curves indicated that among BSD, LBW (cut-off >55.8 kg) had the highest sensitivity (73%) and specificity (69%) to predict sub-prophylactic anti-Xa levels. In multivariate analysis, LBW and eGFR remained associated with anti-Xa levels (ß = -0.47 ±â€¯0.08, p < .0001 and ß = -0.19 ±â€¯0.08; p = .02, respectively). In BS morbidly obese patients receiving LMWH for thromboprophylaxis after BS, LBW and eGFR are the main determinants of anti-Xa level, and could be proposed in LMWH-based thromboprophylaxis dosing algorithms. The efficacy of a LBW-scale based dosing algorithm for optimal VTE prevention deserves further prospective randomized trials.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Adulto , Cirurgia Bariátrica , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Peso Corporal Ideal , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Perda de Peso
14.
Cochrane Database Syst Rev ; 1: CD006649, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29363105

RESUMO

BACKGROUND: Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. OBJECTIVES: To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer. SEARCH METHODS: A comprehensive search included a major electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (2018, Issue 1), MEDLINE (via Ovid) and Embase (via Ovid); handsearching of conference proceedings; checking of references of included studies; use of the 'related citation' feature in PubMed; and a search for ongoing studies. This update of the systematic review was based on the findings of a literature search conducted on 14 January 2018. SELECTION CRITERIA: Randomized controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE. DATA COLLECTION AND ANALYSIS: Using a standardized form, we extracted data in duplicate on study design, participants, interventions outcomes of interest, and risk of bias. Outcomes of interested included all-cause mortality, symptomatic VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: Of 15440 identified citations, 7387 unique citations, 15 RCTs fulfilled the eligibility criteria. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH enrolling 1025 participants, one compared fondaparinux with UFH and LMWH enrolling 477 participants, and one compared dalteparin with tinzaparin enrolling 113 participants. The meta-analysis of mortality at three months included 418 participants from five studies and that of recurrent VTE included 422 participants from 3 studies. The findings showed that LMWH likely decreases mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; moderate certainty evidence), but did not rule out a clinically significant increase or decrease in VTE recurrence (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; moderate certainty evidence).The study comparing fondaparinux with heparin (UFH or LMWH) did not exclude a beneficial or detrimental effect of fondaparinux on mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; moderate certainty evidence), recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; moderate certainty evidence), major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; moderate certainty evidence), or minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence)The study comparing dalteparin with tinzaparin did not exclude a beneficial or detrimental effect of dalteparin on mortality (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), major bleeding (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), or minor bleeding (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence). AUTHORS' CONCLUSIONS: LMWH is possibly superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Dalteparina/uso terapêutico , Fibrinolíticos/uso terapêutico , Fondaparinux , Hemorragia/induzido quimicamente , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Polissacarídeos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Prevenção Secundária , Tinzaparina , Tromboembolia Venosa/mortalidade
16.
N Engl J Med ; 378(7): 615-624, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29231094

RESUMO

BACKGROUND: Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear. METHODS: In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration. RESULTS: Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P=0.006 for noninferiority; P=0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6). CONCLUSIONS: Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials.gov number, NCT02073682 .).


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Neoplasias/complicações , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Adulto , Idoso , Anticoagulantes/efeitos adversos , Dalteparina/efeitos adversos , Seguimentos , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Piridinas/efeitos adversos , Recidiva , Tiazóis/efeitos adversos , Tromboembolia Venosa/etiologia
17.
Am Heart J ; 195: 108-114, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29224638

RESUMO

BACKGROUND: The use of low-molecular weight heparin bridge therapy during warfarin interruption for elective surgery/procedures increases bleeding. Other predictors of bleeding in this setting are not well described. METHODS: BRIDGE was a randomized, double-blind, placebo-controlled trial of bridge therapy with dalteparin 100 IU/kg twice daily in patients with atrial fibrillation requiring warfarin interruption. Bleeding outcomes were documented from the time of warfarin interruption until up to 37 days postprocedure. Multiple logistic regression and time-dependent hazard models were used to identify major bleeding predictors. RESULTS: We analyzed 1,813 patients of whom 895 received bridging and 918 received placebo. Median patient age was 72.6 years, and 73.3% were male. Forty-one major bleeding events occurred at a median time of 7.0 days (interquartile range, 4.0-18.0 days) postprocedure. Bridge therapy was a baseline predictor of major bleeding (odds ratio [OR]=2.4, 95% CI: 1.2-4.8), as were a history of renal disease (OR=2.9, 95% CI: 1.4-6.0), and high-bleeding risk procedures (vs low-bleeding risk procedures) (OR=2.9, 95% CI: 1.4-5.9). Perioperative aspirin use (OR=3.6, 95% CI: 1.1-11.9) and postprocedure international normalized ratio >3.0 (OR=2.1, 95% CI: 1.5-3.1) were time-dependent predictors of major bleeding. Major bleeding was most common in the first 10 days compared with 11-37 days postprocedure (OR=3.5, 95% CI: 1.8-6.9). CONCLUSIONS: In addition to bridge therapy, perioperative aspirin use, postprocedure international normalized ratio >3.0, a history of renal failure, and having a high-bleeding risk procedure increase the risk of major bleeding around the time of an elective surgery/procedure requiring warfarin interruption.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Dalteparina/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Hemorragia Pós-Operatória/etiologia , Acidente Vascular Cerebral/prevenção & controle , Varfarina/farmacologia , Suspensão de Tratamento , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Dalteparina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Incidência , Injeções Subcutâneas , Masculino , North Carolina/epidemiologia , Hemorragia Pós-Operatória/epidemiologia , Acidente Vascular Cerebral/etiologia
18.
Thromb Haemost ; 117(10): 1952-1961, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28837207

RESUMO

Currently, low molecular weight heparin (LMWH) is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, there are limited data supporting its use in cancer patients. The rationale and design of this investigator initiated Phase IV, multicenter, randomized, open label, superiority trial assessing the safety of apixaban versus dalteparin for cancer associated VTE is provided (ADAM-VTE; NCT02585713). The main aim of the ADAM-VTE trial is to test the hypothesis that apixaban is associated with a significantly lower rate of major bleeding compared to dalteparin in the treatment of cancer patients with acute VTE. The primary safety outcome is rate of major bleeding. Secondary efficacy objective is to assess the rates of recurrent VTE or arterial thromboembolism. Cancer patients with acute VTE (n=300) are randomized to receive apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily thereafter) or dalteparin (200 IU/Kg daily for 30 days followed by 150 IU/kg daily thereafter) for 6 months. Stratification factors used for randomization include cancer stage and cancer specific risk of venous thromboembolism using the Khorana score. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium comprised of 90 oncology practices in the United States and Canada. Based on the hypothesis to be tested, we anticipate that these trial results will provide evidence supporting apixaban as an effective treatment of cancer associated VTE at lower rates of major bleeding compared to LMWH.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Neoplasias/complicações , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/efeitos adversos , Canadá , Dalteparina/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Neoplasias/sangue , Neoplasias/diagnóstico , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia
19.
J Obstet Gynaecol Can ; 39(8): 676-681, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28456434

RESUMO

BACKGROUND: Massive perivillous fibrin deposition (MPVFD) and chronic intervillositis (CI) are related rare pathological correlates of severe intrauterine growth restriction (IUGR) and fetal loss with high recurrence rates. No standard management has been established. CASE: A patient underwent termination of pregnancy at 21 weeks for severe early onset IUGR. Placental histology showed mixed CI with MPVFD. Several months later, the patient became pregnant and was managed with prednisone and aspirin (ASA) but miscarried at 16 weeks. Placental pathology showed MPVFD and focal CI. For two subsequent pregnancies, she was treated with intravenous immunoglobulin (IVIG), heparin, and ASA. Both pregnancies resulted in healthy near-term deliveries with normal placentas. CONCLUSION: IVIG, heparin, and ASA can be an option in patients with recurrent pregnancy loss due to MPVFD and CI.


Assuntos
Aborto Habitual/prevenção & controle , Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Fibrina , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Doenças Placentárias/tratamento farmacológico , Placenta/patologia , Aborto Habitual/etiologia , Aborto Espontâneo , Adulto , Aspirina/uso terapêutico , Vilosidades Coriônicas/patologia , Feminino , Retardo do Crescimento Fetal , Humanos , Doenças Placentárias/patologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Gravidez
20.
Support Care Cancer ; 25(7): 2093-2102, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28204995

RESUMO

BACKGROUND: International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives. METHODS: Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained. RESULTS: The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p < 0.001). However, when the incremental costs were combined with the utility gain, dalteparin had a cost of €6600 and €4900 per QALY gained in Austria and France, respectively. The analyses in patients with renal impairment suggested an even better economic profile, with the cost per QALY gained being less than €4000 in both countries. CONCLUSIONS: Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Neoplasias/complicações , Qualidade de Vida/psicologia , Tromboembolia Venosa/economia , Tromboembolia Venosa/prevenção & controle , Vitamina K/antagonistas & inibidores , Áustria , Análise Custo-Benefício , Dalteparina/administração & dosagem , Dalteparina/farmacologia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Recidiva
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