Low-Molecular-Weight Heparin versus a Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer

Lee, Agnes Y.Y.; Levine, Mark; Baker, Ross; Bowden, Chris; Kakkar, Ajay K.; Prins, Martin H.; Rickles, Frederick R.; Julian, Jim A.; Haley, Susan L.; Kovacs, Michael J.; Gent, Michael

doi:10.1056/nejmoa025313

Cited by 2,305 publications

(1,556 citation statements)

References 22 publications

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“…Although robust randomized data in patients with malignancy and venous thromboembolism exist,34, 35 generalizability of these results to patients with AF has its limitations given different pathophysiological and risk profiles. The European Society of Cardiology recommends consideration of a DOAC as first‐line therapy in patients with AF for stroke prevention 13.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF‐TIMI 48 Trial

Fanola

Ruff

Murphy

et al. 2018

JAHA

135

113

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BackgroundAnticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse.Methods and ResultsThe ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230–771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78–3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07–2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83–1.42). Relative outcomes with higher‐dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism (HR, 0.60 [95% CI, 0.31–1.15] for malignancy versus HR, 0.89 [95% CI, 0.76–1.05] for no malignancy; interaction P=0.25) and major bleeding (HR, 0.98 [95% CI, 0.69–1.40] for malignancy versus HR, 0.79 [95% CI, 0.69–1.05] for no malignancy; interaction P=0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher‐dose edoxaban versus warfarin in patients with malignancy (HR, 0.54; 95% CI, 0.31–0.93) compared with no malignancy (HR, 1.02; 95% CI, 0.88–1.18; interaction P=0.026).ConclusionsIn patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF‐TIMI 48 Trial

Fanola

Ruff

Murphy

et al. 2018

JAHA

135

113

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“…Thus, the increased risks of major bleeding during anticoagulation in fragile patients could be explained, at least in part, by these other drugs that might have potentiated the effect of the anticoagulant therapy. The similar risk for bleeding than for VTE recurrences in VTE patients weighing ≤50 kg has not been consistently reported 26, 27, 28. These findings suggest the potential benefit of tailored therapy for VTE according to clinical characteristics of the patients and warrant external validation.…”

Section: Discussionmentioning

confidence: 85%

Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Moustafa

Giorgi‐Pierfranceschi²,

Micco

et al. 2017

Research and Practice in Thrombosis and Haemostasis

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Essentials Recent randomized trials suggested fewer bleeding events in fragile patients with VTE receiving DOACs.The frequency, clinical characteristics and outcome of these patients have not been reported in real life.Fragile patients with VTE had a higher risk for major bleeding or death and a lower risk for recurrences than non‐fragile. BackgroundSubgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet.ObjectivesTo compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non‐fragile patients with VTE.MethodsRetrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg.ResultsFrom January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37‐0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10‐1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16‐2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05‐12.4), all‐cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75‐2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10‐2.85) than the non‐fragile.ConclusionsIn real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non‐fragile.

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“…In these studies, LMWH was compared to vitamin K antagonists (VKA) for the treatment of acute VTE in cancer patients. The pivotal CLOT study showed a significant reduction in VTE recurrence,4 while three other smaller studies showed no difference in efficacy or safety outcomes,30, 31, 32 and the most recent CATCH study33 showed a nonsignificant reduction in VTE recurrence, but a significantly decreased risk of clinically relevant non‐major bleeding (CRNMB) in the LMWH arm. We performed a meta‐analysis of the summary data from these studies using Review Manager (RevMan) [Computer program].…”

Section: Treatment Of Cancer‐associated Thrombosismentioning

confidence: 99%

“…Therefore, the optimal prevention and treatment of VTE are crucial components of patient care in this population. Low‐molecular‐weight heparin (LMWH), when compared with warfarin, has been shown to reduce the risk of recurrent VTE in patients with cancer‐associated thrombosis (CAT),4 and is therefore the standard treatment for acute CAT for the past 15 years. However, the high cost and significant lifestyle burden associated with LMWH have led many clinicians and investigators to wonder whether the direct oral anticoagulants (DOACs) might be a better choice for primary and/or secondary VTE prevention in patients with cancer.…”

Section: Introductionmentioning

confidence: 99%

Managing thrombosis in cancer patients

Wang

García

2018

Research and Practice in Thrombosis and Haemostasis

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Venous thromboembolism is a major complication in cancer patients. The basis for the strong association between cancer and thrombosis remains incompletely understood, and the optimal approaches to both the treatment and the prevention of cancer‐associated thrombosis are evolving. Here we review several important topics related to cancer‐associated thromboembolism, including the pathogenesis, prevention, and management of this disease. Wherever possible, we include evidence from clinical trials, including the results of recently published trials that compared direct oral anticoagulants to low‐molecular‐weight heparin for the treatment of cancer‐associated thrombosis.

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Low-Molecular-Weight Heparin versus a Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer

Abstract: In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.

Cited by 2,305 publications

References 22 publications

Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF‐TIMI 48 Trial

Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF‐TIMI 48 Trial

Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Managing thrombosis in cancer patients

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