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Treatment of venous thromboembolism in patients with cancer


Anticoagulation - For patients with active cancer, low-molecular-weight Heparin monotherapy without the transition to oral anticoagulation is preferred over Warfarin ( Coumadin ) by evidence-based guideline recommendations.
In a randomized, controlled trial of 676 patients with cancer, monotherapy with the subcutaneously administered low-molecular-weight Heparin Dalteparin ( Fragmin ) ( 200 IU/kg once daily for 1 month, followed by a daily dose of approximately 150 IU/kg for 5 months ) was compared with oral anticoagulation with a vitamin K antagonist ( target international normalized ratio, INR=2.5 ) for the prevention of recurrent thrombosis in patients who have cancer with acute, symptomatic proximal deep vein thrombosis, pulmonary embolism, or both.
During the 6-month study period, 8% of patients in the Dalteparin group had recurrent venous thromboembolism ( VTE ) in comparison with 15.8% of patients in the oral anticoagulant group ( hazard ratio, HR=0.48; P=0.002 ).
No significant difference in bleeding was noted between the Dalteparin group and the oral anticoagulant group.
A systematic review of randomized, controlled trials comparing long-term treatment with low-molecular-weight heparins versus oral anticoagulants ( vitamin K antagonist or Ximelagatran ) in patients with cancer and symptomatic objectively confirmed venous thromboembolism demonstrated a reduction in VTE ( HR=0.47 ).
No significant difference in the rate of major bleeding was observed between low-molecular-weight heparins and oral anticoagulants ( relative risk, RR=1.05 ).

The role of the novel oral anticoagulants in patients who have cancer with venous thromboembolism has yet to be defined. Randomized, controlled trials evaluating novel oral anticoagulants for treatment of venous thromboembolism have enrolled a small proportion of patients with cancer ( 2–9% ).
The FDA ( Food and Drug Administration ) has approved Rivaroxaban ( Xarelto ) for treatment of venous thromboembolism, but current labeling does not provide specific guidance for those patients with cancer.

Optimal duration of therapy - Because patients who have cancer with venous thromboembolism have an increased risk of recurrent VTE, the 2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy for VTE Disease has recommend extended-duration anticoagulant therapy over time-limited anticoagulation in patients with active cancer, especially if the risk of bleeding is not elevated.

Because patients with cancer who are receiving anticoagulation for VTE treatment have at least a 2-fold increased risk of major bleeding in comparison with patients without cancer who are receiving anticoagulant therapy for venous thromboembolism, patients with cancer who are receiving extended-duration anticoagulation for secondary prevention should be monitored closely for bleeding.

Primary prevention - Because of the increased risk of venous thromboembolism in patients with cancer, especially those undergoing oncological surgery or receiving chemotherapy, thromboprophylaxis for primary prevention of venous thromboembolism has been an important research and clinical practice focus.
In the Enoxaparin and Cancer ( ENOXACAN ) II study, extended-duration ( 4 weeks ) thromboprophylaxis with Enoxaparin ( Clexane ) reduced the risk of venous thromboembolism in patients undergoing laparotomy for abdominal or pelvic malignancy.

The 2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Prevention of VTE in Nonorthopedic Surgical Patients recommends extended duration thromboprophylaxis for patients undergoing surgery for treatment of cancer.

In a registry of 1000 adult hospitalized patients with active cancer, few ( 13.9% ) have received extended-duration pharmacological prophylaxis after hospital discharge.
Venous thromboembolism occurred in 5.4% of hospitalized patients with active cancer over a 90-day follow-up period.
The majority of hospitalized patients with cancer ( 63% ) who developed venous thromboembolism did so after hospital discharge.

A systematic review has evaluated randomized, controlled trials of unfractionated Heparin, low-molecular-weight Heparin, vitamin K antagonists, direct thrombin inhibitors, direct factor Xa inhibitors, or mechanical intervention for primary prevention in medical oncology patients.
Only low-molecular-weight heparins significantly reduced the incidence of symptomatic venous thromboembolism ( risk ratio, RR=0.62 ) in comparison with placebo ( number needed to treat to prevent 1 symptomatic VTE, NNT=60 ).
Low-molecular-weight heparins were not associated with a significantly increased risk of bleeding.
Despite these data, evidence-based clinical practice guidelines do not endorse prophylactic anticoagulation for primary prevention of venous thromboembolism in medical oncology patients. ( Xagena )

Source: American Heart Association, 2013

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