article232

CLOT

"Dalteparin versus Oral Anticoagulant Therapy for the Prevention of Recurrence in Patients with Cancer and Venous Thromboembolism". The New England Journal of Medicine. Year published and issue details not provided in the text.

Clinical Question

Does low-molecular-weight heparin (dalteparin) reduce the risk of recurrent venous thromboembolism in patients with cancer more effectively than oral anticoagulant therapy without increasing the risk of bleeding?

Bottom Line

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

Major Points

Guidelines

Guideline recommendations for anticoagulation in patients with cancer and venous thromboembolism were not provided in the article.

Design

- Multicenter, randomized, open-label clinical trial
- N=676 patients with cancer and acute venous thromboembolism
- Dalteparin versus oral anticoagulant therapy
- Mean follow-up: 6 months

Population

- Adult patients with active cancer and newly diagnosed, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both.
- Exclusion criteria included pregnancy, baseline platelet count less than 75,000/mm³, and others related to anticoagulant therapy contraindications.

Interventions

- Dalteparin: 200 IU/kg subcutaneously once daily for the first month, followed by approximately 150 IU/kg for five months.
- Oral anticoagulant therapy: Initial therapy with dalteparin for five to seven days until INR within therapeutic range, followed by warfarin or acenocoumarol for six months (target INR, 2.5).

Outcomes

- Primary Outcome: First episode of objectively documented, symptomatic, recurrent venous thromboembolism during six-month study period.
- 27 occurrences in the dalteparin group versus 53 in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002).
- Secondary Outcomes: Major bleeding and any bleeding events.
- Major bleeding: 6% in the dalteparin group, 4% in the oral-anticoagulant group (P=0.27).
- Any bleeding: 14% in the dalteparin group, 19% in the oral-anticoagulant group (P=0.09).
- Mortality rate at six months: 39% in the dalteparin group, 41% in the oral-anticoagulant group (P=0.53).

Criticisms

The open-label design may have introduced reporting and diagnostic bias. Frequent contact and the use of objective tests for assessing suspected events, along with review by a blinded central committee, were methods utilized to mitigate this bias.

Funding

Pharmacia Corporation.