February 1, 2011Journal of Clinical Oncology325 citationsOpen Access
Aspirin, Warfarin, or Enoxaparin Thromboprophylaxis in Patients With Multiple Myeloma Treated With Thalidomide: A Phase III, Open-Label, Randomized Trial
Structured PICO
Does aspirin or low-dose warfarin prevent serious thromboembolic events, acute cardiovascular events, or sudden deaths compared to LMWH in patients with multiple myeloma treated with thalidomide?
P
Population
667 patients with previously untreated multiple myeloma receiving thalidomide-containing regimens, with no clinical indication or contraindication for specific antiplatelet or anticoagulant therapy
I
Intervention
Aspirin (100 mg/d) or fixed low-dose warfarin (1.25 mg/d)
C
Comparator
Low molecular weight heparin (enoxaparin 40 mg/d)
O
Outcome
Composite of serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatmentcomposite
Aspirin and low-dose warfarin demonstrated similar efficacy to LMWH for thromboprophylaxis in multiple myeloma patients treated with thalidomide, except in elderly patients where warfarin was less effective.
Abstract
PURPOSE: In patients with myeloma, thalidomide significantly improves outcomes but increases the risk of thromboembolic events. In this randomized, open-label, multicenter trial, we compared aspirin (ASA) or fixed low-dose warfarin (WAR) versus low molecular weight heparin (LMWH) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens. PATIENTS AND METHODS: A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were randomly assigned to receive ASA (100 mg/d), WAR (1.25 mg/d), or LMWH (enoxaparin 40 mg/d). A composite primary end point included serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment. RESULTS: Of 659 analyzed patients, 43 (6.5%) had serious thromboembolic events, acute cardiovascular events, or sudden death during the first 6 months (6.4% in the ASA group, 8.2% in the WAR group, and 5.0% in the LMWH group). Compared with LMWH, the absolute differences were +1.3% (95% CI, -3.0% to 5.7%; P = .544) in the ASA group and +3.2% (95% CI, -1.5% to 7.8%; P = .183) in the WAR group. The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib. Three major (0.5%) and 10 minor (1.5%) bleeding episodes were recorded. CONCLUSION: In patients with myeloma treated with thalidomide-based regimens, ASA and WAR showed similar efficacy in reducing serious thromboembolic events, acute cardiovascular events, and sudden deaths compared with LMWH, except in elderly patients where WAR showed less efficacy than LMWH.