Aspirin, Warfarin, or Enoxaparin Thromboprophylaxis in Patients With Multiple Myeloma Treated With Thalidomide: A Phase III, Open-Label, Randomized Trial.

PurposeIn patients with myeloma, thalidomide significantly improves outcomes but increases the risk ofthromboembolic events. In this randomized, open-label, multicenter trial, we compared aspirin(ASA) or fixed low-dose warfarin (WAR) versus low molecular weight heparin (LMWH) forpreventing thromboembolism in patients with myeloma treated with thalidomide-based regimens.Patients and MethodsA total of 667 patients with previously untreated myeloma who received thalidomide-containingregimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulanttherapy 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.ResultsOf 659 analyzed patients, 43 (6.5%) had serious thromboembolic events, acute cardiovascularevents, or sudden death during the first 6 months (6.4% in the ASA group, 8.2% in the WARgroup, and 5.0% in the LMWH group). Compared with LMWH, the absolute differences were1.3% (95% CI, 3.0% to 5.7%; P .544) in the ASA group and 3.2% (95% CI, 1.5% to7.8%; P .183) in the WAR group. The risk of thromboembolism was 1.38 times higher inpatients treated with thalidomide without bortezomib. Three major (0.5%) and 10 minor (1.5%)bleeding episodes were recorded.ConclusionIn patients with myeloma treated with thalidomide-based regimens, ASA and WAR showed similarefficacy in reducing serious thromboembolic events, acute cardiovascular events, and sudden deathscompared with LMWH, except in elderly patients where WAR showed less efficacy than LMWH.