title: Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Torino, Azienda Ospedaliero-Universitaria San Giovanni Battista, Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Elena
authors.initials: E
authors.lastname: Zamagni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romano
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Fabiana
authors.initials: F
authors.lastname: Gentilini
authors.forename: Claudia
authors.initials: C
authors.lastname: Crippa
authors.forename: Monica
authors.initials: M
authors.lastname: Galli
authors.forename: Chiara
authors.initials: C
authors.lastname: Nozzoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Ria
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.forename: Vittorio
authors.initials: V
authors.lastname: Montefusco
authors.forename: Luca
authors.initials: L
authors.lastname: Baldini
authors.forename: Francesca
authors.initials: F
authors.lastname: Elice
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Callea
authors.forename: Stefano
authors.initials: S
authors.lastname: Pulini
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Carella
authors.forename: Renato
authors.initials: R
authors.lastname: Zambello
authors.forename: Giulia
authors.initials: G
authors.lastname: Benevolo
authors.forename: Valeria
authors.initials: V
authors.lastname: Magarotto
authors.forename: Paola
authors.initials: P
authors.lastname: Tacchetti
authors.forename: Norbert
authors.initials: N
authors.lastname: Pescosta
authors.forename: Claudia
authors.initials: C
authors.lastname: Cellini
authors.forename: Claudia
authors.initials: C
authors.lastname: Polloni
authors.forename: Andrea
authors.initials: A
authors.lastname: Evangelista
authors.forename: Tommaso
authors.initials: T
authors.lastname: Caravita
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tosi
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage; D013923:Thromboembolism / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D013792:Thalidomide; D014859:Warfarin; D001241:Aspirin