title: Long-term treatment of venous thromboembolism with tinzaparin compared to vitamin K antagonists: a meta-analysis of 5 randomized trials in non-cancer and cancer patients.
abstract: OBJECTIVE
  Due to its specific pharmacokinetic profile, tinzaparin, a low-molecular-weight heparin (LMWH), appears not to be associated with anti-factor Xa accumulation. Our meta-analysis aimed at determining whether long-term curative doses of tinzaparin is a valuable alternative to vitamin K antagonists (VKA) for the treatment of symptomatic venous thromboembolism (VTE), especially in patients with cancer who are at higher risk of recurrence and bleeding.
  
  
  METHODS
  A systematic literature search identified randomized studies on long-term tinzaparin compared to VKA in patients with VTE. Outcome measures were VTE recurrence, major bleeding, deaths and net clinical benefit combining the three endpoints during the treatment period and at one year. Pooled relative risk was estimated using the logarithm of the relative risk (RR) method based on a fixed-effect model in the overall population and cancer population.
  
  
  RESULTS
  Five randomized controlled studies were eligible. No difference between groups in VTE recurrence was found in the overall population (RR=0.85 [0.55; 1.31]). In cancer patients, a non-significant 38% VTE risk reduction in favor of tinzaparin was observed on treatment (RR=0.62 [0.30; 1.31]). The difference was significant at the end of follow-up at one year (RR=0.40 [0.19; 0.82], p<0.01). The incidence of major bleeding in the tinzaparin group was not significantly different from the VKA group in the overall population and cancer patients.
  
  
  CONCLUSIONS
  Tinzaparin appears as a valuable option for long-term treatment of patients in whom VKA are contraindicated or difficult to monitor. Tinzaparin may have a more favorable benefit-risk ratio than VKA in patients with cancer and VTE.
authors.affiliation: Dept. of Clinical Pharmacology Hospital of Saint-Etienne, France. Silvy.laporte@chu-st-etienne.fr
authors.forename: Silvy
authors.initials: S
authors.lastname: Laporte
authors.forename: Laurent
authors.initials: L
authors.lastname: Bertoletti
authors.forename: Antonio
authors.initials: A
authors.lastname: Romera
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez de Llano
authors.forename: Guy
authors.initials: G
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D000078222:Tinzaparin; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications* / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K; D000078222:Tinzaparin