title: Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long-term recurrence.
abstract: OBJECTIVE
  Several factors are associated with an increased risk of recurrent venous thromboembolism (VTE). The aim of the study was to investigate whether the quality of oral anticoagulation therapy (OAT) is a long-term risk factor for recurrence of VTE after OAT interruption.
  
  
  RESULTS
  A total of 297 patients (170 males) with a recent acute unprovoked VTE episode were prospectively monitored during OAT in our anticoagulation clinic and followed up for 21 months after OAT interruption. Recurrent events were recorded in 42 subjects for 493 years of follow-up [14.1% of patients; 8.5% patient-years (pt-y)] after OAT withdrawal. The rate of recurrence was not correlated to OAT duration. Subjects experiencing recurrence after OAT interruption had spent significantly more time at markedly subtherapeutic international normalized ratio (INR) levels (<1.5) and less time within the therapeutic range (2.0-3.0 INR) during OAT. Relative risk (RR) of recurrence was significantly higher [2.77 (95% confidence interval (CI) 1.49-5.18; P = 0.001) and 2.70 (95% CI 1.39-5.25; P = 0.003) at univariate and multivariate analysis, respectively] in those who spent more time (upper quintile) at INR values <1.5, being especially evident in the first 90 days of OAT. RR was significantly higher at univariate [2.05 (95% CI 1.07-3.96; P = 0.031)] but not at multivariate [1.98 (95% CI 0.98-4.0; P = 0.056)] analysis when the entire OAT period was considered. Subjects in the upper quintile of time spent at INR values <1.5 had significantly higher D-dimer values when OAT was stopped and after 3 months.
  
  
  CONCLUSIONS
  The amount of time that subjects with an acute unprovoked VTE event spend at near-normal INR values (<1.5) during the first 3 months of treatment is associated with higher D-dimer values measured during OAT and after its interruption and is a significant risk factor for late VTE recurrence.
authors.affiliation: Department of Angiology & Blood Coagulation Marino Golinelli, University Hospital S. Orsola-Malpighi, Bologna, Italy. palareti@tin.it
authors.forename: G
authors.initials: G
authors.lastname: Palareti
authors.forename: C
authors.initials: C
authors.lastname: Legnani
authors.forename: B
authors.initials: B
authors.lastname: Cosmi
authors.forename: G
authors.initials: G
authors.lastname: Guazzaloca
authors.forename: M
authors.initials: M
authors.lastname: Cini
authors.forename: S
authors.initials: S
authors.lastname: Mattarozzi
mesh_terms: D000074:Acenocoumarol / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000096:biosynthesis; D006493:Heparin / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000401:mortality; D012008:Recurrence; D012044:Regression Analysis; D012306:Risk; D012307:Risk Factors; D013923:Thromboembolism / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy*; D014859:Warfarin / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D006495:Heparin, Low-Molecular-Weight; C036309:fibrin fragment D; D014859:Warfarin; D006493:Heparin; D000074:Acenocoumarol