title: Risk of recurrent venous thromboembolism after discontinuation of vitamin K antagonist treatment: a nested case-control study.
abstract: Essentials Vitamin K antagonists (VKA) in venous thromboembolism (VTE) lower the risk of recurrences. 41 841 VKA-treated VTE patients had 1242 recurrent VTEs on therapy or early after cessation. An increased risk of recurrence was found in the first 120 days after VKA cessation. Patient education for the early detection of recurrent VTE after VKA cessation is recommended.
  
  
  
  Background The standard treatment for venous thromboembolism (VTE) and the prevention of recurrent VTE (rVTE) consists of anticoagulant therapy. The optimal duration of anticoagulation depends on the presence of risk factors for rVTE. Objectives To estimate the risk of rVTE in association with time since discontinuation of vitamin K antagonist (VKA) treatment. Methods From the UK Clinical Practice Research Datalink with linked information on hospitalization and cause of death, a cohort of patients with a first VTE receiving initial VKA treatment between 2001 and 2013 was formed. With a nested case-control approach, patients with incident rVTE (cases) were matched to patients with VTE but without rVTE (controls). Adjusted rate ratios (RRs) of rVTE associated with time since VKA discontinuation relative to current VKA use were estimated from conditional logistic regression. Results The VTE cohort comprised 41 841 patients with 1242 rVTEs and 6205 matched controls. The RR of rVTE was increased within 60 days following VKA discontinuation (RR 2.23, 95% confidence interval [CI] 1.71-2.91) and within 61-120 days following VKA discontinuation (RR 1.49, 95% CI 1.08-2.05) relative to current VKA use. The increased RR corresponded to excess incidence rates of 6.72 (95% CI 3.90-10.06) rVTE cases per 100 person-years within 60 days, and of 2.68 (95% CI 0.42-5.58) rVTE cases per 100 person-years within 61-120 days after VKA discontinuation. Conclusions VKA discontinuation results in a transient increased risk of rVTE, which peaks within 60 days and lasts for up to 120 days after VKA discontinuation. Specific patient education for increased vigilance for signs and symptoms of recurrences is recommended in this period.
authors.affiliation: Institute for Epidemiology, Statistics and Informatics, Frankfurt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Martinez
authors.affiliation: Institute for Epidemiology, Statistics and Informatics, Frankfurt, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Katholing
authors.affiliation: Bayer Pharma AG, Global Market Access GHEOR GM, Wuppertal, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Folkerts
authors.affiliation: Department of Haematological Medicine, Guys and St Thomas' Hospitals, King's College Hospital, London, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Cohen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010353:Patient Education as Topic; D012008:Recurrence; D012044:Regression Analysis; D012307:Risk Factors; D006113:United Kingdom; D054556:Venous Thromboembolism / Q000175:diagnosis* / Q000209:etiology*; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D014812:Vitamin K
keywords: anticoagulants; nested case-control studies; recurrence; venous thromboembolism; warfarin