Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism

Ridker, P.I.M.; Goldhaber, S.Z.; Danielson, Eleanor

doi:10.1016/s1062-1458(03)00259-9

Cited by 100 publications

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“…4 In patients without reversible risk factors, the risk of recurrent venous thromboembolism is as much as 10% in the first year if anticoagulation therapy is stopped. [5][6][7][8][9] Patients in whom thrombosis was triggered by nonsurgical risk factors or who have persistent risk factors are at higher risk for recurrence than are those with postoperative thrombosis. 10 In addition, because of overlapping risk factors, patients with venous thromboembolism are at increased risk for arterial thrombotic events, including myocardial infarction, stroke, and vascular death.…”

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“…10 In addition, because of overlapping risk factors, patients with venous thromboembolism are at increased risk for arterial thrombotic events, including myocardial infarction, stroke, and vascular death. [11][12][13] Although extended anticoagulation therapy is effective for the prevention of recurrent venous thromboembolism, [5][6][7][8][9] concern about bleeding often leads to a reluctance to continue anticoagulant treatment beyond 6 to 12 months. Attempts to reduce the risk of bleeding when treatment is extended include the use of lower-dose anticoagulant therapy and the use of aspirin in place of an anticoagulant agent.…”

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“…Attempts to reduce the risk of bleeding when treatment is extended include the use of lower-dose anticoagulant therapy and the use of aspirin in place of an anticoagulant agent. 6,[12][13][14] At a dose of 20 mg once daily, rivaroxaban is effective for stroke prevention in patients with atrial fibrillation 15 and for the treatment of venous thromboembolism after an initial 21-day course of higher-dose therapy. 7,16,17 At a dose of 10 mg once daily, rivaroxaban provides effective thromboprophylaxis after elective hip or knee arthroplasty.…”

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Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

et al. 2017

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BACKGROUNDAlthough many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full-or lower-intensity anticoagulation therapy or aspirin. METHODSIn this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding. RESULTSA total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups. CONCLUSIONSAmong patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439.) a bs tr ac t

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Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

et al. 2017

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“…In the ELATE trial, reduced-intensity warfarin was possibly less effective in preventing recurrence compared to standard-intensity warfarin (1.9% vs. 0.9% recurrence), while the risk of bleeding approached that of standard therapy (1.1% vs. 0.9%). 12 Extending anticoagulant therapy for VTE from 3 to 12 months only delayed the time at which recurrence occurred following cessation without impacting on the frequency of recurrence. 13 Current American College of Chest Physician (ACCP) guidelines 14 suggest that individuals with previous VTE in association with ATIII deficiency, homozygous thrombophilic defect or heterozygosity for two or more prothrombotic defects merit indefinite anticoagulation.…”

Section: Duration Of Anticoagulant Therapymentioning

confidence: 99%

Management of Hereditary Hypercoagulable Disorders

Bockenstedt¹

2006

Hematology

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The clinical management of individuals with hereditary hypercoaguable disorders has evolved from initial broad recommendations of lifelong anticoagulation after first event of venous thromboembolism to a more intricate individualized risk-benefit analysis as studies have begun to delineate the complexity of interactions of acquired and hereditary factors which determine the predilection to thrombosis. The contribution of thrombophilic disorders to risk of thrombotic complications of pregnancy, organ transplantation, central venous catheter and dialysis access placement have been increasingly recognized. The risk of thrombosis must be weighed against risk of long-term anticoagulation in patients with venous thromboembolism. Thrombophilia screening in select populations may enhance outcome. Initial DecisionsThe clinical management of individuals with hereditary hypercoagulable disorders has evolved from initial broad recommendations of lifelong anticoagulation after first event of venous thromboembolism (VTE) to a more intricate, individualized risk-benefit analysis as the complexity of interactions of acquired and hereditary factors that determine the predilection to thrombosis are now recognized. Important behind stratifying risk of recurrent events is the necessity of correctly identifying hereditary thrombophilic disorders, especially in circumstances in which laboratory results, e.g., mildly low antithrombin III (ATIII) or protein S levels, may be more indicative of a temporary acquired deficiency. The relevance of thrombophilic testing is debated, but most clinicians agree that prothrombotic assessment should be considered in individuals with unprovoked thrombosis at age less than 40 years, individuals who have had thrombosis at an unusual anatomic site or who have had repeated thromboses, or when the family history suggests multiple affected individuals. For review of the laboratory assessment of thrombophilia see references [1][2][3] . The following discussion is not meant to be comprehensive, but serves to highlight a few of the clinical management decisions important in the care of the thrombophilic patient. Therapeutic considerations involving individuals with antiphospholipid syndrome (APS) will be included where pertinent. Duration of anticoagulant therapyThe decision to extend therapy beyond 6-12 months after an incident thrombotic event must be made on an individual basis. Patients with a transient risk factor such as oral contraceptive use, postsurgical state or limb immobilization have a low risk of recurrence of thrombosis once anticoagulation has been completed. (For review see 4,5 .) Identifying the individual with moderate to high risk of recurrent thrombosis is important to prevent the unnecessary risk of hemorrhage from long-term anticoagulation. From studies of patients with a first VTE (both with and without diagnosed hereditary thrombophilia), one third of patients with unprovoked VTE will have a reoccurrence over the next 10 years and 6% of patients with VTE develop postphlebitic syndrom...

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“…Only few studies provided data on the risk of recurrence in patients with multiple episodes of VTE [8][9][10][11]. In a prospective cohort study, Hansson et al found a 1.7 (95% CI 1.16,2.52) relative risk of recurrence in patients with more than one episode of DVT in comparison to patients with a first Letters V V C 2012 Wiley Periodicals, Inc.…”

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