einstein choice trial

Rivaroxaban reduced the relative risk of recurrence by about 70% in patients with both unprovoked and provoked venous thromboembolism. Prespecified objective testing was required for patients in whom an outcome event was suspected.22 Continuation of anticoagulant or antiplatelet therapy after study completion was at the discretion of the treating physician. Nephron 1976;16:31-41, 24. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439. It is not known whether the efficacy of this strategy extends to patients who receive less than 6 months of primary anticoagulant therapy, or whether more than 1 year of extended prophylaxis with rivaroxaban would continue to yield a similar risk/benefit ratio. J Thromb Haemost 2005;3:692-694, 26. Prins MH, Lensing AW, Bauersachs R, et al. Nonmajor bleeding that was associated with a study-drug interruption for more than 14 days occurred in 17 patients (1.5%) in the 20-mg rivaroxaban group and in 12 patients (1.1%) in the 10-mg rivaroxaban group, as compared with 12 patients (1.1%) in the aspirin group. 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). Cohen AT, Agnelli G, Anderson FA, et al. First, patients who required extended treatment with therapeutic doses of anticoagulant agents were excluded. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. Patients were excluded if they had a contraindication to continued anticoagulation including liver failure, renal failure, or required concurrent antiplatelet therapy. Fatal venous thromboembolism occurred in 2 patients (0.2%) who were receiving 20 mg of rivaroxaban, in no patients who were receiving 10 mg of rivaroxaban, and in 2 patients (0.2%) who were receiving aspirin (Table 2). The primary efficacy outcome was a composite of symptomatic, recurrent fatal or nonfatal venous thromboembolism and unexplained death for which pulmonary embolism could not be ruled out. A digital journal for innovative original research and fresh, bold ideas in clinical trial design and clinical decision-making. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2013;368:709-718, 9. The sponsor collected, maintained, and analyzed the data; the academic authors had access to the data at all times through the sponsor. What are the clinical implications of these findings? In patients with VTE who have completed 6-12 months of anticoagulation, does long-term rivaroxaban treatment reduce the rate of recurrent VTE compared to aspirin? Third, our study was not powered to show the noninferiority of the 10-mg dose of rivaroxaban to the established treatment regimen of 20 mg, so any conclusions with respect to this issue are speculative. Major bleeding occurred at a rate of 0.5% in patients receiving rivaroxaban 20 mg/d, in 0.4% receiving 10 mg/d, and in 0.3% of patients receiving aspirin. ); Hospital Beneficncia Portuguesa, So Paulo (B.B. Non-inferiority trial was not performed to show 10 mg/d is noninferior to the current treatment dose of 20 mg/d. In patients with an unprovoked DVT of the leg (isolated distal or proximal) or PE, we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration (Grade 1B), and we recommend treatment with anticoagulation for 3 months over treatment of a longer, time-limited period (eg, 6, 12, or 24 months) (Grade 1B). ); Centre dInvestigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Mdecine Vasculaire et Thrapeutique, Centre Hospitalo-Universitaire, Hpital Nord, Saint Etienne, France (H.D. For patients with PE secondary to a transient (reversible) risk factor, oral anticoagulation is recommended for 3 months (class I, level B). The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. The most advanced way to teach, practice, and assess clinical reasoning skills. Cockcroft DW, Gault MH. Oral rivaroxaban for symptomatic venous thromboembolism. From March 2014 through March 2016, a total of 3396 patients from 244 sites in 31 countries were enrolled. Konstantinides SV, et al. Therapy was initiated at least 24 hours following the last dose of therapeutic anticoagulation and was intended to continue for 12 months. In patients with DVT of the leg or PE and active cancer (cancer-associated thrombosis) and who (i) do not have a high bleeding risk, we recommend extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 1B), and (ii) have a high bleeding risk, we suggest extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 2B). N Engl J Med 2003;348:1425-1434, 7. The primary efficacy outcome was a composite of symptomatic, recurrent fatal or nonfatal venous thromboembolism and unexplained death for which pulmonary embolism could not be ruled out. In conclusion, we found that rivaroxaban, at both a treatment dose (20 mg) and a thromboprophylactic dose (10 mg), was more effective than aspirin for the prevention of recurrent venous thromboembolism among patients who were in equipoise for continued anticoagulation. The per-protocol population included all those in the intention-to-treat population with the exception of those who had a rate of adherence to the study-drug regimen of less than 80% or who had other major protocol violations. Figure 1 shows the random assignment and follow-up of the patients. Funding provided by Bayer Pharmaceuticals. Spencer FA, Gore JM, Lessard D, Douketis JD, Emery C, Goldberg RJ. N Engl J Med 2008;358:2776-2786, 21. ); Janssen Research and Development, Raritan, NJ (L.H. MMWR Morb Mortal Wkly Rep 2012;61:401-404, 4. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. 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.6,12-14. Prevention of recurrent pulmonary embolism is particularly important, because the case-fatality rate at 30 days is at least twice as high with pulmonary embolism as with deep-vein thrombosis.27. An association between atherosclerosis and venous thrombosis. Study drugs were administered for up to 12 months. In patients with a first VTE that is an unprovoked proximal DVT of the leg or PE and who have a (i) low or moderate bleeding risk (see text), we suggest extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy (Grade 2B), and a (ii) high bleeding risk (see text), we recommend 3 months of anticoagulant therapy over extended therapy (no scheduled stop date) (Grade 1B). This includes the ASPIRE and WARFASA trials of aspirin and the AMPLIFY-EXT trial of apixaban. Prediction of creatinine clearance from serum creatinine. Clinical strategies for extended anticoagulation in patients with venous thromboembolism are uncertain. Patients were randomized 1:1:1 to rivaroxaban 20 mg/d, rivaroxaban 10 mg/d, or aspirin 100 mg/d, and each group was provided with a matching placebo. Stay connected to what's important in medical research and clinical practice, Subscribe to the most trusted and influential source ofmedical knowledge. ), and Thrombosis Research Institute and University College London (A.K.K.) The first three authors wrote the first draft of the manuscript, and all the steering committee members contributed to subsequent versions, made the decision to submit the manuscript for publication, and vouch for the accuracy and completeness of the data and for the fidelity of the study to the protocol. Apixaban for extended treatment of venous thromboembolism. Information, resources, and support needed to approach rotations - and life as a resident. Brighton TA, Eikelboom JW, Mann K, et al. Becattini C, Agnelli G, Schenone A, et al. Patients with unprovoked venous thromboembolism are known to be at high risk for recurrence, but the risk of recurrence among those in whom venous thromboembolism was provoked by minor transient or persistent risk factors is less certain. Study lasted for 1 year, but did not look into whether continued treatment is necessary. Published in 2017, EINSTEIN-CHOICE enrolled patients who had completed 6-12 months of therapeutic anticoagulation for acute VTE, either provoked (~60%) or unprovoked (~40%). In each panel, the inset shows the same data on an enlarged y axis. Demographic and Clinical Characteristics of the Patients at Baseline. ); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.). Patients underwent assessment, either in the clinic or by telephone, at days 30, 90, 180, 270, and 360 and at 30 days after stopping the study medication. 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. DOI: 10.1056/NEJMoa1700518, Tap into groundbreaking research and clinically relevant insights. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Eur Heart J. Thromb Haemost 2007;98:756-764, 3. For patients with PE and cancer, LMWH should be considered for the first 3-6 months (class IIa, level B). KaplanMeier Rates of Recurrent Fatal or Nonfatal Venous Thromboembolism and Major Bleeding. Arch Intern Med 2008;168:425-430, March 30, 2017N Engl J Med 2017; 376:1211-1222 The lower risk of a recurrent event among the patients who received rivaroxaban was associated with a rate of bleeding similar to that with aspirin. Low-dose aspirin for preventing recurrent venous thromboembolism. Rates of Recurrent Venous Thromboembolism and Major Bleeding, According to Risk Profile and Duration of Anticoagulation before Randomization. Turpie AG, Lassen MR, Davidson BL, et al. Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism: rationale for and design of the EINSTEIN CHOICE study. The protocol (available with the full text of this article at NEJM.org) was approved by the institutional review board at each participating center. Dr. Weitz reports receiving consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Portola, and Pfizer; Drs. Patel MR, Mahaffey KW, Garg J, et al. The rates of death from any cause were 0.7% and 0.2% in the 20-mg and 10-mg rivaroxaban groups, respectively, as compared with 0.6% in the aspirin group. Venous thromboembolism in adult hospitalizations United States, 20072009. Therefore, it remains unknown whether the 10-mg dose of rivaroxaban would be sufficient to prevent recurrence in such patients. Kearon C, Akl EA, Ornelas J, et al. Therefore, we found that rivaroxaban was more effective than aspirin for the prevention of recurrent venous thromboembolism and was associated with a similar risk of bleeding. This page was last edited on 3 December 2017, at 22:35. Stratified randomization into groups with 1:1:1 ratio: Comparisons are rivaroxaban 20 mg/d vs. rivaroxaban 10 mg/d vs. aspirin 100 mg/d. We conducted a randomized, double-blind, phase 3 study comparing the efficacy and safety of two doses of rivaroxaban with those of aspirin for the extended treatment of venous thromboembolism for up to 1 year after the initial 6 to 12 months of therapy.22 The trial was sponsored by Bayer Pharmaceuticals. Lancet 2008;372:31-39, 20. Our study has several potential limitations. Second, in this study and in the previous trial comparing rivaroxaban with placebo for extended treatment of venous thromboembolism, therapy was given for up to 12 months. In patients who refuse to take or are unable to tolerate any form of oral anticoagulants, aspirin may be considered for extended secondary VTE prophylaxis (class IIb, level B). ), Venous thromboembolism, which includes deep-vein thrombosis and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke.1-3 The mainstay of treatment is anticoagulation,4 and in patients without active cancer, guidelines suggest the use of direct oral anticoagulant agents such as rivaroxaban over vitamin K antagonists such as warfarin.4 Anticoagulation therapy is administered for 3 months or longer, depending on the balance between the risk of recurrent venous thromboembolism and the risk of bleeding.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.5-9 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.11-13 Although extended anticoagulation therapy is effective for the prevention of recurrent venous thromboembolism,5-9 concern about bleeding often leads to a reluctance to continue anticoagulant treatment beyond 6 to 12 months. Although 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. The efficacy and safety analyses included all the patients who had undergone randomization with valid informed consent and who had received at least one dose of a study medication (intention-to-treat population). Thromb Haemost 2015;114:645-650, 23. 2014 Nov 14;35(43):3033-69. http://www.wikijournalclub.org/w/index.php?title=EINSTEIN_CHOICE&oldid=27712, In patients with DVT of the leg or PE and no cancer, as long-term (first 3months) anticoagulant therapy, dabigatran, rivaroxaban, apixaban, or edoxaban are recommended over vitamin K antagonist (VKA) therapy(all Grade 2B), In patients with DVT of the leg or PE and cancer (cancer-associated thrombosis), as long-term (first 3months) anticoagulant therapy, LMWH is recommended over other agents (Grade 2C), In patients with DVT of the leg or PE who receive extended therapy, recommend no need tochange the choice of anticoagulant after the first 3months (Grade 2C). A primary efficacy outcome event occurred in 17 of 1107 patients (1.5%) who were receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) who were receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) who were receiving aspirin. The majority of patients with provoked VTE can be treated with a limited course of anticoagulation therapy (e.g., 3-6 months) followed by therapy discontinuation. J Thromb Haemost 2015;13:2119-2126, 27. In 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. The incidence of adverse events was similar in all three groups. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. Peer-reviewed journal featuring in-depth articles to accelerate the transformation of health care delivery. With aspirin, the rate of recurrent venous thromboembolism was 3.6% among the patients in whom the index event was provoked (i.e., associated with a known event, such as surgery or hospital admission) and 5.6% among those in whom the index event was unprovoked (i.e., idiopathic) (Table 3). ); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B. For patients with unprovoked PE, oral anticoagulation is recommended for at least 3 months (class I, level A). The EINSTEINPE Investigators. NEW! No other potential conflict of interest relevant to this article was reported. Ann Intern Med 1996;125:1-7, 6. Valuable tools for building a rewarding career in health care. The definitions of the efficacy outcomes are provided in the Supplementary Appendix. All the members of the steering committee contributed to the interpretation of the results. Patients were assigned, in a 1:1:1 ratio, to receive 20 mg of rivaroxaban, 10 mg of rivaroxaban, or 100 mg of aspirin, all given once daily with food. In patients who have recurrent VTE on VKA therapy (in the therapeutic range) or on dabigatran, rivaroxaban, apixaban, or edoxaban (and are believed to be compliant), recommend switching totreatment with LMWH at least temporarily(Grade 2C). NEW! Weitz JI, et al. Agnelli G, Buller HR, Cohen A, et al. KaplanMeier curves were constructed to display the distribution of events over time. We determined that the occurrence of 80 primary efficacy outcome events would provide a power of 90% to show the superiority of each dose of rivaroxaban over aspirin (each at a two-sided alpha level of 0.05), assuming a relative risk reduction of 70% with 20 mg of rivaroxaban and of 60% with 10 mg of rivaroxaban.7 On the basis of an expected frequency of the primary efficacy outcome of 5.0% at 12 months with aspirin,12,13 we calculated that we would need to enroll 2850 patients. Schulman S, Kearon C, Kakkar AK, et al. Recurrent venous thromboembolism included fatal and nonfatal pulmonary embolism and deep-vein thrombosis. Figure 2A shows the time course of symptomatic fatal or nonfatal recurrent venous thromboembolism. The long-term clinical course of acute deep venous thrombosis. Prandoni P, Bilora F, Marchiori A, et al. In patients who receive extended anticoagulation, the risk-benefit ratio of continuing such treatment should be reassessed at regular intervals (class I, level C). Specific groups were underrepresented in this study, including those with active malignancy (~2.5% of enrolled patients) and those with known thrombophilia (~6-7%), and thus it is unknown whether this study's results can be extrapolated in these populations. KaplanMeier curves are shown for the first event of recurrent fatal or nonfatal venous thromboembolism during the individual intended treatment periods (Panel A) and for the first episode of major bleeding during the period between the administration of the first dose of a study drug and 48 hours after the administration of the last dose (Panel B). Clinically relevant nonmajor bleeding was defined as overt bleeding that did not meet the criteria for major bleeding but was associated with the need for medical intervention, unscheduled contact with a physician, interruption or discontinuation of the study drug, or discomfort or impairment of activities of daily living.26 (Further details regarding the criteria are provided in the Supplementary Appendix.). Kearon C et al. This article was published on March 18, 2017, at NEJM.org. Randomization with a block size of six was performed with the use of an interactive voice-response system and was stratified according to the index diagnosis (deep-vein thrombosis or pulmonary embolism) and country. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding. The EINSTEIN Investigators. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. The steering committee, which included both academic authors and those employed by the sponsor, had final responsibility for the design of the study, the development of the protocol, the oversight of the study, the verification of the data, and the analyses. In patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy and do not have a contraindication to aspirin, we suggest aspirin over no aspirin to prevent recurrent VTE (Grade 2B). Additional ineligibility criteria included a calculated creatinine clearance of less than 30 ml per minute23,24 or hepatic disease associated with a coagulopathy. Prandoni P, Lensing AW, Cogo A, et al. Among 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. 1. Kearon C, Ginsberg JS, Kovacs MJ, et al. In patients with a second unprovoked VTE and who have a (i) low bleeding risk (see text), we recommend extended anticoagulant therapy (no scheduled stop date) over 3 months (Grade 1B); (ii) moderate bleeding risk (see text), we suggest extended anticoagulant therapy over 3 months of therapy (Grade 2B); or (iii) high bleeding risk (see text), we suggest 3 months of anticoagulant therapy over extended therapy (no scheduled stop date) (Grade 2B). Similar results were found for the composite outcome of major or clinically relevant nonmajor bleeding. Both rivaroxaban doses were superior to aspirin with respect to the primary efficacy outcome (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). Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. Chest 2016;149:315-352, 5. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. Previous studies have shown that as compared with placebo, aspirin reduced the relative risk of recurrent venous thromboembolism by 32% (2.4 percentage points),12,13 whereas a 20-mg dose of rivaroxaban reduced the relative risk by 82% (6.8 percentage points).7 Consistent with those findings, our study shows that as compared with aspirin, both the 20-mg and 10-mg doses of rivaroxaban reduced the relative risk of recurrent venous thromboembolism by about 70% (approximately 3 percentage points). Patients were instructed to report to the study center if they had symptoms suggestive of recurrent venous thromboembolism or bleeding. Clinically relevant nonmajor bleeding was identified in 2.7% of patients receiving rivaroxaban 20 mg/d, in 2.0% of patients receiving 10 mg/d, and in 1.8% of patients receiving aspirin. Lassen MR, Ageno W, Borris LC, et al. The intention-to-treat population included all the patients who had undergone randomization with valid informed consent and who had received at least one dose of a study medication. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. A full list of inclusion and exclusion criteria is provided in the Supplementary Appendix, available at NEJM.org. Both rivaroxaban doses were superior to aspirin with respect to the primary efficacy outcome (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). Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Lancet 2009;373:1673-1680, 22. Extended oral anticoagulation should be considered for patients with a first episode of unprovoked PE and low bleeding risk (class IIa, level B). We found that patients with venous thromboembolism with ongoing risk factors have an appreciable risk of recurrence because even with aspirin, the rate of recurrent venous thromboembolism in such patients was 3.6%, as compared with a rate of recurrence of 5.6% in those with unprovoked venous thromboembolism. N Engl J Med 2012;367:1979-1987, 13. N Engl J Med 2011;365:883-891, 16. In patients without reversible risk factors for VTE, the risk of recurrent VTE remains elevated after 6-12 months of therapeutic anticoagulation, and extended-duration anticoagulation is often warranted. both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B. Written informed consent was obtained from all the patients. Levey AS, Stevens LA, Schmid CH, et al. ), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B. ), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B. Patients were enrolled at least 24 hours after they had received the last dose of a direct oral anticoagulant agent or, if they were receiving a vitamin K antagonist, when the international normalized ratio was 2.5 or lower. Consequently, additional studies are needed to determine the utility of continuing treatment for longer periods. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. The study was designed to test the hypothesis that each dose of rivaroxaban would be superior to aspirin with respect to the primary efficacy outcome. These benefits were observed with rates of major and clinically relevant nonmajor bleeding that were low and similar to those with aspirin. All the patients who stopped a study treatment earlier than scheduled were followed until the end of the intended treatment period. The study did not consider the financial toxicity associated with extended anticoagulant therapy; the cost of rivaroxaban might discourage prolonged courses of anti-coagulation with a novel anti-coagulant. Rates of recurrence in patients whose index events were provoked or unprovoked were lower in both the 20-mg rivaroxaban group (1.4% and 1.8%, respectively) and the 10-mg rivaroxaban group (0.9% and 1.5%, respectively) than in the aspirin group. At a dose of 20 mg once daily, rivaroxaban is effective for stroke prevention in patients with atrial fibrillation15 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.18-21 In the Reduced-dosed Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) trial,22 we compared the efficacy and safety of these two doses of rivaroxaban with those of aspirin in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was equipoise regarding the need for continued anticoagulation. ); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B. Efficacy and safety outcomes were analyzed with the use of a Cox proportional-hazards model, stratified according to the index diagnosis (deep-vein thrombosis or pulmonary embolism). all in London; the University of Washington School of Medicine, Seattle (B.L.D. The per-protocol population excluded patients who had a rate of adherence to the study-drug regimen of less than 80% or who had other major protocol violations. Clinically relevant nonmajor bleeding occurred in 30 patients (2.7%) in the 20-mg rivaroxaban group and in 22 patients (2.0%) in the 10-mg rivaroxaban group, as compared with 20 patients (1.8%) in the aspirin group (Table 4). The most trusted, influential source of new medical knowledge and clinical best practices in the world. The main conclusion of this study is that up to 1 year of rivaroxaban at a dose of either 20 mg/d or 10 mg/d is efficacious in preventing recurrent VTE in patients who have completed 6-12 months of primary anticoagulant therapy, and this approach is not associated with increased bleeding compared to aspirin 100 mg/d. ); the Department of Haematology and Oncology, Kings College London (J.B.-W.), the Department of Haematological Medicine, Guys and St. Thomas Hospitals, Kings College Hospital (A.T.C. This study included patients with both provoked and unprovoked venous thromboembolism for whom there was equipoise regarding the need for continued anticoagulation.