Original Article
Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism
N Engl J Med 2009; 361:2342-2352December 10, 2009
- Abstract
Background
The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism.
Methods
In a randomized, double-blind, noninferiority trial involving patients with acute venous thromboembolism who were initially given parenteral anticoagulation therapy for a median of 9 days (interquartile range, 8 to 11), we compared oral dabigatran, administered at a dose of 150 mg twice daily, with warfarin that was dose-adjusted to achieve an international normalized ratio of 2.0 to 3.0. The primary outcome was the 6-month incidence of recurrent symptomatic, objectively confirmed venous thromboembolism and related deaths. Safety end points included bleeding events, acute coronary syndromes, other adverse events, and results of liver-function tests.
Results
A total of 30 of the 1274 patients randomly assigned to receive dabigatran (2.4%), as compared with 27 of the 1265 patients randomly assigned to warfarin (2.1%), had recurrent venous thromboembolism; the difference in risk was 0.4 percentage points (95% confidence interval [CI], −0.8 to 1.5; P<0.001 for the prespecified noninferiority margin). The hazard ratio with dabigatran was 1.10 (95% CI, 0.65 to 1.84). Major bleeding episodes occurred in 20 patients assigned to dabigatran (1.6%) and in 24 patients assigned to warfarin (1.9%) (hazard ratio with dabigatran, 0.82; 95% CI, 0.45 to 1.48), and episodes of any bleeding were observed in 205 patients assigned to dabigatran (16.1%) and 277 patients assigned to warfarin (21.9%; hazard ratio with dabigatran, 0.71; 95% CI, 0.59 to 0.85). The numbers of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in the two groups. Adverse events leading to discontinuation of the study drug occurred in 9.0% of patients assigned to dabigatran and in 6.8% of patients assigned to warfarin (P=0.05).
Conclusions
For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring. (ClinicalTrials.gov number, NCT00291330.)
Media in This Article
Figure 1
Cumulative Risk of Recurrent Venous Thromboembolism or Related Death during 6 Months of Treatment among Patients Randomly Assigned to Dabigatran or Warfarin.Figure 2
Cumulative Risks of a First Event of Major Bleeding and of Any Bleeding among Patients Randomly Assigned to Dabigatran or Warfarin.Article Activity
- Article
Venous thromboembolism affects 1 to 2 adults per 1000 annually and is the third most common cause of vascular death after myocardial infarction and stroke.1,2 The current standard treatment is rapidly acting parenteral anticoagulation for 5 to 7 days followed by at least 3 months of treatment with a vitamin K antagonist.3 Treatment with a vitamin K antagonist requires frequent monitoring of the international normalized ratio (INR), and multiple interactions of vitamin K antagonists with foods and other drugs have been reported.4
Dabigatran etexilate (hereafter termed dabigatran) is an orally available, potent, direct inhibitor of thrombin. It is rapidly converted by ubiquitous esterases to the active drug, is administered in fixed doses without the need for coagulation monitoring, is excreted by the kidney, and has a half-life of 12 to 17 hours.5 Dabigatran has similar efficacy and safety to enoxaparin for the prevention of venous thromboembolism in patients who have had elective hip or knee arthroplasty.6,7 Recently, dabigatran, as compared with warfarin, was shown to have superior safety with equivalent efficacy (when it was administered at a dose of 110 mg twice daily), or superior efficacy with similar safety (when it was administered at a dose of 150 mg twice daily), for the prevention of stroke in patients with atrial fibrillation.8 We compared dabigatran, administered at a dose of 150 mg twice daily, with warfarin for the treatment of acute venous thromboembolism.
Methods
Study Design
In the RE-COVER study, a double-blind, double-dummy, randomized trial, we compared 6 months of treatment with dabigatran, at a fixed dose of 150 mg twice daily, with dose-adjusted warfarin therapy, after initial parenteral anticoagulation. The study was funded, designed, and conducted, and the data analyzed, by Boehringer Ingelheim in conjunction with the steering committee, whose members vouch for the accuracy and completeness of the data and the analyses in this report. The members of the steering committee wrote the manuscript and made the decision to submit it for publication.
Study Patients
Patients were recruited from 228 clinical centers in 29 countries. Patients 18 years of age or older who had acute, symptomatic, objectively verified proximal deep-vein thrombosis of the legs or pulmonary embolism and for whom 6 months of anticoagulant therapy was considered to be an appropriate treatment were potentially eligible. Exclusion criteria were duration of symptoms longer than 14 days, pulmonary embolism with hemodynamic instability or requiring thrombolytic therapy, another indication for warfarin therapy, recent unstable cardiovascular disease, a high risk of bleeding, liver disease with an aminotransferase level that was two times the local upper limit of the normal range, an estimated creatinine clearance of less than 30 ml per minute, a life expectancy of less than 6 months, a contraindication to heparin or to radiographic contrast material, pregnancy or risk of becoming pregnant, or a requirement for long-term antiplatelet therapy (≤100 mg of acetylsalicylic acid daily was acceptable). There were no weight restrictions. All patients provided written informed consent, and the institutional review board at each participating clinical center approved the study.
Random Assignment and Treatment
Before randomization, the diagnosis of venous thromboembolism was established with the use of compression ultrasonography or venography of leg veins and ventilation–perfusion lung scanning, angiography, or spiral computed tomography of pulmonary arteries. Additional baseline examination of the initially nonexamined leg or legs with the use of compression ultrasonography and, in case of symptomatic deep-vein thrombosis, examination of the pulmonary arteries with the use of perfusion lung scanning or spiral computed tomography were required to be performed within 72 hours after randomization. We used a computer-generated randomization scheme with variable block sizes, stratified according to presentation (pulmonary embolism or deep-vein thrombosis without symptomatic pulmonary embolism) and the presence or absence of active cancer. Staff members at the clinical centers called an interactive voice-response system that randomly assigned subjects to one of the supplied medication kits. The treatment-group assignment was concealed from all the investigators and their staff at the coordinating center and the clinical centers and from the clinical monitors.
Patients were assigned in a 1:1 ratio to receive a fixed dose of dabigatran (150 mg twice daily taken orally) or warfarin. Initial treatment with an approved parenteral anticoagulant (generally unfractionated heparin administered intravenously or low-molecular-weight heparin administered subcutaneously) was usually started before random assignment. Warfarin or a placebo that looked identical to warfarin was generally started on the day of random assignment and was adjusted to achieve an INR of 2.0 to 3.0 on a point-of-care coagulometer that was programmed, in conjunction with the randomization schedule, to yield either a true INR or a sham INR (“single-dummy phase”). Administration of dabigatran or a placebo that looked identical to dabigatran was initiated, and the parenteral anticoagulant was stopped, once the parenteral anticoagulant had been given for at least 5 days and the true or sham INR was recorded as 2.0 or higher on 2 consecutive days. The first dose of dabigatran was given within 2 hours before the time that the next dose of initial parenteral therapy would have been due or at the time of discontinuation of intravenous unfractionated heparin. Active dabigatran and warfarin-like placebo or active warfarin and dabigatran-like placebo were then given for 6 months (“double-dummy phase”).
Follow-up and Outcome Measures
Patients were assessed at 7 days and then monthly until 6 months and were told to contact their study site immediately if symptoms developed that were suggestive of venous thromboembolism or bleeding. An additional follow-up visit was scheduled for 30 days after completion of the study, unless the patient had discontinued the study drug before 6 months, had started open-label anticoagulant therapy, or had been enrolled in another trial. Symptoms suggestive of recurrent venous thromboembolism were evaluated with the use of the same diagnostic methods that had been used for the initial diagnosis. Bleeding was defined as major if it was clinically overt and if it was associated with a fall in the hemoglobin level of at least 20 g per liter, resulted in the need for transfusion of 2 or more units of red cells, involved a critical site, or was fatal.9 Less severe bleeding episodes were classified as minor and were subcategorized as clinically relevant bleeding (see the Supplementary Appendix, available with the full text of this article at NEJM.org) or nuisance bleeding. Other adverse events, results of liver-function tests and other laboratory measures, occurrence of acute coronary syndromes, and adherence (quantified by capsule counts) were routinely assessed. All suspected outcome events and deaths were classified by central adjudication committees, whose members were unaware of the treatment assignments.
Statistical Analysis
The trial was designed to determine whether 6 months of dabigatran therapy was as effective as 6 months of warfarin therapy (i.e., noninferior) and to compare the safety of the two treatments. The sample size was determined on the basis of an expected rate of the primary efficacy outcome of 2% at 6 months in each group and a requirement that the study would have 90% power to exclude a hazard ratio of 2.75 and an absolute increase in risk of 3.6 percentage points for the primary outcome with dabigatran, at a one-sided alpha level of 0.025. These noninferiority margins were estimated to correspond to preservation of 57% (for assessment of hazard ratio) and 75% (for assessment of difference in risk) of the lower boundary of the 95% confidence interval for the efficacy of warfarin as compared with no anticoagulation, as assessed in four studies that compared discontinuing warfarin therapy at 4 to 6 weeks with continuing it for 3 to 6 months.10-13 We anticipated that the data from up to 20% of the randomly assigned patients might not be able to be analyzed. A sample size of 2550 patients, with 1275 in each group, and an expected total of 46 events satisfied these requirements. No formal interim analyses were planned or performed. The data and safety monitoring board monitored safety and efficacy end points.
The primary analysis for efficacy was a comparison between the groups of the time to the first occurrence of the composite end point of symptomatic venous thromboembolism or death associated with venous thromboembolism in the 6 months after random assignment, as assessed by the hazard ratio calculated with the use of the Cox model and the difference in risk calculated with the use of Kaplan–Meier estimates. Both summary statistics were adjusted for the initial presentation (i.e., pulmonary embolism or deep-vein thrombosis) and for the presence or absence of active cancer at baseline (the interaction between active cancer and symptomatic pulmonary embolism was also included in the Cox model).
We tested for noninferiority by comparing the upper boundary of the 95% confidence interval for the hazard ratio with the predefined margin of 2.75 and the upper boundary of the 95% confidence interval for the difference in risk with the predefined margin of 3.6 percentage points. If noninferiority was established by both criteria, testing for superiority of dabigatran was to be performed.
We analyzed efficacy according to a modified intention-to-treat principle, since patients who did not receive any study drug were excluded from all analyses, as was prespecified in the protocol. For safety analyses, including bleeding episodes, events were considered from the time of the first intake of the study drug to 6 days after the last intake of the study drug; these analyses were performed on the basis of the patient's actual treatment with the study drug. The 6-day period after the last intake of the study drug was not included in the analysis if patients started open-label anticoagulant therapy or if they were enrolled in the RE-MEDY study (ClinicalTrials.gov number, NCT00329238), a double-blind trial comparing dabigatran and warfarin for extended treatment of venous thromboembolism. All safety analyses and secondary efficacy analyses were predefined.
Results
Patients
From April 2006 through November 2008, a total of 2564 patients were randomly assigned to a study group; 78.5% of the patients were from Europe or North America. Seven patients in the dabigatran group and 18 in the warfarin group did not receive any study medication (4 did not meet the inclusion criteria for venous thromboembolism, 11 met the exclusion criteria, 5 withdrew consent, 4 never took the study drug, and 1 had another reason). A total of 1274 patients in the dabigatran group and 1265 in the warfarin group were included in the analysis of efficacy. One patient who was assigned to receive dabigatran mistakenly received warfarin during the entire study; this patient did not have any outcome event and was included as part of the warfarin group in the safety analysis. There were no significant differences between the groups in baseline characteristics (Table 1Table 1
Characteristics of the Patients and Treatments.).Treatment and Follow-up
Parenteral anticoagulation was given for a mean of 10 days in both treatment groups. The details of the treatment given are shown in Table 1. The mean number of INR values obtained in the warfarin group over the course of 6 months was 16. The INR was in the therapeutic range 60% of the time (Table 1), improving from 53% during the first month to 66% during the last month. Overall, the INR was below the therapeutic range 21% of the time and above the therapeutic range 19% of the time. The study drug was stopped before 6 months in 204 patients (16.0%) in the dabigatran group (126 because of an adverse event, 21 because of nonadherence, 9 because of loss to follow-up, 39 because of withdrawal of consent, and 9 for other reasons) and in 183 patients (14.5%) in the warfarin group (102 because of an adverse event, 35 because of nonadherence, 6 because of loss to follow-up, 36 because of withdrawal of consent, and 4 for other reasons). The observation time for the assessment of efficacy was shorter than 6 months in 101 patients (7.9%) in the dabigatran group (47 because of an adverse event, 13 because of nonadherence, 16 because of loss to follow-up, 22 because of withdrawal of consent, and 3 for other reasons) and 97 patients (7.7%) in the warfarin group (40 because of an adverse event, 20 because of nonadherence, 11 because of loss to follow-up, 25 because of withdrawal of consent, and 1 for other reasons). Although it was intended that all patients who stopped the study drug owing to an adverse event or who were considered to show nonadherence would complete 6 months of follow-up, this did not always occur. After completion of 6 months in this trial, 506 patients in the dabigatran group and 541 patients in the warfarin group gave additional informed consent and were randomly assigned a second time to receive treatment with dabigatran or warfarin as extended secondary prophylaxis, as part of the double-blind RE-MEDY study.
Efficacy
The investigators suspected that recurrent venous thromboembolism had occurred or that a death had been related to recurrent venous thromboembolism in 134 patients in the dabigatran group and 130 patients in the warfarin group. After central adjudication, the primary outcome for efficacy was confirmed in 30 patients in the dabigatran group (2.4% of all patients in the dabigatran group) and 27 patients in the warfarin group (2.1% of all patients in the warfarin group). The difference in risk was 0.4 percentage points (95% confidence interval [CI], −0.8 to 1.5; hazard ratio, 1.10; 95% CI, 0.65 to 1.84) (Figure 1Figure 1
Cumulative Risk of Recurrent Venous Thromboembolism or Related Death during 6 Months of Treatment among Patients Randomly Assigned to Dabigatran or Warfarin.). As compared with warfarin, dabigatran was noninferior with regard to the prevention of recurrent or fatal venous thromboembolism (P<0.001 for the criteria of both hazard ratio and the difference in risk). The results for the components of the primary end point are shown in Table 2Table 2
Efficacy and Bleeding Outcomes.. There was no significant difference in efficacy in predefined subgroups (see the Supplementary Appendix). Since noninferiority was established, we tested for superiority and found that it was not reached.Safety
A total of 20 patients in the dabigatran group (1.6%) and 24 patients in the warfarin group (1.9%), had major bleeding episodes (hazard ratio, 0.82; 95% CI, 0.45 to 1.48) (Figure 2Figure 2
Cumulative Risks of a First Event of Major Bleeding and of Any Bleeding among Patients Randomly Assigned to Dabigatran or Warfarin.). The sites of major bleeding events in the dabigatran group were gastrointestinal (nine events), urogenital (five), intraarticular (one), intramuscular (one), or other (six), and the sites in the warfarin group were urogenital (six events), gastrointestinal (five), intraarticular (four), intracranial (three), intramuscular (three), or other (four); some patients had bleeding at more than one site. INR values were not obtained when bleeding occurred, in order to avoid unblinding of the treatment assignment. A total of 71 patients in the dabigatran group (5.6%), as compared with 111 in the warfarin group (8.8%), had major or clinically relevant nonmajor bleeding (hazard ratio, 0.63; 95% CI, 0.47 to 0.84; P=0.002). The relative risk of bleeding with dabigatran as compared with warfarin was similar among the subgroups (data not shown). The only type of bleeding that showed a trend to higher incidence in the dabigatran group was gastrointestinal hemorrhage (Table 2).There were 115 patients in the dabigatran group (9.0%) and 86 patients in the warfarin group (6.8%) who had an adverse event that led to discontinuation of the study drug (hazard ratio, 1.33; 95% CI, 1.01 to 1.76; P=0.05). The number of patients who died, had an acute coronary syndrome, or had an elevation of the alanine aminotransferase level or the aspartate aminotransferase level exceeding three times the upper limit of normal while taking the study drug did not differ significantly between the treatment groups (Table 3Table 3
Adverse Events during the Double-Dummy Phase and during the Total Period of Treatment.). A combination of an alanine aminotransferase level exceeding three times the upper limit of normal and bilirubin exceeding twice the upper limit of normal was seen in two patients in the dabigatran group (of whom one had pancreatic cancer and the other had cholangitis) and four patients in the warfarin group (of whom three had pancreatic cancer and one had uterine cancer with liver metastases). There were no significant differences between the two treatment groups in the frequency of any adverse events (Table 3) except for dyspepsia (2.9% in the dabigatran group vs. 0.6% in the warfarin group, P<0.001).Discussion
In this large, double-blind trial involving patients with acute venous thromboembolism, we compared 6 months of treatment with dabigatran, administered at a dose of 150 mg twice daily, with warfarin therapy, after initial treatment with parenteral anticoagulation. We showed that dabigatran is noninferior to warfarin (when warfarin is dose-adjusted to achieve and maintain an INR in the range of 2.0 to 3.0) in the prevention of recurrent events. Venous thromboembolism or related deaths occurred in 30 patients in the dabigatran group as compared with 27 patients in the warfarin group.
Dabigatran is an effective anticoagulant agent because direct thrombin inhibitors suppress thrombus growth by inhibiting both fibrin-bound and free thrombin, which converts fibrinogen to fibrin.14 In the RE-COVER study, treatment with dabigatran was as effective as warfarin therapy, which achieved INR values within the therapeutic INR range 60% of the time — a rate that is consistent with good-quality management of warfarin dosing.15
The rates of bleeding with dabigatran were similar to or lower than those with warfarin. There were 20 major bleeding events in the dabigatran group as compared with 24 in the warfarin group, and there were fewer episodes of nonmajor bleeding with dabigatran than with warfarin. These findings are consistent with data on bleeding from the Randomized Evaluation of Long-Term Anticoagulation Therapy trial (RE-LY; NCT00262600),8 in which open-label dabigatran and warfarin therapies were compared in patients with atrial fibrillation. In the RE-LY trial, major bleeding and intracranial bleeding were less frequent among patients receiving dabigatran (at a dose of 150 mg twice daily) than among those receiving warfarin, and in both the RE-LY trial and the current study, the incidence of nonmajor bleeding was reduced with dabigatran. Clinically relevant nonmajor bleeding is an important factor to consider, since its management is time-consuming and costly16 and since bleeding is the most important reason for the perception of decreased health and quality of life among patients treated with warfarin.17
In trials of the only previously available oral direct thrombin inhibitor, ximelagatran, noninferiority with respect to warfarin was achieved in the treatment of recurrent venous thromboembolism, and rates of major bleeding were similar in both treatment groups.18 However, toxic effects to the liver occurred with prolonged exposure to ximelagatran.19 In contrast, there was no evidence of hepatic toxic events associated with dabigatran in the current study or in studies in which it was used for other indications.7,8,20 Dyspepsia, which was observed in 3% of the patients in the dabigatran group, was the only adverse event attributable to dabigatran in our study. The mechanism for increased dyspepsia among patients receiving dabigatran therapy is currently unknown. None of the other adverse events differed significantly between the treatments.
In the current study, the average age of the patients was 55 years, more than 90% had a creatinine clearance that was higher than 50 ml per minute, and 95% of the study population was white. Therefore, additional studies should be performed that involve patients whose baseline characteristics differ markedly from this population. A limitation of the study is that the first dose of dabigatran, which has a rapid onset of effect, was given only after initial parenteral anticoagulation therapy had been administered for a median of 9 days (interquartile range, 8 to 11). Thus, there are no data to support the use of dabigatran monotherapy for acute venous thromboembolism. We chose to treat patients in the dabigatran group with initial parenteral anticoagulation, because treatment of acute venous thromboembolism with ximelagatran alone appeared to be associated with a higher early rate of recurrent venous thromboembolism than did treatment with enoxaparin and warfarin.18 The median total duration of parenteral therapy of 9 days is longer than the typical duration of treatment when warfarin and heparin are started simultaneously; however, the duration of heparin therapy (5 days as compared with 10 days) has not been shown to influence the efficacy of long-term anticoagulation.21,22
Our trial provides data to support dabigatran as a fixed-dose oral treatment for acute deep-vein thrombosis and pulmonary embolism. For patients and health care providers, dabigatran is a far more convenient drug than warfarin because it has no known interactions with foods and minimal interactions with other drugs and therefore does not require routine blood-coagulation testing.
Supported by Boehringer Ingelheim.
Dr. Schulman reports receiving consulting fees from AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi-Aventis, lecture fees from LEO Pharma, Sanofi-Aventis, and Boehringer Ingelheim, and grant support from Bayer HealthCare; Dr. Kearon, consulting fees from Boehringer Ingelheim; Dr. Kakkar, consulting fees and honoraria from Boehringer Ingelheim, Bayer Schering Pharma, Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, ARYx Therapeutics, Canyon Pharmaceuticals, and Eisai, lecture fees from Sanofi-Aventis, Bayer Schering Pharma, Boehringer Ingelheim, GlaxoSmithKline, Eisai, and Pfizer, and grant support from Sanofi-Aventis, Boehringer Ingelheim, Pfizer, and Bayer Schering Pharma; Dr. Mismetti, consulting fees and lecture fees from Boehringer Ingelheim, Sanofi-Aventis, and GlaxoSmithKline; Dr. Schellong, lecture fees and consulting fees from Bayer HealthCare, Boehringer Ingelheim, and GlaxoSmithKline and consulting fees from Sanofi-Aventis; Dr. Eriksson, consulting fees and lecture fees from Boehringer Ingelheim, Pfizer, AstraZeneca, Bayer HealthCare, LEO Pharma, and Sanofi-Aventis; and Dr. Goldhaber, clinical research support from Sanofi-Aventis, Bristol-Myers Squibb, and Boehringer Ingelheim, and consulting fees from Sanofi-Aventis, Boehringer Ingelheim, Merck, MEDRAD Interventional/Possis, Bristol-Myers Squibb, Genentech, and Medscape. Mr. Baanstra and Dr. Schnee report being employees of Boehringer Ingelheim. No other potential conflict of interest relevant to this article was reported.
This article (10.1056/NEJMoa0906598) was published on December 6, 2009, at NEJM.org.
Source Information
From the Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, ON, Canada (S. Schulman, C.K.); the Department of Hematology, Karolinska University Hospital, Stockholm (S. Schulman); Thrombosis Research Institute and Queen Mary University of London, London (A.K.K.); the Department of Vascular Pathology, Bellevue Hospital, Saint Etienne, France (P.M.); Medical Division 2, Municipal Hospital Friedrichstadt, Dresden, Germany (S. Schellong); the Department of Medicine, Sahlgrenska University Hospital-Östra, Gothenburg, Sweden (H.E.); Clinical Research, Boehringer Ingelheim, Alkmaar, the Netherlands (D.B.); Boehringer Ingelheim, Ridgefield, CT (J.S.); and Brigham and Women's Hospital, Harvard Medical School, Boston (S.Z.G.).
Address reprint requests to Dr. Schulman at Thrombosis Service, HHS-General Hospital, 237 Barton St. East, Hamilton, ON L8L 2X2, Canada, or at schulms@mcmaster.ca.
Members of the RE-COVER Study Group are listed in the Appendix.
Appendix
Members of the RE-COVER Study Group are as follows: Steering Committee: S. Schulman (chair), H. Eriksson, S. Goldhaber, A. Kakkar, C. Kearon, P. Mismetti, S. Schellong. Data and Safety Monitoring Board: E. Minar (chair), D. Bergqvist, J. Tijssen. Independent Central Adjudication Committee for venous thromboembolism, bleeding and death: M. Prins (chair), H. Büller, J. Otten. Acute Coronary Syndrome Adjudication Committee: M. Prins (chair), R. Peters, M. Mac Gillavry, H. Büller. Hepatology Review Panel: S. Pol (chair), A. Burroughs, I. Gilmore. Principal Investigators: Argentina: J. Bluguermann, O. Carlevaro, L. Dipaola, P. Gitelman, D. Santos, P. Schygiel; Australia: R. Baker, P. Blombery, A. Gallus, E. Gan, H. Gibbs, H. Salem; Austria: M. Baghestanian, E. Pilger, W. Sturm; Belgium: E. Debing, A. Gadisseur, P. Hainaut, P. Verhamme, J.-C. Wautrecht, M. Zicot; Brazil: J.M. Annichino Bizzachi, G. Araujo, J. Dalmo De Araujo, F.M. Duarte Brandão Panico, Y. Nagato, A.H. Pereira, P. Puech Leao, E. Ramaciotti, R.C. Rocha Moreira, J. Timi; Canada: D. Anderson, M. Crowther, S. Dolan, J. Eikelboom, F. Spencer, M. Game, S. Kahn, J. Kassis, C. Kearon, P. Klinke, M. Kovacs, A. Milot, B. Ritchie, M. Rodger, S. Solymoss, J. Villeneuve, E. Yeo; Czech Republic: P. Cervinka, M. Homza, P. Hrdy, Z. Klimsa, P. Lang, R. Maly, I. Oral, P. Reichert, J. Spinar, P. Varejka, J. Vladimir; Denmark: J. Brønnum-Schou, S. Jensen, S.E. Jensen, K.S. Kristensen, H. Nielsen, O. Wiemann; France: V. Bost, A. Buchmuller, K. Guillot, P. Laurent, F. Lecomte, D. Mottier, I. Quere, D. Wahl; Germany: J. Beyer, A. Dormann, U. Hoffmann, M. Maier, A. Mietaschk, S. Schellong; Greece: K. Katsenis, C. Klonaris, C. Liappis; Hungary: G. Acsady, I. Berhes, Z. Boda, K. Farkas, J. Jakucs, L. Kollar, L. Matyas, M. Riba, M. Sereg; India: R. Aggarwal, D. Banker, A. Bharani, M. Gadkari, J. Hiremath, A. Jain, S. Kareem, S. Lyengar, R. Parakh, N. Sekar, A. Srinivas, K. Suresh, T. Vujay; Israel: B. Brenner, S. Efrati, M. Elias, D. Gavish, E. Grossman, M. Lahav, M. Lishner, D. Zeltser; Italy: G. Agnelli, C. Cimminiello, G. Palareti, P. Prandoni, M. Santonastaso, M. Silingardi; Mexico: E. Aldrett Lee, J.M. Fontes Andrade, J. Jaurrieta Valles; the Netherlands: D. Biesma, A. Dees, R. Fijnheer, K. Hamulyak, M.H.H. Kramer, F.W.G. Leebeek, L. Lieverse, M.T. Nurmohamed; New Zealand: S. Chunilal, S. Jackson, P. Ockelford, M. Smith; Norway: A.M. Njaastad, P.M. Sandseth, A. Tveit, A. Waage; Portugal: J. Barata, M. Capitao, F.E. Fernandes, A. Leitão, L. Providência; Russia: D.I. Alohin, S. Belentsov, M. Chernyatina, A. Chernyavsky, A. Fokin, A. Gubenko, V. Alexander V. Guz, I. Katelnitsky, I. Katelnitsky, A.A.A. Khamitov, A. Khitaryan, G. Khubulava, I. Mikhailov, V. Shkurin, I. Staroverov, A. Tchumakov, A. Zaporozhsky; Slovakia: T. Duris, P. Poliacik, V. Spisak, M. Szentivanyi, V. Zubek; South Africa: D. Adler, D. Kelbe, D. Le Roux, A. Pieterse, R. Routier, R. Siebert, B. Sloane, C. Smith, H. Van Rensburg; Spain: J. Del Toro, M.J. García-Fuster, J. Mateo, M. Monreal, J.A. Nieto, P. Sánchez-Molini, C. Sedano, J. Trujillo, R. Valle, J. Villalta; Sweden: J. Aagesen, A. Carlsson, H. Eriksson, L. Johansson, G. Lärfars, P. Lindmarker, U. Säfvenberg, A. Själander; Turkey: U. Bengisun, T. Calkavur, M.R. Guney, S. Karahan, M. Kurtoglu, U. Sakinci; Ukraine: A. Gubka, V. Mishalov, O. Skupyy; United Kingdom: A. Cohen, D. Keeling, P. Kesteven, P. MacCallum, R. Maclean, P. Shah, H. Watson; United States: A. Bartkowiak, E. Bolster, W.C. Botnick, B. Burnett, A. Chervu, A.J. Comerota, N.M. Dy, F.A. Fulco, J.R. Gossage, S. Kaatz, B. Lahiri, R.G. Lerner, J.A. Masson, S. Moll, M. Morganroth, K. Patel, R. Paulson, R. Powell, R. Samson, A. Seibert, A. Spyropoulos, P.S. Vrooman, Jr.
- References
References
1
Oger E . Incidence of venous thromboembolism: a community-based study in Western France. Thromb Haemost 2000;83:657-660
Web of Science | Medline2
Spencer FA ,Emery C ,Lessard D , et al. The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med 2006;21:722-727
CrossRef | Web of Science | Medline3
Kearon C ,Kahn SR ,Agnelli G ,Goldhaber S ,Raskob GE ,Comerota AJ . Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:Suppl:454S-545S
CrossRef | Web of Science | Medline4
Ansell J ,Hirsh J ,Hylek E ,Jacobson A ,Crowther M ,Palareti G . Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:Suppl:160S-198S
CrossRef | Web of Science | Medline5
Baetz BE ,Spinler SA . Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases. Pharmacotherapy 2008;28:1354-1373
CrossRef | Web of Science | Medline6
Eriksson BI ,Dahl OE ,Rosencher N , et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007;5:2178-2185
CrossRef | Web of Science | Medline7
Eriksson BI ,Dahl OE ,Rosencher N , et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007;370:949-956
CrossRef | Web of Science | Medline8
Connolly SJ ,Ezekowitz MD ,Yusuf S , et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-1151
Full Text | Web of Science | Medline9
Schulman S ,Kearon C . Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005;3:692-694
CrossRef | Web of Science | Medline10
Holmgren K ,Andersson G ,Fagrell B , et al. One-month versus six-month therapy with oral anticoagulants after symptomatic deep vein thrombosis. Acta Med Scand 1985;218:279-284
CrossRef | Web of Science | Medline11
Levine MN ,Hirsh J ,Gent M , et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995;74:606-611
Web of Science | Medline12
Schulman S ,Lockner D ,Juhlin-Dannfelt A . The duration of oral anticoagulation after deep vein thrombosis: a randomized study. Acta Med Scand 1985;217:547-552
CrossRef | Web of Science | Medline13
Schulman S ,Rhedin AS ,Lindmarker P , et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995;332:1661-1665
Full Text | Web of Science | Medline14
Gross PL ,Weitz JI . New antithrombotic drugs. Clin Pharmacol Ther 2009;86:139-146
CrossRef | Web of Science | Medline15
Rose AJ ,Ozonoff A ,Henault LE ,Hylek EM . Warfarin for atrial fibrillation in community-based practise. J Thromb Haemost 2008;6:1647-1654
CrossRef | Web of Science | Medline16
Gould MK ,Dembitzer AD ,Sanders GD ,Garber AM . Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis: a cost-effectiveness analysis. Ann Intern Med 1999;130:789-799
Web of Science | Medline17
Lancaster TR ,Singer DE ,Sheehan MA , et al. The impact of long-term warfarin therapy on quality of life: evidence from a randomized trial. Arch Intern Med 1991;151:1944-1949
CrossRef | Web of Science | Medline18
Fiessinger JN ,Huisman MV ,Davidson BL , et al. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA 2005;293:681-689
CrossRef | Web of Science | Medline19
Schulman S ,Wahlander K ,Lundstrom T ,Clason SB ,Eriksson H . Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med 2003;349:1713-1721
Full Text | Web of Science | Medline20
Ezekowitz MD ,Reilly PA ,Nehmiz G , et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol 2007;100:1419-1426
CrossRef | Web of Science | Medline21
Gallus A ,Jackaman J ,Tillett J ,Mills W ,Wycherley A . Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism. Lancet 1986;2:1293-1296
CrossRef | Web of Science | Medline22
Hull RD ,Raskob GE ,Rosenbloom D , et al. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. N Engl J Med 1990;322:1260-1264
Full Text | Web of Science | Medline
- Citing Articles (157)
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1
Jawed Fareed, Indermohan Thethi, Debra Hoppensteadt. (2012) Old Versus New Oral Anticoagulants: Focus on Pharmacology. Annual Review of Pharmacology and Toxicology 52:1, 79-99
CrossRef2
William M. Weightman, Neville M. Gibbs. (2012) Management of coagulation. Current Opinion in Anaesthesiology 25:1, 86-95
CrossRef3
Christian Weimar, Stefan H. Hohnloser, John W. Eikelboom, Hans-Christoph Diener. (2012) Preventing Cardioembolic Stroke in Atrial Fibrillation with Dabigatran. Current Neurology and Neuroscience Reports 12:1, 17-23
CrossRef4
Nadia Rosencher, Pierre Albaladejo. (2012) A new approach with anticoagulant development: tailoring anticoagulant therapy with dabigatran etexilate according to patient risk. Expert Opinion on Pharmacotherapy 13:2, 217-226
CrossRef5
Alexander G.G. Turpie. (2012) Rivaroxaban for the prevention and treatment of venous thromboembolism. Fundamental & Clinical Pharmacology 26:1, 33-38
CrossRef6
Rupert M. Bauersachs. (2012) Use of anticoagulants in elderly patients. Thrombosis Research 129:2, 107-115
CrossRef7
Andreas Clemens, Joanne Ryn, Regina Sennewald, Norio Yamamura, Joachim Stangier, Martin Feuring, Sebastian Härtter. (2012) Switching from enoxaparin to dabigatran etexilate: pharmacokinetics, pharmacodynamics, and safety profile. European Journal of Clinical Pharmacology
CrossRef8
Daniel A. Bachovchin, Benjamin F. Cravatt. (2012) The pharmacological landscape and therapeutic potential of serine hydrolases. Nature Reviews Drug Discovery 11:1, 52-68
CrossRef9
Joyce S Balami, Alastair M Buchan. (2012) Complications of intracerebral haemorrhage. The Lancet Neurology 11:1, 101-118
CrossRef10
Ralph A.H. Stewart, Heather Astell, Laura Young, Harvey D. White. (2012) Thrombosis on a Mechanical Aortic Valve whilst Anti-coagulated With Dabigatran. Heart, Lung and Circulation 21:1, 53-55
CrossRef11
Job Harenberg, Svetlana Marx, Martin Krejczy, Martin Wehling. (2012) New anticoagulants - promising and failed developments. British Journal of Pharmacology 165:2, 363-372
CrossRef12
Cecilia Becattini, Maria Cristina Vedovati, Giancarlo Agnelli. (2012) Old and new oral anticoagulants for venous thromboembolism and atrial fibrillation: A review of the literature. Thrombosis Research
CrossRef13
Ferran García-Bragado Dalmau. (2012) La medicina actual ante los anticoagulantes de nueva generación. Medicina Clínica
CrossRef14
F. A. Ofosu. (2012) A review of the two major regulatory pathways for non-proprietary low-molecular-weight heparins. Thrombosis and Haemostasis 107:2,
CrossRef15
S. Härtter, N. Yamamura, J. Stangier, P. A. Reilly, A. Clemens. (2012) Pharmacokinetics and pharmacodynamics in Japanese and Caucasian subjects after oral administration of dabigatran etexilate. Thrombosis and Haemostasis 107:2,
CrossRef16
James H. Lewis, David E. Kleiner. 2012. Hepatic injury due to drugs, herbal compounds, chemicals and toxins. , 645-760.
CrossRef17
Harry R Büller, Alex S Gallus, Gerard Pillion, Martin H Prins, Gary E Raskob. (2012) Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, double-dummy, non-inferiority trial. The Lancet 379:9811, 123-129
CrossRef18
John W Eikelboom, Jeffrey I Weitz. (2012) Idrabiotaparinux treatment for venous thromboembolism. The Lancet 379:9811, 96-98
CrossRef19
Paolo Prandoni. (2012) Healthcare burden associated with the post-thrombotic syndrome and potential impact of the new oral anticoagulants. European Journal of Haematologyno-no
CrossRef20
Elie A Akl, Andrew D Oxman, Jeph Herrin, Gunn E Vist, Irene Terrenato, Francesca Sperati, Cecilia Costiniuk, Diana Blank, Holger Schünemann, Holger Schünemann. 2011. Framing of health information messages. .
CrossRef21
John G.T. Augoustides. (2011) Advances in Anticoagulation: Focus on Dabigatran, an Oral Direct Thrombin Inhibitor. Journal of Cardiothoracic and Vascular Anesthesia 25:6, 1208-1212
CrossRef22
Pierre Sié, Charles M. Samama, Anne Godier, Nadia Rosencher, Annick Steib, Juan V. Llau, Philippe Van der Linden, Gilles Pernod, Thomas Lecompte, Isabelle Gouin-Thibault, Pierre Albaladejo. (2011) Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: Thrombin or factor-Xa inhibitors. Recommendations of the Working Group on perioperative haemostasis and the French Study Group on thrombosis and haemostasis. Archives of Cardiovascular Diseases 104:12, 669-676
CrossRef23
I. Lazareth, P. Priollet. (2011) Actualités du 45e Congrès du Collège Français de Pathologie Vasculaire (CFPV) Paris, 16–18 mars 2011. Journal des Maladies Vasculaires 36, S1-S9
CrossRef24
Elise S. Eerenberg, Josien van Es, Meertien K. Sijpkens, Harry R. Büller, Pieter W. Kamphuisen. (2011) New anticoagulants: Moving on from scientific results to clinical implementation. Annals of Medicine 43:8, 606-616
CrossRef25
S. Combe, H.-R. Büller. (2011) Nouveaux traitements de la maladie thrombo-embolique veineuse. Journal des Maladies Vasculaires 36, S16-S19
CrossRef26
Ann K Wittkowsky. (2011) Novel Oral Anticoagulants and Their Role in Clinical Practice. Pharmacotherapy 31:12, 1175-1191
CrossRef27
L. Drouet, I. Mahé, G. Le Gal, M. Righini, I. Quéré. (2011) Thrombose – nouveaux anticoagulants en 2012. La Revue de Médecine Interne 32, S236-S240
CrossRef28
Juan Francisco Sanchez Muñoz-Torrero, Henri Bounameaux, José María Pedrajas, Alicia Lorenzo, Silvino Rubio, Clive Kearon, Luís Hernández, Manuel Monreal. (2011) Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis. Journal of Vascular Surgery 54:6, 26S-32S
CrossRef29
Michael Ganetsky, Kavita M. Babu, Steven D. Salhanick, Robert S. Brown, Edward W. Boyer. (2011) Dabigatran: Review of Pharmacology and Management of Bleeding Complications of This Novel Oral Anticoagulant. Journal of Medical Toxicology 7:4, 281-287
CrossRef30
Pamala Kanagasabapathy, Pratima Chowdary, Alex Gatt. (2011) Alternatives to Warfarin-The Next Generation of Anticoagulants. Cardiovascular Therapeutics 29:6, e80-e88
CrossRef31
Stavros Apostolakis, Gregory YH Lip, Deirdre A Lane, Eduard Shantsila. (2011) The Quest for New Anticoagulants: From Clinical Development to Clinical Practice. Cardiovascular Therapeutics 29:6, e12-e22
CrossRef32
H Reikvam, R V Tiu. (2011) Venous thromboembolism in patients with essential thrombocythemia and polycythemia vera. Leukemia
CrossRef33
J. BEYER-WESTENDORF, H. BÜLLER. (2011) External and internal validity of open label or double-blind trials in oral anticoagulation: better, worse or just different?. Journal of Thrombosis and Haemostasis 9:11, 2153-2158
CrossRef34
James M. Hunt, Todd M. Bull. (2011) Clinical Review of Pulmonary Embolism: Diagnosis, Prognosis, and Treatment. Medical Clinics of North America 95:6, 1203-1222
CrossRef35
S.M. Schellong. (2011) Therapie der Beinvenenthrombose und der Lungenembolie. Der Internist 52:11, 1284-1291
CrossRef36
Benjamin Kloesel, Roger F.J. Shepherd. (2011) 80-Year-Old Man With Massive Leg Swelling. Mayo Clinic Proceedings 86:11, 1109-1112
CrossRef37
Lucile Jeanne. (2011) Faut-il surveiller les nouveaux anticoagulants oraux ? Exemple du dabigatran. Option/Bio 22:462, 18-19
CrossRef38
K. Heidinger, B. Kemkes-Matthes. (2011) Neue Antithrombotika. Medizinische Klinik 106:3, 198-204
CrossRef39
K SCHREIBER, O ATEKA-BARRUTIA, MA KHAMASHTA, GRV HUGHES. (2011) OBSTETRIC ANTIPHOSPHOLIPID SYNDROME - A REVIEW. Fetal and Maternal Medicine Review 22:04, 265-286
CrossRef40
Paul Alexander Kyrle, Sabine Eichinger. (2011) Vitamin K antagonists: self-determination by self-monitoring?. The Lancet
CrossRef41
Rashid S. Kazmi, Bashir A. Lwaleed. (2011) New anticoagulants: how to deal with treatment failure and bleeding complications. British Journal of Clinical Pharmacology 72:4, 593-603
CrossRef42
Jignesh P. Patel, Lara N. Roberts, Roopen Arya. (2011) Anticoagulating obese patients in the modern era. British Journal of Haematology 155:2, 137-149
CrossRef43
Job Harenberg, Martin Wehling. (2011) Future of Anticoagulant Therapy. Cardiovascular Therapeutics 29:5, 291-300
CrossRef44
Vinai C. Bhagirath, Lauren O'Malley, Mark A. Crowther. (2011) Management of Bleeding Complications in the Anticoagulated Patient. Seminars in Hematology 48:4, 285-294
CrossRef45
Catherine J. Lee, Jack E. Ansell. (2011) Direct thrombin inhibitors. British Journal of Clinical Pharmacology 72:4, 581-592
CrossRef46
G. Meyer. (2011) À la recherche de la molécule idéale. Une brève histoire des anticoagulants. Revue des Maladies Respiratoires 28:8, 951-953
CrossRef47
L. Bertoletti, P. Mismetti. (2011) Les nouveaux anticoagulants dans la maladie thrombo-embolique veineuse. Revue des Maladies Respiratoires 28:8, 1008-1016
CrossRef48
Timothy K. Liem, Thomas G. DeLoughery. (2011) Direct Thrombin Inhibitors for the Treatment of Venous Thromboembolism: Analysis of the Dabigatran versus Warfarin Clinical Trial. Seminars in Vascular Surgery 24:3, 157-161
CrossRef49
P. Sié, C.-M. Samama, A. Godier, N. Rosencher, A. Steib, J.-V. Llau, P. van der Linden, G. Pernod, T. Lecompte, I. Gouin-Thibault, P. Albaladejo. (2011) Chirurgies et actes invasifs chez les patients traités au long cours par un anticoagulant oral anti-IIa ou anti-Xa direct. Annales Françaises d'Anesthésie et de Réanimation 30:9, 645-650
CrossRef50
Benjamin Brenner, Ron Hoffman. (2011) Emerging options in the treatment of deep vein thrombosis and pulmonary embolism. Blood Reviews 25:5, 215-221
CrossRef51
Prabashni Reddy, Julie K. Atay, Leslie G. Selbovitz, Jean Marie Connors, Gregory Piazza, Caroline Cole Block, Paul A. Arpino, Nancy Berliner, Adolph M. Hutter, Michael A. Fischer, David Kuter, James Weitzman, Geoffery K. Sherwood, Avraham Almozlino, Robert P. Giugliano. (2011) Dabigatran. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 10:3, 117-127
CrossRef52
T.S. Dharmarajan, Ankur Gupta, Mahadi A. Baig, Edward P. Norkus. (2011) Warfarin: Implementing Its Safe Use in Hospitalized Patients from Nursing Homes and Community Through a Performance Improvement Initiative. Journal of the American Medical Directors Association 12:7, 518-523
CrossRef53
C. Christersson, J. Oldgren, L. Wallentin, A. Siegbahn. (2011) Treatment with an oral direct thrombin inhibitor decreases platelet activity but increases markers of inflammation in patients with myocardial infarction. Journal of Internal Medicine 270:3, 215-223
CrossRef54
Hayan Moualla, David Garcia. (2011) Vitamin K Antagonists – Current Concepts and Challenges. Thrombosis Research 128:3, 210-215
CrossRef55
David Feinbloom, John Fani Srour. 2011. Heparin-Induced Thrombocytopenia. , 331-359.
CrossRef56
Taki Galanis, Geno J. Merli. 2011. Newer Oral Anticoagulants. , 67-80.
CrossRef57
J. Steffel, E. Braunwald. (2011) Novel oral anticoagulants: focus on stroke prevention and treatment of venous thrombo-embolism. European Heart Journal 32:16, 1968-1976
CrossRef58
TREVOR BAGLIN. (2011) Using the laboratory to predict recurrent venous thrombosis. International Journal of Laboratory Hematology 33:4, 333-342
CrossRef59
A. John Camm, Henri Bounameaux. (2011) Edoxaban. Drugs 71:12, 1503-1526
CrossRef60
M. M. Samama, G. Gerotziafas. (2011) Trois nouveaux anticoagulants disponibles en 2011: Dabigatran Etexilate, Rivaroxaban et Apixaban. Bio tribune magazine 38:1, 10-15
CrossRef61
E.M. Godfrey, A.L. Godfrey, D.J. Perry, A.S. Shaw. (2011) Don't be a clot: A radiologist's guide to haemostasis including novel antiplatelet and anticoagulant therapies. Clinical Radiology 66:8, 693-700
CrossRef62
Tripodi, Armando, Mannucci, Pier Mannuccio, . (2011) The Coagulopathy of Chronic Liver Disease. New England Journal of Medicine 365:2, 147-156
Full Text63
Masaki Watanabe, Fazeel M. Siddiqui, Adnan I. Qureshi. (2011) Incidence and Management of Ischemic Stroke and Intracerebral Hemorrhage in Patients on Dabigatran Etexilate Treatment. Neurocritical Care
CrossRef64
Carsten Perka. (2011) From proof to practice: innovations in total hip and total knee replacement—modern anticoagulation. European Orthopaedics and Traumatology 2:1-2, 3-5
CrossRef65
K. A. BAUER. (2011) Recent progress in anticoagulant therapy: oral direct inhibitors of thrombin and factor Xa. Journal of Thrombosis and Haemostasis 9, 12-19
CrossRef66
Drahomir Aujesky, Pierre-Marie Roy, Franck Verschuren, Marc Righini, Joseph Osterwalder, Michael Egloff, Bertrand Renaud, Peter Verhamme, Roslyn A Stone, Catherine Legall, Olivier Sanchez, Nathan A Pugh, Alfred N'gako, Jacques Cornuz, Olivier Hugli, Hans-Jürg Beer, Arnaud Perrier, Michael J Fine, Donald M Yealy. (2011) Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. The Lancet 378:9785, 41-48
CrossRef67
Thomas G. DeLoughery. (2011) Practical aspects of the oral new anticoagulants. American Journal of Hematology 86:7, 586-590
CrossRef68
Maryam Sattari, David T Lowenthal. (2011) Novel Oral Anticoagulants in Development: Dabigatran, Rivaroxaban, and Apixaban. American Journal of Therapeutics 18:4, 332-338
CrossRef69
J. VAN ES, E. S. EERENBERG, P. W. KAMPHUISEN, H. R. BÜLLER. (2011) How to prevent, treat, and overcome current clinical challenges of VTE. Journal of Thrombosis and Haemostasis 9, 265-274
CrossRef70
Alessandro Squizzato, Elena Rancan, Francesco Dentali. (2011) Pharmacotherapy of deep-venous thrombosis: current status and future perspective. Clinical Investigation 1:7, 1039-1047
CrossRef71
Elie A Akl, Nawman Labedi, Maddalena Barba, Irene Terrenato, Francesca Sperati, Paola Muti, Holger Schünemann, Elie A Akl. 2011. Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. .
CrossRef72
Francisco Buitrago Ramírez, José Antonio Morales Gabardino, Javier Alejandre Carmona. (2011) Tratamiento y prevención secundaria del tromboembolismo. FMC - Formación Médica Continuada en Atención Primaria 18:6, 366-378
CrossRef73
Luca Masotti, Mario Di Napoli, Daniel A. Godoy, Daniela Rafanelli, Giancarlo Liumbruno, Nicholas Koumpouros, Giancarlo Landini, Alessandro Pampana, Roberto Cappelli, Daniela Poli, Domenico Prisco. (2011) The practical management of intracerebral hemorrhage associated with oral anticoagulant therapy. International Journal of Stroke 6:3, 228-240
CrossRef74
Subroto Acharjee, Christopher P. Cannon. (2011) Dabigatran. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 10:2, 84-86
CrossRef75
Meyer Michel Samama. (2011) The mechanism of action of rivaroxaban – an oral, direct Factor Xa inhibitor – compared with other anticoagulants. Thrombosis Research 127:6, 497-504
CrossRef76
Sam Schulman, Ammar Majeed. (2011) A Benefit-Risk Assessment of Dabigatran in the Prevention of Venous Thromboembolism in Orthopaedic Surgery. Drug Safety 34:6, 449-463
CrossRef77
Tarek AN Ahmed, Ioannis Karalis, J Wouter Jukema. (2011) Emerging drugs for coronary artery disease. From past achievements and current needs to clinical promises. Expert Opinion on Emerging Drugs 16:2, 203-233
CrossRef78
Mátyás Keltai, Katalin Keltai. (2011) Új antikoagulánsok a vénás thromboembolia megelőzésében és kezelésében. Orvosi Hetilap 152:25, 983-992
CrossRef79
Stephen H. McKellar, Stuart Abel, Christopher L. Camp, Rakesh M. Suri, Mark H. Ereth, Hartzell V. Schaff. (2011) Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves. The Journal of Thoracic and Cardiovascular Surgery 141:6, 1410-1416
CrossRef80
Schwartz, Robert S., , Borissoff, Julian Ilcheff, Spronk, Henri M.H., ten Cate, Hugo, . (2011) The Hemostatic System as a Modulator of Atherosclerosis. New England Journal of Medicine 364:18, 1746-1760
Full Text81
Bénédicte Dumont, Dorothée Faille, Nadine Ajzenberg. (2011) Les nouveaux anticoagulants oraux. médecine/sciences 27:5, 493-500
CrossRef82
Arlene Tran, Angela Cheng-Lai. (2011) Dabigatran Etexilate. Cardiology in Review 19:3, 154-161
CrossRef83
Nadia Rosencher, Paul Zufferey, Silvy Laporte, Patrick Mismetti. (2011) Key features of the EXPANSE clinical program for apixaban in the prevention and treatment of thrombotic disorders. Clinical Investigation 1:5, 725-737
CrossRef84
J.M. Calvo Romero, E.M. Lima Rodríguez. (2011) Indicaciones del dabigatrán. SEMERGEN - Medicina de Familia 37:5, 252-254
CrossRef85
Andrea Piccioli, Paolo Prandoni. (2011) Approach to Venous Thromboembolism in the Cancer Patient. Current Treatment Options in Cardiovascular Medicine 13:2, 159-168
CrossRef86
Taki Galanis, Lynda Thomson, Michael Palladino, Geno J. Merli. (2011) New oral anticoagulants. Journal of Thrombosis and Thrombolysis 31:3, 310-320
CrossRef87
Marco P. Donadini, Walter Ageno. (2011) Which patients with unprovoked VTE should receive extended anticoagulation? the minority. Journal of Thrombosis and Thrombolysis 31:3, 301-305
CrossRef88
Clive Kearon. (2011) Extended anticoagulation for unprovoked venous thromboembolism: a majority of patients should be treated. Journal of Thrombosis and Thrombolysis 31:3, 295-300
CrossRef89
Henry Christensen, Jens-Jacob Lauterlein, Patricia D. Sørensen, Eva R.B. Petersen, Jonna S. Madsen, Ivan Brandslund. (2011) Home Management of Oral Anticoagulation via Telemedicine Versus Conventional Hospital-Based Treatment. Telemedicine and e-Health 17:3, 169-176
CrossRef90
K. P. CABRAL, J. ANSELL, E. M. HYLEK. (2011) Future directions of stroke prevention in atrial fibrillation: the potential impact of novel anticoagulants and stroke risk stratification. Journal of Thrombosis and Haemostasis 9:3, 441-449
CrossRef91
Pier Mannuccio Mannucci, Massimo Franchini. (2011) Old and new anticoagulant drugs: A minireview. Annals of Medicine 43:2, 116-123
CrossRef92
Kessarin Panichpisal, Michael Szarek, Amarjeet Sareen. (2011) Dabigatran for stroke prevention in patients with atrial fibrillation and previous stroke or transient ischemic attack: does dose matter?. Future Neurology 6:2, 155-158
CrossRef93
Gentian Denas, Vittorio Pengo. (2011) Emerging anticoagulants. Expert Opinion on Emerging Drugs 16:1, 31-44
CrossRef94
J.M. Calvo Romero. (2011) ¿Dabigatrán o antagonistas de la vitamina K en la prevención de ictus en pacientes con fibrilación auricular?. Revista Clínica Española 211:3, 142-146
CrossRef95
B. Planquette, G. Meyer. (2011) Embolie pulmonaire aiguë : prise en charge actuelle et perspectives. Revue des Maladies Respiratoires Actualités 3, S56-S60
CrossRef96
Dennis J. Cada, Terri L. Levien, Danial E. Baker. (2011) Formulary Drug Reviews - Dabigatran. Hospital Pharmacy 46:3, 196-204
CrossRef97
Bengt I. Eriksson, Daniel J. Quinlan, John W. Eikelboom. (2011) Novel Oral Factor Xa and Thrombin Inhibitors in the Management of Thromboembolism. Annual Review of Medicine 62:1, 41-57
CrossRef98
Susanne Lison, Michael Spannagl. (2011) Monitoring of direct anticoagulants. Wiener Medizinische Wochenschrift 161:3-4, 58-62
CrossRef99
Sorrel E Wolowacz. (2011) Pharmacoeconomics of dabigatran etexilate for prevention of thromboembolism after joint replacement surgery. Expert Review of Pharmacoeconomics & Outcomes Research 11:1, 9-25
CrossRef100
Charles Marc Samama. (2011) New anticoagulants: pharmacology and clinical studies. Wiener Medizinische Wochenschrift 161:3-4, 54-57
CrossRef101
Yang-Ki Kim. (2011) Clinical Year in Review of Venous Thromboembolism. Tuberculosis and Respiratory Diseases 71:4, 245
CrossRef102
M. Levi, E. S. Eerenberg, P. W. Kampuisen. (2011) Anticoagulants. Hämostaseologie 31:4, 229-235
CrossRef103
Amer Zeidan, Bishoy Faltas, Michael Streiff. (2011) Dabigatran etexilate: What do hospitalists need to know?. Journal of Hospital Medicinen/a-n/a
CrossRef104
Stephanie Young, Lisa Bishop, Laurie Twells, Carla Dillon, John Hawboldt, Patrick O'Shea. (2011) Comparison of pharmacist managed anticoagulation with usual medical care in a family medicine clinic. BMC Family Practice 12:1, 88
CrossRef105
Elisabeth Perzborn, Susanne Roehrig, Alexander Straub, Dagmar Kubitza, Frank Misselwitz. (2011) The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor. Nature Reviews Drug Discovery 10:1, 61-75
CrossRef106
Selvakumar Velu, Gregory YH Lip. (2011) Recent Progress in Antithrombotic Therapy for Atrial Fibrillation. Journal of Atherosclerosis and Thrombosis 18:4, 257-273
CrossRef107
Norikazu Yamada, Mashio Nakamura, Masaaki Ito. (2011) Current Status and Trends in the Treatment of Acute Pulmonary Thromboembolism. Circulation Journal 75:12, 2731-2738
CrossRef108
Jeffrey I. Weitz. (2011) Factor Xa and thrombin as targets for new oral anticoagulants. Thrombosis Research 127, S5-S12
CrossRef109
G. Palareti. (2011) Bleeding with anticoagulant treatments. Hämostaseologie 31:4, 237-242
CrossRef110
B. I. Eriksson, O. E. Dahl, M. H. Huo, A. A. Kurth, S. Hantel, K. Hermansson, J. M. Schnee, R. J. Friedman, . (2011) Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). Thrombosis and Haemostasis 105:4, 721-729
CrossRef111
Santiago Redondo, Maria-Paz Martinez, Marta Ramajo, Jorge Navarro-Dorado, Abelardo Barez, Teresa Tejerina. (2011) Pharmacological basis and clinical evidence of dabigatran therapy.. Journal of Hematology & Oncology 4:1, 53
CrossRef112
2011. Complications and Adverse Sequelae of Sclerotherapy. , 180-237.
CrossRef113
The EINSTEIN Investigators. (2010) Oral Rivaroxaban for Symptomatic Venous Thromboembolism. New England Journal of Medicine 363:26, 2499-2510
Full Text114
J. Cucurull i Canosa, S. Vega-Molpeceres, M. Just Sarobe, M. Escoda García. (2010) Exantema por dabigatrán. Revista Clínica Española 210:11, 590-591
CrossRef115
J. Ansell. (2010) Warfarin Versus New Agents: Interpreting the Data. Hematology 2010:1, 221-228
CrossRef116
H. Völler, S. Alban, D. Westermann. (2010) Neue orale Antikoagulanzien. Der Internist 51:12, 1571-1581
CrossRef117
A. Y. Y. Lee. (2010) Thrombosis in Cancer: An Update on Prevention, Treatment, and Survival Benefits of Anticoagulants. Hematology 2010:1, 144-149
CrossRef118
Julie A. Gayle, Alan D. Kaye, Adam M. Kaye, Rinoo Shah. (2010) Anticoagulants: Newer Ones, Mechanisms, and Perioperative Updates. Anesthesiology Clinics 28:4, 667-679
CrossRef119
Timothy A. Morris. (2010) New Synthetic Antithrombotic Agents for Venous Thromboembolism: Pentasaccharides, Direct Thrombin Inhibitors, Direct Xa Inhibitors. Clinics in Chest Medicine 31:4, 707-718
CrossRef120
Stephan H. Schirmer, Magnus Baumhäkel, Hans-Ruprecht Neuberger, Stefan H. Hohnloser, Isabelle C. van Gelder, Gregory Y.H. Lip, Michael Böhm. (2010) Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation. Journal of the American College of Cardiology 56:25, 2067-2076
CrossRef121
J. Harenberg, R. Bauersachs, C. Diehm, H. Lawall, H. Burkhardt, H. Gerlach, H. Darius, H. Völler, E. Rabe, M. Wehling. (2010) Antikoagulation im Alter. Der Internist 51:11, 1446-1455
CrossRef122
Josien van Es, Renée A. Douma, Victor E. A. Gerdes, Pieter W. Kamphuisen, Harry R. Büller. (2010) Acute pulmonary embolism. Part 2: treatment. Nature Reviews Cardiology 7:11, 613-622
CrossRef123
Kathleen A Hazlewood, Christy M Weiland. (2010) Advances in oral anticoagulants: focus on dabigatran etexilate. Expert Review of Clinical Pharmacology 3:6, 727-737
CrossRef124
A. J. ROSE, E. M. HYLEK, A. OZONOFF, A. S. ASH, J. I. REISMAN, D. R. BERLOWITZ. (2010) Patient characteristics associated with oral anticoagulation control: results of the Veterans AffaiRs Study to Improve Anticoagulation (VARIA). Journal of Thrombosis and Haemostasis 8:10, 2182-2191
CrossRef125
Massimo Franchini, Pier Mannuccio Mannucci. (2010) New anticoagulants in internal medicine: An update. European Journal of Internal Medicine 21:5, 466-467
CrossRef126
S. SCHULMAN, D. R. ANDERSON, T. J. BUNGARD, T. JAEGER, S. R. KAHN, P. WELLS, S. J. WILSON. (2010) Direct and indirect costs of management of long-term warfarin therapy in Canada. Journal of Thrombosis and Haemostasis 8:10, 2192-2200
CrossRef127
Paolo Prandoni. (2010) The treatment of venous thromboembolism in patients with cancer. Internal and Emergency Medicine 5:S1, 27-30
CrossRef128
Guillermo Ruiz-Irastorza, Mark Crowther, Ware Branch, Munther A Khamashta. (2010) Antiphospholipid syndrome. The Lancet 376:9751, 1498-1509
CrossRef129
Carlos Escobar, Vivencio Barrios, David Jimenez. (2010) REVIEW: Atrial Fibrillation and Dabigatran: Has the Time Come To Use New Anticoagulants?. Cardiovascular Therapeutics 28:5, 295-301
CrossRef130
R.J. Friedman, O.E. Dahl, N. Rosencher, J.A. Caprini, A.A. Kurth, C.W. Francis, A. Clemens, S. Hantel, J.M. Schnee, B.I. Eriksson. (2010) Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: A pooled analysis of three trials. Thrombosis Research 126:3, 175-182
CrossRef131
H. Bounameaux. (2010) Contemporary management of pulmonary embolism: the answers to ten questions. Journal of Internal Medicine 268:3, 218-231
CrossRef132
Jeremy S. Paikin, John W. Eikelboom, John A. Cairns, Jack Hirsh. (2010) New antithrombotic agents—insights from clinical trials. Nature Reviews Cardiology 7:9, 498-509
CrossRef133
Alessandro Parolari, L. Henry Edmunds. (2010) Invited Commentary. The Annals of Thoracic Surgery 90:3, 768
CrossRef134
Suresh Vedantham. (2010) Catheter-directed thrombolysis for deep vein thrombosis. Current Opinion in Hematology 17:5, 464-468
CrossRef135
Karen M Hook, Charles S Abrams. (2010) Treatment options in heparin-induced thrombocytopenia. Current Opinion in Hematology 17:5, 424-431
CrossRef136
S. Schulman. (2010) New aspects on treatment modalities for thromboembolic episodes. Journal of Internal Medicine 268:2, 109-119
CrossRef137
Catherine J. Lee, Gauri Badhwar, Jack E. Ansell. (2010) Oral IIa Inhibitors. Hematology/Oncology Clinics of North America 24:4, 739-753
CrossRef138
R. G. Davies, R. Rayment. (2010) Primum non nocere - NICE guidelines on venous thromboembolism. Anaesthesia 65:8, 774-778
CrossRef139
Daniel M. Witt. (2010) Optimizing Use of Current Anticoagulants. Hematology/Oncology Clinics of North America 24:4, 717-726
CrossRef140
Agnelli, Giancarlo, Becattini, Cecilia, . (2010) Acute Pulmonary Embolism. New England Journal of Medicine 363:3, 266-274
Full Text141
Adam Torbicki. (2010) Enfermedad tromboembólica pulmonar. Manejo clínico de la enfermedad aguda y crónica. Revista Española de Cardiología 63:7, 832-849
CrossRef142
Eline A. Dubois, Adam F. Cohen. (2010) Dabigatran etexilate. British Journal of Clinical Pharmacology 70:1, 14-15
CrossRef143
O. Lomas, R. A. Argyle, B. D. Prendergast. (2010) Will direct thrombin inhibition change the boundaries of oral anti-coagulation?. QJM 103:6, 429-434
CrossRef144
Benjamin J. Wrigley, Gregory Y. H. Lip, Eduard Shantsila. (2010) Novel oral anticoagulants: the potential relegation of vitamin K antagonists in clinical practice. International Journal of Clinical Practice 64:7, 835-838
CrossRef145
(2010) Scientific Surgery. British Journal of Surgery 97:6, 964-964
CrossRef146
Rohtesh S Mehta. (2010) Novel oral anticoagulants. Part II: direct thrombin inhibitors. Expert Review of Hematology 3:3, 351-361
CrossRef147
Kanjaksha Ghosh, Kinjalka Ghosh. (2010) Advances in Haematological Pharmacotherapy in 21st Century. Indian Journal of Hematology and Blood Transfusion 26:2, 30-40
CrossRef148
Ola E Dahl, Menno V Huisman. (2010) Dabigatran etexilate: advances in anticoagulation therapy. Expert Review of Cardiovascular Therapy 8:6, 771-774
CrossRef149
Agnes Y.Y. Lee. (2010) The roles of anticoagulants in patients with cancer. Thrombosis Research 125, S8-S11
CrossRef150
Michael B. Streiff. (2010) The National Comprehensive Cancer Center Network (NCCN) guidelines on the management of venous thromboembolism in cancer patients. Thrombosis Research 125, S128-S133
CrossRef151
Lori-Ann Linkins, Jeffrey I. Weitz. (2010) New and Emerging Anticoagulant Therapies for Venous Thromboembolism. Current Treatment Options in Cardiovascular Medicine 12:2, 142-155
CrossRef152
Jeffrey I. Weitz. (2010) Potential of new anticoagulants in patients with cancer. Thrombosis Research 125, S30-S35
CrossRef153
H. BOUNAMEAUX, G. REBER. (2010) New oral antithrombotics: a need for laboratory monitoring. Against. Journal of Thrombosis and Haemostasis 8:4, 627-630
CrossRef154
(2010) Dabigatran versus Warfarin for Venous Thromboembolism. New England Journal of Medicine 362:11, 1050-1051
Full Text155
Walter Ageno. (2010) Recent advances in the management of venous thromboembolism. The Korean Journal of Hematology 45:1, 8
CrossRef156
Rajiv K. Pruthi. (2010) ASH 2009 meeting report-Top 10 clinically oriented abstracts in coagulation medicine and platelet disorders. American Journal of HematologyNA-NA
CrossRef157
A. Sautet. 2010. La prévention thrombo-embolique en chirurgie orthopédique et traumatologique majeure. , 269-278.
CrossRef
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