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New Therapy Update

Dabigatran Etexilate: The First Oral Anticoagulant Available in the United States Since Warfarin

Tran, Arlene PharmD; Cheng-Lai, Angela PharmD, BCPS

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doi: 10.1097/CRD.0b013e3182137758
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Of the anticoagulants available, many agents, such as heparin, low molecular weight heparins (LMWH), and the indirect-acting factor Xa inhibitor fondaparinux, must be given parenterally, and therefore may not be ideal for the chronic management of thromboembolism. Warfarin, however, can be given orally and is more suitable for chronic use. In fact, warfarin has been used almost exclusively in the past 50 years when oral anticoagulation is required. Warfarin has been shown to be effective in the prevention as well as treatment of various thromboembolic disorders. In addition, warfarin has an advantage of a long half-life which allows for once daily dosing. In spite of this, warfarin has a number of shortcomings which make this agent undesirable to use at times. Major drawbacks of warfarin include increased risk for bleeding, slow onset of therapeutic effect, difficulty in achieving optimal anticoagulation, unpredictable and significant interindividual variability in pharmacological response, a narrow therapeutic window which necessitates frequent international normalized ratio (INR) monitoring, and a number of drug-drug and drug-food interactions that could lead to subtherapeutic effect or increased risk for bleeding.1 Due to these limitations, the search of a new oral anticoagulant was warranted.

In recent years, direct thrombin inhibitors have been studied extensively and held promise in the treatment and prevention of various thromboembolic disorders. Most direct thrombin inhibitors (argatroban, bivalirudin, and lepirudin) must be given parenterally and are used primarily in the treatment of heparin-induced thrombocytopenia and in patients undergoing percutaneous coronary interventions. Desirudin also requires parenteral administration, and it is indicated for deep venous thrombosis prophylaxis in patients undergoing elective hip replacement surgery. Ximelagatran, the first oral direct thrombin inhibitor, has shown comparable efficacy to warfarin for the prophylaxis of venous thromboembolism as well as for stroke prevention in atrial fibrillation.2 Unfortunately, ximelagatran was not approved in the United States due to the concerns for hepatotoxicity and a higher rate of coronary artery disease events observed in long-term studies.3

Dabigatran etexilate (Pradaxa, Boehringer Ingelheim) is a new oral direct thrombin inhibitor and the first one of its kind to be available in the United States. Unlike ximelagatran, dabigatran does not appear to cause liver toxicity. Because dabigatran etexilate has shown a predictable anticoagulation response, it does not require routine anticoagulation monitoring which can be seen as a major advantage over warfarin. It also has a fast onset and offset of action, thereby negating the need for initial anticoagulation given by the parenteral route. Furthermore, dabigatran is not affected by changes in diet and has less drug-drug interactions compared with warfarin. In October 2010, dabigatran etexilate received US Food & Drug Administration approval for risk reduction in stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Although dabigatran etexilate has also demonstrated efficacy in the primary and secondary prevention of venous thromboembolism, these therapeutic uses are currently not approved in the United States. This article will provide a focused review on the pharmacokinetic and pharmacodynamic profiles of dabigatran etexilate as well as discuss its safety, clinical efficacy, and other therapeutic considerations for the use of this agent.


Thrombin, a plasma serine protease, plays an integral role in the formation of a clot. It is responsible for the conversion of fibrinogen to fibrin as well as clotting factor activation.3 Because platelet activation and aggregation is most physiologically stimulated by thrombin, the inhibition of thrombin is an ideal mode of action for an anticoagulant agent. Dabigatran is a direct thrombin inhibitor that inhibits both fibrin-bound and free thrombin in a competitive, selective, and reversible manner.4 Similar to argatroban, dabigatran binds only to the active site of thrombin to exert its antithrombin effects.3

Although coagulation monitoring generally is not required with dabigatran therapy, the correlation of dabigatran plasma concentration and several coagulation parameters have been examined. Among these parameters, thrombin time and ecarin clotting time appear to best reflect the effects of changing dabigatran concentrations. However, each method has its own shortcomings. Thrombin time measurements are dependent on the reagent used. These reagents are not widely standardized which may make interpretation difficult. Further, in cases of overdose, measuring thrombin time may be of limited value because many coagulometers are unable to measure a thrombin time for a dabigatran concentration over 600 ng/mL (a steady state concentration of 199 ng/mL may be reached after multiple doses of dabigatran 200 mg).5 Unlike thrombin time, ecarin clotting time is not available for routine use and is more frequently used in research.6 Other less sensitive parameters, such as activated partial thromboplastin time, may be alternate assays when dabigatran monitoring is necessary. In contrast, INR monitoring is not recommended due to the lack of a strong correlation with dabigatran concentrations.1

Dabigatran etexilate is a prodrug designed for oral administration and absorption in the gastrointestinal (GI) tract. Once absorbed, dabigatran etexilate is rapidly and almost completely hydrolyzed into 2 intermediate metabolites, BIBR 1087 and BIBR 951, by esterases found in the plasma and liver.4 These products are further metabolized to the final active agent, dabigatran.1 The cytochrome P450 system, a source of many drug interactions, is not involved in the processing of dabigatran etexilate or its metabolites.7

The bioavailability of dabigatran etexilate, the oral prodrug, ranges from 3% to 7%. It is recommended that the capsules should not be opened, crushed, or chewed because the bioavailability can be increased by up to 75%.8 The absorption of dabigatran etexilate depends on the presence of an acidic environment. Commercially available formulations of dabigatran etexilate contain tartaric acid. This allows for reliable, consistent absorption of the agent despite fluctuations in stomach pH. Studies looking at the effect of food intake on absorption have shown that food only prolongs the time to the peak blood concentration. Overall drug exposure and peak drug concentration were not affected by food.9 In general, the time to peak drug concentration occurs at approximately 1.5 to 3 hours after oral administration.4 The time to peak drug concentration parallels the maximal effect of dabigatran on coagulation (within 2 hours postingestion in healthy volunteers).

Dabigatran has a volume of distribution of 50 to 70 liters, suggesting that some drug distributes into the tissue because it is greater than the volume of total body water. As dabigatran is approximately 35% protein bound, interactions involving protein binding are not thought to be clinically relevant.4,8 The time to steady state concentrations is approximately 3 days. Approximately 80% of the administered drug is excreted in the urine when dabigatran is administered intravenously. The remaining dabigatran undergoes conjugation and glucuronidation within the liver. These products, which retain activity, are then eliminated through the bile.4 Anticoagulant action seems to correlate with the elimination half-life because a decrease to half of the peak activity at 12 hours postadministration was observed. The elimination half-life is 12 to 17 hours after multiple doses in healthy patients with normal renal function.3,8 Based on pharmacokinetic models, the half-life is prolonged in patients with renal dysfunction. With mild and moderate renal dysfunction, the estimated half-lives are 15 and 18 hours, respectively.8


The decision to approve dabigatran for venous thromboembolic (VTE) prophylaxis in patients with atrial fibrillation in the United States is primarily based on 2 major studies—the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) and Prevention of Embolic and Thrombotic Events in Patients with Persistent Atrial Fibrillation (PETRO) trials. Studies exploring the use of dabigatran for VTE prophylaxis in patients with total hip and knee arthroplasty and for secondary prevention of VTE have been conducted but neither are approved indications in the United States. Major trials exploring the use of dabigatran in these 3 patient populations are reviewed later in the text and are summarized in Table 1.

Landmark Trials of Dabigatran

Trials Exploring Dabigatran for the Prevention of VTE in Patients With Atrial Fibrillation

RE-LY Trial

The RE-LY trial was a multinational, phase III, noninferiority study which randomized 18,113 patients to either 110 mg or 150 mg of dabigatran twice daily or open-label warfarin.9 Patients were included in the study if there was a diagnosis of atrial fibrillation and an increased risk for stroke. An increased risk of stroke was defined as having a previous stroke or transient ischemic attack, a left ventricular ejection fraction of <40%, New York Heart Association (NYHA) class II or higher heart failure symptoms within 6 months, an age of ≥75, or an age of 65 to 74 with diabetes mellitus, hypertension, or coronary artery disease. The primary efficacy and safety outcomes compared were the incidences of stroke or systemic embolism and major hemorrhage, respectively, over a median of 2 years. These outcomes were measured through follow-up visits, patient chart reviews, and symptom questionnaires. Baseline characteristics were similar among all treatment groups. The incidence of stroke or systemic embolism was 1.53% per year for patients on dabigatran 110 mg twice daily (relative risk [RR], 0.91; confidence interval [CI], 0.74–1.11; P < 0.001 for noninferiority), 1.11% per year for patients on 150 mg twice daily (RR, 0.66; 95% CI, 0.53–0.82; P < 0.001 for noninferiority and superiority), and 1.69% per year for patients on warfarin. Major bleeding occurred at a rate of 2.71% per year in the dabigatran 110 mg twice daily group (RR, 0.80; 95% CI, 0.69–0.93; P = 0.003), 3.11% per year for patients on dabigatran 150 mg twice daily (RR, 0.93; 95% CI, 0.81–1.07; P = 0.31), and 3.36% per year in the warfarin group.

Although the primary end points suggest that the efficacy and safety of dabigatran are noninferior to warfarin, some secondary end points should be highlighted. For example, a slightly higher incidence of myocardial infarctions in patients who receive dabigatran compared with warfarin was noted. The authors suggest that this finding may be due to possible myocardial protective effects of warfarin not yet elucidated. A higher incidence of GI bleeding was also noted in patients who received dabigatran 150 mg twice daily as compared with warfarin (RR, 1.50; 95% CI, 1.19–1.89; P < 0.001). Overall, dabigatran 110 mg twice daily was found to be noninferior, and dabigatran 150 mg twice daily superior, to warfarin in the prevention of stroke and systemic embolism. The lower dose of dabigatran was observed to have a lower risk of major bleeds, while dabigatran 150 mg twice daily was found to have no difference in frequency when compared with warfarin.9 More recently, further analysis of the RE-LY trial demonstrated that dabigatran was similar to warfarin at 30 days after cardioversion for atrial fibrillation, with a low frequency of stroke and major bleeding.10


The PETRO study was a multicenter, phase II trial.11 The goal of PETRO was to determine the safety of dabigatran doses in patients with atrial fibrillation over 12 weeks. The inclusion criteria consisted of patients with atrial fibrillation with one or more of the following: hypertension requiring medical therapy, diabetes mellitus, symptomatic heart failure or an left ventricular ejection fraction <40%, age >75 years, a previous stroke, or a prior transient ischemic attack. A total of 502 patients were randomized to dabigatran or warfarin groups. Those patients randomized to dabigatran received the medication at 50, 150, or 300 mg twice daily along with no aspirin, aspirin 81 mg or 325 mg once daily in a 3 × 3 factorial manner. The dose of dabigatran was double-blinded but open-label for concurrent aspirin use. Warfarin was administered in an open-label manner. The primary outcome studied was the frequency of bleeding events that comprised of both major and minor bleeding episodes. Monitoring was completed on an outpatient basis throughout the 12 weeks.

Baseline characteristics were noted to be similar among all treatment groups (P > 0.1). The overall incidence of bleeding was greatest in patients who received dabigatran 300 mg twice daily with aspirin 81 or 325 mg daily. Of the 34 patients who received dabigatran 300 mg twice daily with aspirin 81 mg daily, 11 patients experienced bleeding. Bleeding was noted in 14 of the 30 patients who were administered dabigatran 300 mg twice daily with aspirin 325 mg daily. The overall incidence of bleeding was least in patients who received dabigatran 50 mg twice daily, but there were also 2 thromboembolic events noted in these groups. A 17.1% incidence of bleeding was noted for warfarin, similar to the incidence seen with dabigatran 150 mg or 300 mg twice daily without aspirin. Because many patients with atrial fibrillation have comorbidities that require aspirin therapy, the authors concluded that the increased bleeding observed in the PETRO Trial in patients on dabigatran and aspirin should guide further studies. Insight into the dose-response bleeding effects and the upper limit of tolerability of dabigatran was also established.11

Of note, patients randomized to warfarin were within an INR range of 2 to 3 approximately 64% of the time in the RE-LY and PETRO trials.9,11 Although the percentage of time within therapeutic range is consistent with other studies, it is arguable that the warfarin therapy may not have been optimally managed.18 A trial with almost all patients being within target INR range, during most of the study period could potentially alter the study's conclusions. However, in practice, maintaining an ideal INR for most of patients is unrealistic. Given the above issues, it is unclear if the results of these trials and their clinical impact would stand in the setting of tightly controlled warfarin therapy.

Trials Exploring Dabigatran for Primary and Secondary Prevention of VTE

The incidence of VTE in patients undergoing total hip replacement was historically >50% without thromboprophylaxis.12 In patients with a high risk of bleeding, mechanical thromboprophylaxis is suggested. Otherwise, the use of LMWH, fondaparinux, or warfarin (titrated to an INR of 2.0–3.0) for the prevention of VTE in patients undergoing total knee and hip replacement is currently being recommended by the 2008 American College of Chest Physicians guideline.19 Dabigatran is approved for use in the prevention of VTE for patients undergoing total hip or knee replacement in Canada and Europe, but not in the United States.

Table 1 summarizes the major dabigatran trials in patients undergoing total hip or knee replacement. The aggregate of these studies suggests that dabigatran etexilate appears to be noninferior to the LMWHs, in particular, enoxaparin, in the prevention of VTE post total hip or knee replacement surgery.14,15 Dabigatran etexilate exhibited superiority in VTE prevention in these patients at higher doses in the BISTRO II study.13 RE-MOBILIZE was the only major trial where dabigatran was observed to be inferior to enoxaparin. The researchers speculated that this finding was due to enoxaparin being dosed at 30 mg twice daily instead of 40 mg once daily.16 In general, a dose-response trend was observed in these trials with patients receiving the lower dose of dabigatran experiencing an increased frequency of VTE. Bleeding rates also appear to be dose-related, with increasing bleeding events associated with increasing doses of dabigatran.12 Although considered similar to enoxaparin, the rates of bleeding in the total knee or hip replacement population were slightly more with higher doses of dabigatran.13 It should be noted that these dabigatran doses have only been tested in patients at least 18 years of age and >40 kg in weight. The dosing, efficacy, and safety remain unclear in patients who are <18 years of age and <40 kg in weight.

In addition to primary prevention of VTE, the secondary prevention of VTE with dabigatran has also been studied. The safety and efficacy of dabigatran for the prevention of recurrent VTE were explored in the RE-COVER trial.17 The RE-COVER trial was a randomized, double-blind, noninferiority study which compared dabigatran to warfarin in the prevention of recurrent VTE and associated deaths. The authors noted a VTE or VTE-related death incidence of 2.4% in patients receiving dabigatran and 2.1% in patients receiving warfarin. The calculated hazard ratio (HR) associated with this primary outcome incidence was 1.10 (95% CI, 0.65–1.84) for dabigatran. The incidence of overall bleeding was 16.1% in the dabigatran group and 21.9% in those who received warfarin (HR, 0.71; 95% CI, 0.59–0.85). Although these results showed promise for dabigatran in the secondary prevention of VTE, this agent is not currently approved for the prevention of recurrent VTE in patients who have experienced a deep vein thrombosis or pulmonary embolism.17

Overall, it appears that a dose-response relationship exists for both efficacy and safety. As doses are increased, decreases in the number of VTE episodes and increases in the rates of bleeding events occur. This effect seen with dabigatran is contrary to the findings of BISTRO I which may be explained by the smaller population of the patient in that trial. The use of aspirin also appears to increase the rates of bleeding when given in conjunction with dabigatran. As such, these effects may not be definitively attributed to dabigatran alone.


Dabigatran etexilate is indicated for the prevention of stroke and systemic embolization in patients with nonvalvular atrial fibrillation. It is available as 75 mg and 150 mg capsules. Dabigatran capsules may be taken without regard to food and are to be swallowed whole and not chewed, broken, or opened. In patients with a creatinine clearance (CrCl) >30 mL/min, dabigatran should be administered at 150 mg orally twice daily, while patients with a CrCl of 15 to 30 mL/min should be given 75 mg orally twice daily. Dosing recommendations are not available in patients with a lower CrCl or on hemodialysis.8

In patients who are being converted to dabigatran from warfarin, dabigatran should be initiated once warfarin has been discontinued and the INR is <2.0. Conversely, the transition from dabigatran to warfarin is dependent on the renal function of the patient. In patients with a CrCl >50 mL/min, warfarin should be initiated 3 days prior to discontinuing dabigatran. The initiation of warfarin 2 days before dabigatran discontinuation is recommended for patients with a CrCl of 31 to 50 mL/min. Warfarin should be started 1 day before the discontinuation of dabigatran in patients with a CrCl of 15 to 30 mL/min.8

When converting a patient from a parenteral anticoagulant to dabigatran, it is suggested that dabigatran etexilate be given 0 to 2 hours before the dose of the parenteral anticoagulant was to have been administered. Dabigatran should be given at the time of discontinuation of an anticoagulant that is given as a continuous infusion. In contrast, when switching from dabigatran to a parenteral anticoagulant, patients with a CrCl <30 mL/min should wait 24 hours between the last dose of dabigatran and the first dose of the parenteral anticoagulant. The parenteral anticoagulant should be administered 12 hours after the last dose of dabigatran in patients with a CrCl of ≥30 mL/min.8

Drug-free periods, or a period of time when drug is not taken, are recommended when a surgery or invasive procedure is planned. The length of time that the drug is held is based on the patient's renal function, the type of procedure, and the acuity of the situation. In patients with a CrCl ≥50 mL/min, the manufacturer has recommended that dabigatran be held 1 to 2 days prior to the scheduled procedure. A 3 to 5 day period of holding dabigatran is recommended when the patient's CrCl is <50 mL/min. With major surgeries or spinal/epidural procedures, longer drug-free periods may be considered but no specific recommendations have been provided by the manufacturer. A similar lack of manufacturer guidance exists in the acute setting where the risk for bleeding is weighed against the need for the procedure.8

As a new treatment option, the cost of therapy may dictate the ultimate choice between 2 equally efficacious options. The wholesale cost of dabigatran has been quoted as $6.75 for two 150 mg capsules or approximately $200 for a 30-day supply.20 The cost of dabigatran is staggering when compared with a 30-day supply of warfarin offered for $4 at several major retail chains. Abdelhafiz and Wheeldon21 examined the total annual cost of warfarin therapy with monitoring and found that this figure was an average of £159.4 in 2003 (approximately $250). The mean cost associated with warfarin monitoring alone was determined to be £90.4 per year (about $140). Another study exploring the costs of warfarin monitoring at 3 ambulatory care sites in the United States showed that the observed annual cost ranged between $200 and $300 in 2005.22 Although the convenience of not having to regularly obtain laboratory values and adjust doses is attractive, the drug cost of dabigatran therapy appears to be more than the cost of warfarin and INR monitoring combined. As of the writing of this review, the true difference in cost between dabigatran and warfarin use have yet to be determined.


Common side effects observed with dabigatran were GI in nature. GI symptoms were reported in 35% of patients who received dabigatran 150 mg as compared with the 24% of patients on warfarin.8 In the RE-LY trial, the incidences of dyspepsia were noted to be 5.8% in patients on warfarin, 11.8% of patients receiving dabigatran 110 mg twice daily, and 11.3% of patients on dabigatran 150 mg twice daily. Researchers have hypothesized that the dyspepsia is secondary to the tartaric acid, the inactive ingredient that guarantees an acidic pH suitable for the absorption of dabigatran.

As noted in the studies reviewed, the risk of overall bleeding appears to be similar to that of warfarin. However, in the RE-LY study, it was noted that the rate of major bleeding within the gastrointestinal tract was greater with dabigatran. The group of patients on dabigatran 150 mg twice daily had an incidence of 1.51% per year for major bleeding of the gastrointestinal tract. This is compared with the 1.02% per year of patients who experienced a major GI bleed while on warfarin. In the same trial, it was also observed that patients on warfarin experienced a significantly higher incidence of intracranial hemorrhages as compared with dabigatran.9 It should be noted that most trials were only powered to determine if a difference in the incidence of overall bleeding existed between dabigatran and the other agents.

Unlike ximelagatran, dabigatran does not appear to have any hepatotoxic effects. The RE-LY trial found that the incidence of increases in liver function tests to >3 times the upper limit of normal was no more frequent than the observed rate in patients on warfarin.9 Studies have also shown that the rates of transient liver function test elevations were similar to enoxaparin. The incidence of alanine aminotransferase increases to >3 times the upper limit of normal occurred in 3% of patients who received dabigatran 150 mg per day, 3% of those who received dabigtran 220 mg per day, and 5% in patients who received enoxaparin 40 mg per day.7


Several potential drug interactions were observed in clinical trials with dabigatran. For example, dabigatran is a substrate of P-glycoprotein, an efflux pump. Quinidine, a potent P-glycoprotein inhibitor, was found to increase the peak concentration of dabigatran by 56% and total drug exposure by 53%. The concurrent use of quinidine with dabigatran eventually became part of the exclusion criteria in the RE-LY trial. Other P-glycoprotein inhibitors shown to increase the peak dabigatran concentration are ketoconazole, amiodarone, and verapamil. Despite these effects, the manufacturer has recommended that changes in dosing are not required while using these specific inhibitors. It is unknown whether dosage adjustments are needed for other P-glycoprotein inhibitors. Unlike the P-glycoprotein inhibitors, inducers of this pump decreased the concentration of dabigatran. Rifampin, an inducer was observed to decrease the peak concentration of dabigatran by 67% and the total drug exposure by 66%. These effects lasted for approximately 7 days after stopping rifampin use. Avoidance of P-glycoprotein inducers is recommended by the manufacturer while on dabigatran.8

As discussed earlier, the absorption of dabigatran etexilate requires an acidic environment. Medications that can alter the pH of the GI environment, like proton pump inhibitors, may also alter the maximum plasma concentration of dabigatran. A study evaluating the use of pantoprazole and dabigatran has shown that peak plasma concentration and the area under the curve of dabigatran were decreased when both agents were taken together (33% and 22%, respectively). The authors concluded that these decreases were not clinically significant and the manufacturer has not recommended any changes in dosing.8,23


Dabigatran is a new oral direct thrombin inhibitor shown to be noninferior to warfarin in the prevention of stroke and systemic embolism in the setting of atrial fibrillation. Unlike other anticoagulants, dosage adjustments based on measurements of clotting parameters are not regularly required, adding to the convenience of dabigatran. The lack of many drug-drug and drug-food interactions observed also differentiates dabigatran from warfarin. The noninferiority of dabigatran as compared with warfarin in terms of safety and efficacy, in addition to the aforementioned benefits, allow dabigatran to be a viable and attractive option for anticoagulation in the outpatient setting.

Despite these advantages, the use of dabigatran is not without adverse events and shortcomings. Patients should be counseled on dyspepsia, one of the more common adverse events, prior to being placed on dabigatran. It appears that the higher discontinuation rates observed in the dabigatran group of the RE-LY trial may be a consequence of GI intolerance. A higher incidence of myocardial infarction was also observed in patients who received dabigatran in the RE-LY trial. It is not known if this observation is due to the possible protective effects of warfarin or to the possible platelet activating effects of dabigatran. Further postmarketing experience with dabigatran use should help to address this issue. A substudy is currently ongoing to evaluate the platelet effects of dabigatran.

Unlike warfarin, there is no antidote for the anticoagulant effect of dabigatran. The lack of reversibility of dabigatran anticoagulant effect can be a concern during acute bleeding. Because the absorption of dabigatran etexilate depends on an acidic environment which is provided by the tartaric acid in the commercially available formulation, the capsules must be swallowed whole and cannot be broken and administered down a feeding tube. The inability to break dabigatran capsules can be especially problematic for patients who cannot swallow medications. Another population that cannot use dabigatran are those with severe renal impairment (CrCl <15 mL/min and patients on dialysis) since dosing guidelines in these patients are not available.

Just as it is an advantage for patients on dabigatran to omit regular coagulation monitoring, the elimination of routine monitoring can also be a disadvantage. The reduction of visits with healthcare providers may lead to missed opportunities for quality patient care and interventions. Furthermore, the assessment of therapy compliance via INR monitoring could be lost with dabigatran. Enforcement of compliance may also be more difficult to achieve since dabigatran is dosed twice daily instead of once daily.


With all things considered, dabigatran remains a promising alternative to warfarin. The aforementioned advantages and disadvantages may help to distinguish individuals who would benefit most from this drug. The role of dabigatran as an anticoagulant may be better defined as more data become available. Studies examining the long-term efficacy and safety of dabigatran in patients with atrial fibrillation are currently ongoing.24 Other trials continue to explore dabigatran use in knee and hip replacement surgeries, in children, and in patients with renal dysfunction. Data provided from these trials may further define the role of dabigatran in patients with atrial fibrillation, its dosing in special populations, its cost effectiveness, and may even lead to new indications.


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dabigatran etexilate; oral anticoagulant; direct thrombin inhibitor

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