Dabigatran Etexilate: A Review in Nonvalvular Atrial Fibrillation

Drugs ◽  
2017 ◽  
Vol 77 (3) ◽  
pp. 331-344 ◽  
Author(s):  
Hannah A. Blair ◽  
Gillian M. Keating
Author(s):  
Eileen Fonseca ◽  
David R Walker ◽  
Gregory P Hess

Background: Warfarin and dabigatran etexilate (DE) are oral anticoagulants (OAC) used to reduce the risk of stroke among patients with nonvalvular atrial fibrillation (AF). However, DE does not require titration and INR monitoring. This study examined whether hospital length of stay (LOS) and total hospital costs differed between the two therapies among treatment-naive, newly-diagnosed AF patients. Methods: LOS and total hospital costs were evaluated for hospitalizations with a primary or secondary discharge diagnosis of atrial fibrillation (AF) between 1/1/2011-3/31/2012, with DE or warfarin administered during hospitalization, and excluding hospitalizations of patients with valvular AF, previously diagnosed with AF, or previously treated with OAC. Hospitalizations were identified from a Charge Detail Masters database containing 397 qualified hospitals. Samples were propensity score matched using nearest neighbor within a caliper of 0.20 standard deviations of the logit, without replacement and a 2:1 match. Differences in LOS and hospital cost were then estimated using generalized linear models, fitted by generalized estimating equations (clustered by hospital) to account for possible correlation between observations. The hospitalization’s charged amount was multiplied by the hospital’s inpatient cost-to-charge ratio to estimate the total hospital cost. Covariates estimating the propensity score, LOS, and costs included patient age, payer type, CHADS 2 and HAS-BLED scores, use of bridging agents, comorbid conditions, and hospital attributes. As a sensitivity analysis, LOS and costs were estimated with the same parameters and covariates among the raw, unbalanced sample. Results: Matched samples included 1,292 warfarin and 646 DE hospitalizations of treatment-naive, newly diagnosed patients out of 4,619 and 715 hospitalizations, respectively. No covariates used in matching had standardized mean differences > 10% after matching. Two comorbidities (thromboembolism, coronary artery disease) had statistically different distributions after matching (DE: 3% vs. warfarin: 8%, p<0.001 and DE: 40% vs. warfarin: 45%, p=0.048); these were included as model covariates. Among the sample, DE had an estimated 0.7 days shorter stay compared to warfarin (DE: 4.8 days vs. warfarin: 5.5 days, p<0.01) and a $2,031 lower estimated total cost (DE: $14,794 vs warfarin: $16,826, p=0.007). Sensitivity analysis confirmed a shorter DE LOS (DE: 5.5 days vs. warfarin: 6.6 days, delta=1.1 days, p<0.01) and a lower DE hospital cost (DE: $18,362 vs. warfarin: $22,602, delta=$4,240, p<0.01). Conclusions: Among hospitalizations of treatment-naive patients newly diagnosed with nonvalvular AF, the hospitalizations during which DE was administered had a shorter LOS and at least a 12% lower total hospital cost compared to hospitalizations where warfarin was administered.


Author(s):  
Eileen Fonseca ◽  
David R Walker ◽  
Gregory P Hess

Background: Warfarin and dabigatran etexilate (DE) are oral anticoagulants (OAC) that reduce stroke risk among patients with nonvalvular atrial fibrillation (AF). However, DE does not require titration and INR monitoring. This study examined whether emergency department (ED) rate of admissions differed between the two therapies. Methods: Admission rate was evaluated for hospital encounters initiated in the ED, with a primary or secondary discharge diagnosis of AF between 1/1/2011-3/31/2012, with DE or warfarin administered during the encounter, and excluding encounters of valvular AF patients. Encounters were identified from a hospital Charge Detail Masters database containing 387 eligible hospitals. Samples were propensity score matched using nearest neighbor within a caliper of 0.20 standard deviations of the logit, without replacement, and a 2:1 match. Admission rates were estimated for encounters representing previously-treated patients and those representing treatment-naive patients using binominal generalized linear models, fitted by generalized estimating equations (clustered by hospital). Covariates estimating the propensity score and admission rate included age, payer type, use of bridging agents, AF as primary or secondary diagnosis, CHADS 2 and HAS-BLED scores, comorbid conditions, and hospital attributes. As a sensitivity analysis, admission rate was also estimated from the unmatched sample. Results: Matched samples included 2,688 warfarin and 1,344 DE ED encounters of previously-treated patients out of 15,053 and 1,367 ED encounters, respectively; and 2,578 warfarin and 1,289 DE ED encounters of OAC-treatment-naive patients out of 8,361 and 1,406 ED encounters, respectively. There were too few (n<5) matched encounters where the patient had prior OAC use but were new to the drug administered during the encounter, so these were excluded. No covariates used in matching had standardized mean differences > 10% after matching. Among the previously-treated sample, the estimated admission rate was 3.2% lower for DE compared to warfarin (88.3% vs. 91.5%, p=0.010) with sensitivity analysis confirming a lower admission rate for DE (91.1% vs. 93.8%, delta=2.7%, p=0.001). Among the treatment-naive sample, DE had a 1.2% lower admission rate compared to warfarin (95.2% vs. 96.3%, p=0.048). Sensitivity analysis confirmed a lower admission rate for DE (95.5% vs. 97.0%, delta=1.5%, p=0.001). Conclusions: While the vast majority of AF encounters initiated in the ED result in admission, encounters where patients were treated with DE as continuing or new therapy were less likely to be admitted compared to similar encounters where warfarin was administered.


2011 ◽  
Vol 2011 ◽  
pp. 1-23 ◽  
Author(s):  
M. Àngels Font ◽  
Jerzy Krupinski ◽  
Adrià Arboix

Embolism of cardiac origin accounts for about 20% of ischemic strokes. Nonvalvular atrial fibrillation is the most frequent cause of cardioembolic stroke. Approximately 1% of population is affected by atrial fibrillation, and its prevalence is growing with ageing in the modern world. Strokes due to cardioembolism are in general severe and prone to early recurrence and have a higher long-term risk of recurrence and mortality. Despite its enormous preventive potential, continuous oral anticoagulation is prescribed for less than half of patients with atrial fibrillation who have risk factors for cardioembolism and no contraindications for anticoagulation. Available evidence does not support routine immediate anticoagulation of acute cardioembolic stroke. Anticoagulation therapy's associated risk of hemorrhage and monitoring requirements have encouraged the investigation of alternative therapies for individuals with atrial fibrillation. New anticoagulants being tested for prevention of stroke are low-molecular-weight heparins (LMWH), unfractionated heparin, factor Xa inhibitors, or direct thrombin inhibitors like dabigatran etexilate and rivaroxaban. The later exhibit stable pharmacokinetics obviating the need for coagulation monitoring or dose titration, and they lack clinically significant food or drug interaction. Moreover, they offer another potential that includes fixed dosing, oral administration, and rapid onset of action. There are several concerns regarding potential harm, including an increased risk for hepatotoxicity, clinically significant bleeding, and acute coronary events. Therefore, additional trials and postmarketing surveillance will be needed.


2021 ◽  
Vol 27 ◽  
pp. 107602962110447
Author(s):  
Hongxia Li ◽  
Lei Zhang ◽  
Ming Xia ◽  
Chi Zhang ◽  
Tingbo Jiang

Background Novel oral anticoagulants and warfarin are widely used for stroke prevention in patients with atrial fibrillation. The anticoagulation status of patients receiving warfarin or rivaroxaban has been studied. In this study, we aimed to evaluate the effect of dabigatran and warfarin on preventing thrombin generation (TG). Methods This retrospective study enrolled 237 nonvalvular atrial fibrillation (NVAF) subjects treated with 110 mg dabigatran etexilate twice daily and 224 NVAF patients received adjusted-dose warfarin (international normalized ratio [INR] of 2 to 3)). Coagulation assays, prothrombin fragment 1  +  2 (F1+2), calibrated automated thrombogram, and thrombin–antithrombin complex (TAT) were detected at the steady state. Results Activated partial thromboplastin time (APTT), antithrombin III activity, fibrinogen, and lag time showed no difference between the two groups. Compared to the dabigatran group, prothrombin time and INR values were higher in the warfarin group (all P < .001). Thrombin time, endogenous thrombin potential, peak TG (Cmax), F1+2, and TAT were lower in the warfarin group. The inhibition of TG was still stronger in the warfarin group when the patients were divided into subgroups. Conclusion Conventional coagulation assays are suboptimal for assessing the coagulation status of dabigatran. TG could be used as supplementary assays to evaluate the anticoagulation effect of oral anticoagulants. Our results suggest that warfarin may inhibit TG more aggressively than dabigatran in patients regardless of age and kidney function.


Author(s):  
Eileen Fonseca ◽  
David R Walker ◽  
Jerrold Hill ◽  
Gregory P Hess

Background: Warfarin and dabigatran etexilate (DE) are oral anticoagulants used to reduce the risk of stroke among patients with nonvalvular atrial fibrillation (NVAF). This study examined whether hospital length of stay (LOS) differed for the two therapies. Methods: LOS was evaluated for patients hospitalized with a primary or secondary discharge diagnosis of atrial fibrillation (AF) between 1/1-3/31/2011, with DE or warfarin administered during hospitalization, and excluding patients with a valvular procedure. Patients were identified from a hospital Charge Detail Masters database, consisting of 184 hospitals. Differences in LOS by therapy were estimated using propensity score-matched samples selected by nearest neighbor matching within a caliper of 0.20 standard deviations of the logit, without replacement and a 2:1 match. Covariates used to estimate the propensity score included age, gender, CHADS 2 score, comorbid conditions and hospital attributes. LOS was also analyzed in patient subgroups identified by use of specific bridging agents (low-molecular weight heparin, unfractionated heparin, combination of the heparins, or no bridging agent) and a subset categorized as newly diagnosed NVAF. Results: Matched samples included 2,372 warfarin and 1,186 DE patients selected from 19,725 warfarin and 1,190 DE patients. Covariates used for the propensity score were not significantly different in the matched samples. LOS was 1.06 days shorter for DE compared to warfarin (DE: 6.16 days vs. warfarin: 7.22 days, p<0.01). In the 4 subgroups identified by choice of bridging agent, LOS was significantly shorter for DE in 3 (0.8 to 1.4 days, p<0.011), but not the fourth (0.9 day, p=0.3). In the subset of newly diagnosed NVAF, LOS was not significantly shorter for DE when AF was the primary discharge diagnosis (0.5 day, p=0.15), but was 2.47 days shorter for DE patients (p<0.01) when AF was a secondary discharge diagnosis. Limitations of the study were small sample sizes in some subgroups and potential of residual confounding. Conclusions: Among hospitalized patients with NVAF receiving an oral anticoagualant, patients receiving DE had a shorter length of stay compared to patients receiving warfarin.


2011 ◽  
Vol 27 (6) ◽  
pp. 258-265
Author(s):  
Joshua B Darnell ◽  
Erika L Kleppinger

Objective: To review, analyze, and critique dabigatran etexilate's approved uses as an anticoagulant. Data Sources: Literature searches were performed via MEDLINE, International Pharmaceutical Abstracts, and Google Scholar through February 2011, using the term dabigatran. Additional data were obtained from tertiary sources and prescribing information. Study Selection and Data Extraction: All published Phase 3 anticoagulation trials investigating dabigatran for currently approved indications were selected. Information from other anticoagulation trials investigating dabigatran was used for critiquing Phase 3 studies. Data Synthesis: Dabigatran etexilate has been evaluated in multiple clinical trials as an alternative to enoxaparin for prevention of venous thromboembolism in total hip and knee replacement surgeries. It has also been evaluated as an alternative to warfarin in stroke and systemic embolism prevention in patients with atrial fibrillation. Results have generally been positive, with few exceptions. The standard adult dose of dabigatran 150 mg twice daily, approved for use in the US for stroke prevention in nonvalvular atrial fibrillation, was found to be superior to warfarin in regard to occurrence rates of stroke or systemic embolism and hemorrhagic stroke. The occurrence rates of intracranial bleeding, life-threatening bleeding, and major or minor bleeding were lower with dabigatran 150 mg twice daily than with warfarin; however, the occurrence of gastrointestinal bleeding was significantly higher. Conclusions: With its numerous benefits, and despite its drawbacks, dabigatran remains a promising option for oral anticoagulation therapy.


2012 ◽  
Vol 116 (5) ◽  
pp. 1093-1096 ◽  
Author(s):  
Sarah T. Garber ◽  
Walavan Sivakumar ◽  
Richard H. Schmidt

Dabigatran etexilate is an oral anticoagulant that acts as a direct, competitive thrombin inhibitor. Large randomized clinical trials have shown higher doses of dabigatran (150 mg taken twice daily) to be superior to warfarin in terms of stroke and systemic embolism rates in patients with nonvalvular atrial fibrillation. As a result, in 2010 the US FDA approved the use of dabigatran for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Dabigatran is especially attractive in the outpatient setting because patients do not require routine monitoring with prothrombin times or international normalized ratios. To date, no effective reversal agent for dabigatran in the event of catastrophic hemorrhage has been identified. The authors report a case of an elderly patient, being treated with dabigatran for atrial fibrillation, who presented with a rapidly expanding intracranial hemorrhage after a ground-level fall. This case highlights an impending neurosurgical quandary of complications secondary to this new anticoagulation agent and suggests potential options for management.


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