Efficacy and Safety of Dabigatran Etexilate and Warfarin in “Real-World” Patients With Atrial Fibrillation

Larsen, Torben Bjerregaard; Rasmussen, Lars Hvilsted; Skjøth, Flemming; Due, Karen Margrete; Callréus, Torbjörn; Rosenzweig, Mary; Lip, Gregory Y.H.

doi:10.1016/j.jacc.2013.03.020

Cited by 390 publications

(325 citation statements)

References 33 publications

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“…When separating dabigatran into 110 and 150 mg BID, we confirmed previous registry‐based findings that lower‐dose dabigatran was associated with higher major bleeding risk when compared to warfarin 22, 23. This is in contrast to RE‐LY and partly in contrast to results from a Medicare claims analysis 19.…”

Section: Discussionsupporting

confidence: 84%

Major Bleeding Complications and Persistence With Oral Anticoagulation in Non‐Valvular Atrial Fibrillation: Contemporary Findings in Real‐Life Danish Patients

Lamberts

Stærk

Olesen

et al. 2017

JAHA

123

121

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BackgroundThe nonvitamin K antagonist oral anticoagulants have recently become available as an alternative to warfarin as stroke prophylaxis in atrial fibrillation, but data on real‐life patient experience, including bleeding risk, are lacking. Our objective was to compare major bleeding events and nonpersistence between the nonvitamin K antagonist oral anticoagulant apixaban and other nonvitamin K antagonist oral anticoagulants (dabigatran and rivaroxaban) and warfarin in a contemporary, nation‐wide cohort of patients with nonvalvular atrial fibrillation.Methods and ResultsOf 54 321 patients (median age, 73 years; 56% male; mean CHA 2 DS 2‐VASc score, 2.9), 7963, 6715, 15 413, and 24 230 patients initiated apixaban, rivaroxaban, dabigatran, and warfarin, respectively. Apixaban and rivaroxaban initiators were older, less often male, with higher HAS‐BLED and CHA 2 DS 2‐VASc scores compared with dabigatran and warfarin initiators. A total of 2418 patients (4.5%) experienced a major bleeding event over all available follow‐up. In this period, rivaroxaban (hazard ratio [HR] [95% CI], 1.49 [1.27–1.77]), dabigatran (HR, 1.17 [1.00–1.38]), and warfarin (HR, 1.23 [1.05–1.43]) users were significantly more likely to bleed than apixaban users. Findings were similar when restricted to the first 30 days after OAC initiation. Risk of nonpersistence was higher for dabigatran (HR, 1.45 [1.33–1.59]) and warfarin initiators (HR, 1.22 [1.12–1.33]), but not for rivaroxaban initiators (HR, 1.07 [0.96–1.20]) compared with apixaban initiators.ConclusionsIn a real‐world cohort of nonvalvular atrial fibrillation patients, apixaban had a lower adjusted major bleeding risk compared with rivaroxaban, dabigatran, and warfarin. Apixaban had a lower risk of nonpersistence compared with dabigatran and warfarin and similar risk compared with rivaroxaban.

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Section: Discussionsupporting

confidence: 84%

Major Bleeding Complications and Persistence With Oral Anticoagulation in Non‐Valvular Atrial Fibrillation: Contemporary Findings in Real‐Life Danish Patients

Lamberts

Stærk

Olesen

et al. 2017

JAHA

123

121

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“…[7][8][9]. Most of the current evidence from phase IV studies is on patients treated with dabigatran, since this was the first drug to be introduced on the market.…”

mentioning

confidence: 99%

“…Most of the current evidence from phase IV studies is on patients treated with dabigatran, since this was the first drug to be introduced on the market. The American and Danish administrative databases also include patients treated with warfarin, and, through propensity score matching, offer a comparison in the effectiveness and safety of the two therapeutic strategies [7,8]. Of note, the Medicare database reflects current practice in the United States, where the Food and Drug Administration approved dabigatran 150 mg twice daily (BID), with strict criteria for reduction to a 75 mg BID dose that is recommended for patients with severe renal impairment, defined by a creatinine clearance between 15 and 30 ml/min [7], while the European Medicines Agency (EMA) approved dabigatran 150 mg and 110 mg BID and established a contraindication for patients with creatinine clearance \30 ml/min.…”

mentioning

confidence: 99%

“…In terms of safety, the rates of major bleeding with dabigatran range from 2.2 to 4.3/100 pt-y, with small differences according to the dose in both phase III clinical trials and in phase IV studies [7][8][9][10][11][12]. RCTs and registries unanimously report very low rates of intracranial hemorrhages (ranging from 0.1 to 0.3/100 pt-y), which are also significantly decreased compared to warfarin [7,8,10,11].…”

mentioning

confidence: 99%

“…RCTs and registries unanimously report very low rates of intracranial hemorrhages (ranging from 0.1 to 0.3/100 pt-y), which are also significantly decreased compared to warfarin [7,8,10,11]. Conversely, dabigatran 150 mg BID is associated with a trend toward higher rates of gastrointestinal bleeding, although the difference with the comparator is not always statistically significant [7,8,10,11].…”

mentioning

confidence: 99%

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Direct oral anticoagulants in atrial fibrillation: can data from randomized clinical trials be safely transferred to the general population? Yes

Riva

Ageno²

2015

Intern Emerg Med

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Atrial fibrillation is the most common arrhythmia and is associated with significant morbidity and mortality. The current therapeutic options for patients at high thromboembolic risk include the vitamin K antagonists and the direct oral anticoagulants. These novel agents have been evaluated in more than 40,000 patients enrolled in four large randomized controlled trials for stroke prevention in non-valvular atrial fibrillation. When these results were pooled together, a greater efficacy profile, as well as a consistent reduction in life-threatening bleeding was shown in comparison to vitamin K antagonists. Randomized controlled trials offer the highest level of evidence on the efficacy and safety of an intervention; however, their results may not be directly applicable to the general population. The results of a number of post-marketing observational studies from the United States and Europe have been published. The results of these studies substantially confirm the findings of the randomized trials and show a favorable safety profile with the use of the direct oral anticoagulants even in unselected populations. Keywords Atrial fibrillation Á Factor Xa inhibitors Á Thrombin inhibitorsAtrial fibrillation (AF) is the most common dysrhythmia and is associated with significant morbidity and mortality [1]. The presence of AF increases a risk of ischemic stroke approximately five times the non dysrhythmic person, and cardio-embolic strokes carry the highest fatality rates [2]. The risk of stroke in patients with AF is proportional to the number of risk factors which are summarized by the CHA 2 DS 2 -VASc score: congestive heart failure; hypertension; age C75 years (doubled); diabetes mellitus; previous stroke or systemic embolism (doubled); vascular disease; age 65-74 years; and female gender [3]. The current therapeutic options for patients at high thromboembolic risk include the vitamin K antagonists (VKAs) and the novel direct oral anticoagulants (DOACs). VKAs have been the only available oral anticoagulants for about 70 years, but they have several drawbacks, which led to their underuse in real-life AF patients [4]. The DOACs, instead, besides the target-specific action on thrombin (dabigatran) or on factor Xa (apixaban, edoxaban and rivaroxaban) and also have a predictable dose-response, which allows fixed dose regimens without the need for routine laboratory monitoring.The DOACs have been evaluated in more than 40,000 patients enrolled in four large randomized controlled trials (RCTs) for stroke prevention in AF [5]. When these results are pooled together, a greater efficacy profile (19 % reduction in stroke or systemic embolism and 10 % reduction in all-cause mortality), as well as a consistent reduction in lifethreatening bleeding (52 % lower risk of intracranial hemorrhages) is shown in comparison to VKAs [5].RCTs offer the highest level of evidence of the efficacy and safety of an intervention; however, their results may not be directly applicable to the general population. In fact, RCTs have rigoro...

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Risk of Bleeding With Dabigatran in Atrial Fibrillation

et al. 2015

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IMPORTANCE It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice. OBJECTIVE To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data. DESIGN, SETTING, AND PARTICIPANTS In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011. EXPOSURES Dabigatran users (n = 1302) and warfarin users (n = 8102). MAIN OUTCOMES AND MEASURES We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities. RESULTS Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease. CONCLUSIONS AND RELEVANCE Dabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

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Efficacy and Safety of Dabigatran Etexilate and Warfarin in “Real-World” Patients With Atrial Fibrillation

Cited by 390 publications

References 33 publications

Major Bleeding Complications and Persistence With Oral Anticoagulation in Non‐Valvular Atrial Fibrillation: Contemporary Findings in Real‐Life Danish Patients

Major Bleeding Complications and Persistence With Oral Anticoagulation in Non‐Valvular Atrial Fibrillation: Contemporary Findings in Real‐Life Danish Patients

Direct oral anticoagulants in atrial fibrillation: can data from randomized clinical trials be safely transferred to the general population? Yes

Risk of Bleeding With Dabigatran in Atrial Fibrillation

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