Feasibility and Safety of Uninterrupted Dabigatran Therapy in Patients Undergoing Ablation for Atrial Fibrillation

Objective: To report an incident of a drug-induced exanthem during treatment with dabigatran in a patient without prior exposure to the drug. Case Summary: A 20-year-old white male was prescribed oral dabigatran 150 mg twice daily for thromboembolic prevention because of nonvalvular atrial fibrillation. After 2 weeks of dabigatran therapy, a raised, pruritic, erythematous rash developed on the patient's inner thigh and forearm. Upon discontinuation of dabigatran and initiation of oral corticosteroid treatment, the rash resolved. Dabigatran therapy was not readministered and thromboembolic prevention therapy with warfarin was instituted. Discussion: The clinical evidence for efficacy of dabigatran was derived largely from the RE-LY trial, which provided an open-label comparison with warfarin for the reduction of stroke and systemic embolism in nonvalvular atrial fibrillation. The most frequent adverse reactions leading to discontinuation of dabigatran were bleeding and gastrointestinal events. In the RE-LY study, drug hypersensitivity, allergic edema, anaphylactic reaction, and anaphylactic shock were reported in <0.1% of patients receiving dabigatran. Despite the low incidence of hypersensitivity reported in the RE-LY trial, the use of the Naranjo probability scale indicated a probable relationship between the rash and dabigatran therapy in this patient. Conclusions: Upon initiation of dabigatran therapy, surveillance for hypersensitivity reactions should be included as part of routine drug monitoring.

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Abstract 17642: Warfarin versus Dabigatran: The Coagulation Activity in the Left Atrium During Atrial Fibrillation Ablation

Circulation ◽

10.1161/circ.130.suppl_2.17642 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Naoaki Hashimoto ◽

Takanori Arimoto ◽

Yoshinori Yashiro ◽

Tadateru Iwayama ◽

Daisuke Ishigaki ◽

...

Keyword(s):

Atrial Fibrillation ◽

Left Atrium ◽

Warfarin Therapy ◽

Thromboembolic Events ◽

Coagulation Activity ◽

Af Ablation ◽

Heparin Administration ◽

Group 12 ◽

D Dimer ◽

Dabigatran Therapy

Background: Atrial fibrillation (AF) ablation is associated with the potential risk of periprocedural thromboembolic events. Previous studies suggested performing AF ablation with continuous warfarin reduced the risk of thromboembolic events, otherwise the safety and efficacy of periprocedural dabigatran was controversial. We aim to compare the differences of the coagulable state in the left atrium (LA) between the anticoagulation strategies. Methods: We divided 158 patients who underwent AF ablation into 3 groups: ablation with off warfarin (n=100, WF-off group), ablation with perioperative warfarin therapy (n=33, WF group), and ablation with dabigatran therapy (n=25, D group). Warfarin was stopped 1 day before the procedure in WF-off group. Uninterrupted warfarin therapy was used in WF group and interrupted only on the morning of the procedure with dabigatran in D group. During AF ablation, the blood samples from the LA obtained immediately after the trans-septal puncture before heparin administration in each groups. The D-dimer level and soluble fibrin monomer complex (SFMC) level in the LA were evaluated. Results: The prevalence of positive D-dimer (≥ 0.5 μg/ml) in the LA was observed 3% in WF group, 12% in D group, and 23% in WF-off group, respectively. SFMC levels in the LA were significantly lower in WF group compared with WF-off group (p<0.01). SFMC levels in D group tended to be higher compared with WF group, but lower compared with WF-off group. Conclusions: The coagulation activity in the LA was lower with perioperative warfarin therapy than with dabigatran therapy. Even transient interruption of anticoagulant therapy may be associated with hypercoagulable status in the LA.

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The effect of routine preoperative interruption of dabigatran therapy on coagulation parameters and dabigatran plasma levels in a mixed surgical population

Anaesthesia and Intensive Care ◽

10.1177/0310057x19841009 ◽

2019 ◽

Vol 47 (2) ◽

pp. 183-188 ◽

Cited By ~ 2

Author(s):

Oliver F Brett ◽

Christian N Brett ◽

Paul KL Chin

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Elective Surgery ◽

Potential Utility ◽

Preoperative Period ◽

Clotting Time ◽

Preoperative Management ◽

Reversal Agent ◽

Coagulation Tests ◽

Dabigatran Therapy

Summary Dabigatran is an oral anticoagulant used for atrial fibrillation and venous thromboembolism. While an effective antibody reversal agent is available, its cost precludes routine use and the mainstay of preoperative management is timely dabigatran interruption. Unlike warfarin, there are no universally accepted protocols for interruption of dabigatran in the preoperative period and there is uncertainty around the interpretation of standard coagulation tests in the presence of dabigatran. We performed a prospective, observational pilot study in patients presenting for elective surgery to examine: 1) the preoperative plasma dabigatran concentrations on day of surgery associated with the local dabigatran interruption protocol, 2) the potential utility of dabigatran concentrations on day of surgery, and 3) the utility of standard coagulation tests in determining whether dabigatran concentrations were below a ‘safe’ threshold for surgery. We recruited patients presenting to pre-admission clinics for elective surgery. Dabigatran concentrations below 30 µg/L were considered adequate for proceeding with surgery. Data were obtained and analysed from 21 patients with a median (range) age of 70 (20–86) years. Median (range) dabigatran concentrations on the day of surgery were 5 (0–59) µg/L. Two patients had day of surgery concentrations exceeding 30 µg/L. Of the standard coagulation tests examined, only the thrombin clotting time (TCT) was abnormal for these two patients. Our interruption protocol was associated with safe dabigatran concentrations in most patients on the day of surgery. A minority of patients had dabigatran concentrations above the safe threshold, which were detectable by abnormal TCT results.

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Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation

Thrombosis and Haemostasis ◽

10.1160/th14-11-0954 ◽

2015 ◽

Vol 113 (06) ◽

pp. 1247-1257 ◽

Cited By ~ 99

Author(s):

Franziska Ebertz ◽

Kati Förster ◽

Vera Gelbricht ◽

Franziska Michalski ◽

Christina Köhler ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Treatment Discontinuation ◽

Intention To Treat ◽

Daily Care ◽

Kaplan Meier ◽

Relative Safety ◽

Ischaemic Attack ◽

Dabigatran Therapy

summaryThe effectiveness and safety of dabigatran for stroke prevention in atrial fibrillation (SPAF) demonstrated in RE-LY needs to be confirmed in daily care. To evaluate treatment persistence, effectiveness and safety of dabigatran therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 2,500 patients on novel oral anticoagulants in daily care. Between October 1, 2011 and February 28, 2013, a total of 341 SPAF patients receiving dabigatran were enrolled. The combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.93/100 patient-years in the intention-to-treat analysis (95%-CI 1.6–4.9) and at 1.9/100 patient-years in the on treatment analysis (events within three days after last intake). On-treatment rates were higher in patients selected for 110 mg dabigatran (n=183) BID compared to the 158 patients selected for 150 mg BID (2.88 [95% CI 1.16–5.93] vs 0.86/100 patient-years [95% CI 0.10, 3.12]). On treatment, major bleeding occurred at a rate of 2.3/100 patient-years and numerically more often in patients receiving the 110 mg BID dose compared to the 150 mg BID dose (2.9 vs 1.7/100 patient-years). Dabigatran treatment discontinuation occurred in a total of 124 patients during follow-up (25.8 per 100 patient-years in Kaplan Meier analysis). Main reasons for treatment discontinuation were nonbleeding side effects. Our data contribute to the confirmation of effectiveness and relative safety of dabigatran in unselected patients in daily care. However, discontinuation rates are not lower than those reported for patients treated with vitamin K antagonists.

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