Safety of Short-Term Use of Dabigatran or Rivaroxaban for Direct-Current Cardioversion in Patients With Atrial Fibrillation and Atrial Flutter

doi:10.1016/j.amjcard.2013.12.044

The American Journal of Cardiology

Volume 113, Issue 8, 15 April 2014, Pages 1362-1363

https://doi.org/10.1016/j.amjcard.2013.12.044 Get rights and content

Direct-current cardioversion (DCCV) for persistent atrial fibrillation or atrial flutter (AF) carries a risk of thromboembolic events (TEs). Therapeutic anticoagulation with warfarin is recommended for 3 to 4 weeks before and 4 weeks after DCCV to reduce TE; however, the safety of short-term anticoagulation with the novel oral anticoagulants (dabigatran and rivaroxaban) before DCCV has not been assessed. A retrospective cohort study was performed on all patients undergoing elective DCCV for AF at Northwestern Memorial Hospital from June 1, 2012 to September 30, 2013. Inclusion criteria included patients taking any of the novel oral anticoagulants for 21 to 60 days before DCCV and successful DCCV to sinus rhythm. Patients were monitored for a minimum of 60 days after DCCV to evaluate for TEs including stroke, transient ischemic attack, systemic emboli, and death. In total, 53 patients (47 men, 89%; age 65 ± 10 years, median 66) were evaluated. Agents used were dabigatran (30 patients, 57%) and rivaroxaban (23 patients, 43%) for an average of 38 ± 9 days. The mean CHADS₂ score was 1.2 ± 1.1 (score = 0, 26%; 1, 43%; 2, 17%; and >3, 13%). Eleven patients (21%) underwent a transesophageal echocardiography before their DCCV; all showed no thrombus. No patients were found to have episodes of TE within 60 days of DCCV. No patients were found to have major bleeding events. In conclusion, the use of short-term dabigatran or rivaroxaban therapy for DCCV of AF appears safe.

Section snippets

Methods

This study was approved by the Northwestern University Institutional Review Board. A standardized, retrospective, cohort study was performed on all patients undergoing elective DCCV for AF at Northwestern Memorial Hospital from June 1, 2012 to September 30, 2013. All patients had documented AF on electrocardiography previously and on the day of DCCV. Inclusion criteria included patients taking dabigatran or rivaroxaban for 21 to 60 days before DCCV and successful DCCV to sinus rhythm. Key

Results

Agents used were dabigatran 150 mg twice daily and rivaroxaban 20 mg/day for an average of 38 ± 9 days (range 21 to 56). Patient characteristics and prevalence of stroke risk factors are listed in Table 1. The mean CHADS₂ score was 1.2 ± 1.1 (Figure 1). Eleven patients (21%) underwent a transesophageal echocardiography before their DCCV; all showed no thrombus. Patients were monitored for a minimum of 60 days for TE as well as major bleeding. No patients were found to have TE, major bleeding

Discussion

Although NOACs have the potential benefit of providing therapeutic anticoagulation in patients with AF, there are limitations to these drugs. Renal disease must be considered, given the pharmacokinetics. Dabigatran and rivaroxaban have >80% and >60% renal excretion, respectively.6, 7, 8 In the RE-LY (randomized evaluation of long-term anticoagulation therapy) and ROCKET-AF (rivaroxaban once daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and

Disclosures

Dr. Passman receives speaking fees from Boehringer Ingelheim (Ingelheim am Rhein, Germany), Janssen Pharmaceuticals (Titusville, New Jersey), and Pfizer/BMS (Princeton, New Jersey and New York, New York).

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Cited by (37)

Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report
2018, Chest
Citation Excerpt :
However, patients with atrial flutter frequently present phases of AF alternated with phases of classical flutter or regular atrial rhythm.392-394 A systematic review on the thromboembolic risk associated with atrial flutter, including 52 articles, found that thromboembolic event rates after cardioversion varied from 0% to 6% with a follow-up from 1 week to 6 years.234,271,274,275,395-405 Echocardiographic studies reported prevalence of intra-atrial thrombi from 0% to 38% and a prevalence of spontaneous echo contrast up to 28%.392,393,403,406-415
The risk of stroke is heterogeneous across different groups of patients with atrial fibrillation (AF), being dependent on the presence of various stroke risk factors. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios.
Systematic literature reviews were conducted to identify relevant articles published from the last formal search perfomed for the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). The overall quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted, voted on, and revised until consensus was reached.
For patients with AF without valvular heart disease, including those with paroxysmal AF, who are at low risk of stroke (eg, CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)] score of 0 in males or 1 in females), we suggest no antithrombotic therapy. The next step is to consider stroke prevention (ie, oral anticoagulation therapy) for patients with 1 or more non-sex CHA₂DS₂-VASc stroke risk factors. For patients with a single non-sex CHA₂DS₂-VASc stroke risk factor, we suggest oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel; and for those at high risk of stroke (eg, CHA₂DS₂-VASc ≥ 2 in males or ≥ 3 in females), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest using a non-vitamin K antagonist oral anticoagulant drug rather than adjusted-dose vitamin K antagonist therapy. With the latter, it is important to aim for good quality anticoagulation control with a time in therapeutic range > 70%. Attention to modifiable bleeding risk factors (eg, uncontrolled BP, labile international normalized ratios, concomitant use of aspirin or nonsteroidal antiinflammatory drugs in an anticoagulated patient, alcohol excess) should be made at each patient contact, and HAS-BLED (hypertension, abnormal renal/liver function [1 point each], stroke, bleeding history or predisposition, labile international normalized ratio, elderly (0.65), drugs/alcohol concomitantly [1 point each]) score used to assess the risk of bleeding where high risk patients (≥ 3) should be reviewed and followed up more frequently.
Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF with ≥1 non-sex CHA₂DS₂-VASc stroke risk factor(s).
Influence of proton pump inhibitors on blood dabigatran concentrations in Japanese patients with non-valvular atrial fibrillation
2017, Journal of Arrhythmia
Dabigatran is a direct thrombin inhibitor used to decrease the risk of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Its prodrug, dabigatran etexilate (DE) is often co-administrated with a proton pump inhibitor (PPI) because of its adverse effects on the gastrointestinal tract. Drug-drug interactions between DE and PPIs in daily clinical practice have not been fully elucidated.
Changes in blood dabigatran concentration (DC) were investigated using the dilute thrombin time test in a randomized, open-label, two-period crossover study including 34 Japanese patients with NVAF receiving dabigatran therapy with or without PPI.
The average trough DC was significantly higher without PPI than with PPI (83 ± 42.3 vs. 55.5 ± 24.6 ng/mL, respectively; P < 0.001). Similarly, the average peak DC was significantly higher without PPI than with PPI (184.1 ± 107.7 vs. 124 ± 59.2 ng/mL, respectively; P = 0.0029). The average ratio of DC change at the trough and peak levels did not differ significantly among the three PPI types.
PPI administration significantly decreased the trough and peak DCs in patients with NVAF. Therefore, when prescribing PPIs for patients with NVAF in a clinical setting, the possibility that the bioavailability of dabigatran may decrease should be considered.
Non-vitamin K antagonist oral anticoagulants versus warfarin for cardioversion of atrial fibrillation in clinical practice: A single-center experience
2017, Journal of Arrhythmia
Citation Excerpt :
Other than those studies, few reports are available concerning the effects of NOAC usage on cardioversion in clinical practice. An investigation of 53 patients including 43 AF patients treated with dabigatran or rivaroxaban reported no patients with episodes of thromboembolic events within 60 days after EVC [19], but that study did not compare these patients’ results with those of patients treated with warfarin. In 2015, Coleman et al. reported that NOAC utilization in clinical practice in North America has now increased to one-third of ECV procedures with safety and effectiveness equal to those of warfarin [20].
Anticoagulation therapy with the vitamin K antagonist (VKA) warfarin has been demonstrated to reduce thromboembolic risk after electrical cardioversion (ECV). However, data concerning ECV with non-VKA oral anticoagulants (NOACs) is limited. The objective of this study was to determine the efficacy and safety of NOACs in patients undergoing ECV in a real-world clinical practice at a single center in Japan.
We retrospectively analyzed the data of 406 consecutive patients who underwent ECV for atrial fibrillation (AF) or flutter under anticoagulation with one of the three NOACs (n=149) or with a VKA (n=257).
The CHADS2 and HAS-BLED scores were significantly higher in the VKA group, whereas the NOACs group had a tendency toward greater spontaneous echo contrast grades. After ECV, ischemic stroke occurred in three patients of the VKA group and one patient in the NOAC group, all of whom had persistent AF, indicating no significant difference in the thromboembolic event rate within 30 days following ECV. No other thromboembolic events, major bleeding, or death occurred in either group. Among the NOAC and VKA patients in whom we newly introduced an oral anticoagulant to perform ECV, the number of days leading to ECV was significantly lesser for the NOAC patients.
NOACs may be used as an alternative to VKAs for ECV and may allow prompt ECV in clinical practices.
A new integrated strategy for direct current cardioversion in non-valvular atrial fibrillation patients using short term rivaroxaban administration: The MonaldiVert real life experience
2016, International Journal of Cardiology
Care Indicators in Patients with Atrial Fibrillation: Assessment of Sex Differences and Management of Clinical Problems
2016, Revista Espanola de Cardiologia
Evaluar mediante indicadores asistenciales las diferencias por sexo y el manejo de los problemas clínicos que presentan los pacientes que presentan fibrilación auricular.
Durante 5 meses se incluyó consecutivamente a todos los pacientes atendidos en las consultas de cardiología de 2 hospitales de tercer nivel por presentan un episodio de fibrilación auricular o un proceso clínico debido a ella.
Se incluyó a 533 pacientes (el 56,5% mujeres; media de edad, 70,5 ± 12,2 años), de los que el 24,3% eran menores de 65 años. Las mujeres tenían significativamente más problemas clínicos y un riesgo de embolia más elevado: CHADS₂ (insuficiencia cardiaca congestiva, hipertensión, edad, diabetes, ictus [doble]) (1,8 ± 1,2 frente a 1,5 ± 1,1; p = 0,001) y CHA₂DS₂-VASc (insuficiencia cardiaca congestiva, hipertensión, edad ≥ 75 [doble], diabetes, ictus [doble], enfermedad vascular y categoría de sexo [mujeres]) (3,7 ± 1,4 frente a 2,2 ± 1,4; p = 0,0001). Al 94% de los pacientes se los derivaba correctamente a cardiología, el 53,8% procedía de atención primaria u otros servicios del hospital y al 93,4% se le realizó o indicó una ecocardiografía. El tratamiento (antiarrítmico y antiembolígeno) se hace según las recomendaciones de las guías. El índice de Rosendaal en los 3 meses previos fue de 48,4 ± 37,4.
Uno de cada 4 pacientes que consultan por problemas derivados de la fibrilación auricular son jóvenes y las mujeres tienen más problemas clínicos y consultan más. A los pacientes se los deriva correctamente a cardiología, y la mayoría no procede de urgencias. Se indican la ecocardiografía y el tratamiento antiarrítmico y antiacoagulante tal como recomiendan las guías de práctica clínica. El control de la anticoagulación con fármacos antagonistas de la vitamina K es deficiente.
To assess sex differences and the management of clinical problems in patients with atrial fibrillation through the use of care indicators.
Over a 5-month period, the study included all consecutive patients attended in the cardiology outpatient clinics of 2 tertiary hospitals with an atrial fibrillation episode or a clinical process due to atrial fibrillation.
A total of 533 patients were included (56.5% women; mean age, 70.5 ± 12.2 years), of whom 24.3% were younger than 65 years. Women had significantly more clinical problems and a higher stroke risk: CHADS₂ (congestive heart failure, hypertension, age, diabetes, stroke [doubled]) (1.8 ± 1.2 vs 1.5 ± 1.1; P = .001) and CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥ 75 [doubled], diabetes, stroke [doubled]-vascular disease and sex category [female]) (3.7 ± 1.4 vs 2.2 ± 1.4; P = .0001). Referrals to the cardiology department were appropriate in 94% of the patients, the referral source was primary care or other hospital services in 53.8%, and echocardiography was performed or recommended in 93.4%. Treatment (antiarrhythmics and anticoagulants) was administered according to guideline recommendations. In the previous 3 months, the Rosendaal index was 48.4 ± 37.4.
One in every 4 patients seeking care for problems associated with atrial fibrillation are young; women have more clinical problems and seek care more frequently than men. Patients are correctly referred to the cardiology department and most are not referred from the emergency department. Echocardiography and antiarrhythmic and anticoagulant therapy were provided according to the recommendations of clinical practice guidelines. Vitamin K antagonists for anticoagulation therapy are underused.
Full English text available from: www.revespcardiol.org/en
Relation Between Dabigatran Concentration, as Assessed Using the Direct Thrombin Inhibitor Assay, and Activated Clotting Time/Activated Partial Thromboplastin Time in Patients With Atrial Fibrillation
2015, American Journal of Cardiology
Dabigatran is a direct thrombin inhibitor that has been approved for preventing stroke in patients with atrial fibrillation. In this study, we aimed to assess the associations between the dabigatran concentration (calculated through plasma-diluted thrombin time, as assessed using the Hemoclot assay) and the activated partial thromboplastin time (aPTT) and activated clotting time (ACT). We recruited 137 patients with atrial fibrillation who were receiving a normal dose of dabigatran (300 mg/d) or a reduced dose of dabigatran (220 mg/d, usually administered to patients who were elderly, had moderate renal dysfunction, or who were also receiving verapamil). We then assessed the aPTT, ACT, and Hemoclot results of the patients and calculated the plasma dabigatran concentration. The mean plasma concentration of dabigatran was 127 ± 88 ng/ml, although no significant differences in dabigatran concentration, ACT, or aPTT were observed when we compared the 2 doses of dabigatran (300 or 220 mg/d). The dabigatran concentration was within the therapeutic levels in most patients, although a high value (>300 ng/ml) was observed in several patients, which indicated a high risk of bleeding. The dabigatran concentration was strongly and positively correlated with ACT and aPTT (r = 0.87, p <0.001; and r = 0.76, p <0.001; respectively). Multivariate analysis revealed that verapamil use was independently associated with elevated dabigatran concentrations (p <0.001). Therefore, ACT and aPTT may be useful for bedside assessment of the anticoagulant activity of dabigatran, and verapamil use may be a risk factor for elevated dabigatran concentrations.

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Arrhythmias and Conduction DisturbancesSafety of Short-Term Use of Dabigatran or Rivaroxaban for Direct-Current Cardioversion in Patients With Atrial Fibrillation and Atrial Flutter

Section snippets

Methods

Results

Discussion

Disclosures

The effect of external electric currents on the heart; control of cardiac rhythm and induction and termination of cardiac arrhythmias

Circulation

Prevention of embolic events after cardioversion of atrial fibrillation. Current and evolving strategies

Arch Intern Med

Role of prophylactic anticoagulation for direct current cardioversion in patients with atrial fibrillation or atrial flutter

J Am Coll Cardiol

Anticoagulation for cardioversion of atrial fibrillation

Am J Cardiol

Design of a clinical trial for the assessment of cardioversion using transesophageal echocardiography (The ACUTE Multicenter Study). Steering and Publications Committees of the ACUTE Study

Am J Cardiol

Arrhythmias and Conduction Disturbances
Safety of Short-Term Use of Dabigatran or Rivaroxaban for Direct-Current Cardioversion in Patients With Atrial Fibrillation and Atrial Flutter