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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 5  |  Issue : 2  |  Page : 30-32

Acute decompensated heart failure increases the anticoagulation effect of dabigatran: A case report


1 Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
2 Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China

Date of Submission16-Jul-2020
Date of Decision22-Oct-2020
Date of Acceptance21-Nov-2020
Date of Web Publication28-Jan-2021

Correspondence Address:
Dr. Mingfang Li
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijhr.ijhr_8_20

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  Abstract 

Dabigatran is a widely used non-Vitamin K antagonist oral anticoagulant and has demonstrated a better efficacy and safety profile compared to Vitamin K antagonists. However, in some specific situations, the bleeding risk of dabigatran will be much increased. A 76-year-old female atrial fibrillation patient with concomitant nonrheumatic mitral valve regurgitation and chronic heart failure was described. She was on dabigatran 110 mg twice a day. On day 2 after admission, the patient presented with acute decompensated heart failure, the creatinine clearance level markedly decreased from 40.9 mL/min to 23.1 mL/min, and the trough-activated partial thromboplastin time exceeded the detection range. In this clinical context, renal and coagulation function should be monitored closely to avoid severe adverse events, especially major bleeding. Low-molecular-weight heparin might be considered to be applied temporarily, and rivaroxaban may be prescribed in this condition. The ethical approval was waived by the institutional review board of our hospital owing to the retrospective nature of the study.

Keywords: Acute decompensated heart failure, anticoagulation effect, atrial fibrillation, case report, dabigatran, renal function


How to cite this article:
Geng L, Shi J, Li M, Chen M. Acute decompensated heart failure increases the anticoagulation effect of dabigatran: A case report. Int J Heart Rhythm 2020;5:30-2

How to cite this URL:
Geng L, Shi J, Li M, Chen M. Acute decompensated heart failure increases the anticoagulation effect of dabigatran: A case report. Int J Heart Rhythm [serial online] 2020 [cited 2021 Apr 12];5:30-2. Available from: https://www.ijhronline.org/text.asp?2020/5/2/30/308171


  Introduction Top


Atrial fibrillation (AF) is the most prevalent sustained cardiac rhythm disorder encountered in clinical practice.[1] The devastating complication of AF is ischemic stroke or systemic thromboembolism.[1] On the other hand, a high prevalence of AF has been found in patients with ischemic stroke, and AF is responsible for nearly one-third of all ischemic strokes.[2] Oral anticoagulants (OACs) are recommended to prevent thromboembolic events in high-risk AF patients. Dabigatran, as one of the non-Vitamin K antagonist OACs, could overcome some major weaknesses of Vitamin K antagonists including frequent monitoring of the prothrombin time international normalized ratio, frequent food and drug interactions, unpredictable dose responses, and slow onset and offset. Therefore, dabigatran has been widely used in clinical practice. Dabigatran has demonstrated a better efficacy and safety profile than Vitamin K antagonists.[3] However, in some specific situations, the bleeding risk of dabigatran will be much higher, and it is essential to explore a safer treatment strategy for these patients.


  Case Report Top


A 76-year-old female with a history of permanent AF and chronic heart failure for 2 years was on metoprolol, diuretics, and dabigatran 110 mg twice a day. She was admitted to the hospital due to progressive palpitation and the occurrence of two episodes of syncope. The body weight of the patient was 42.5 kg on admission. Her initial creatinine clearance (CrCl) estimated by the Cockroft-Gault formula was 40.9 mL/min, indicating moderately to severely decreased renal function. A prohormone of B-type natriuretic peptide level of 6515 pg/mL and left ventricular ejection fraction of 42% evaluated by echocardiography at admission indicated cardiac dysfunction. Initial coagulation examination showed an activated partial thromboplastin time (aPTT) level of 42.9 s (normal range: 14.5–34.5 s) when the plasma dabigatran concentration was at the trough.

On the morning of the 2nd day after admission, the patient presented with acute decompensated heart failure, developing severe dyspnea, profuse sweating, and pink bubble sputum cough. The patient's symptoms were relieved after intravenous administration of loop diuretics, sodium nitroprusside, cedilanid, and amiodarone for 3 h. Dabigatran was continued on the 2nd day for anticoagulation as usual. Renal and coagulation functions were reexamined on the 3rd day using fasting blood samples, the CrCl level decreased to 23.1 mL/min, and the aPTT level increased to >180 s when the plasma dabigatran concentration was at the trough. Considering that renal excretion of dabigatran is up to 80%, dabigatran was discontinued even without any signs of bleeding. To promote the excretion of dabigatran by the kidneys, diuretic therapy was strengthened by intravenously administering furosemide. A low dose of dalteparin sodium (5000 IU once a day, and the standard dose should be 8000 IU based on body weight) was applied subcutaneously every day after the aPTT level decreased to 56 s on the morning of the 4th day. Renal and coagulation function was monitored every 12 or 24 h. The CrCl level increased gradually (29.3, 31.3, 35.6, and 39.0 mL/min), and the aPTT level remained within the normal range. A standard dose of dalteparin sodium (4000 IU twice a day) was applied from the 7th day. The CrCl level was 37.7 mL/min, and the aPTT level was 37.7 s before discharge on the 16th day. Dalteparin sodium was switched to rivaroxaban 10 mg once a day since then. The patient showed no thromboembolic or bleeding events during hospitalization and 1-year follow-up. [Figure 1] shows the renal and coagulation functions in the course of the disease and the corresponding anticoagulation strategy. The ethical approval and written consent were waived by the institutional review board of our hospital owing to the retrospective nature of the study and routine treatments performed on this patient in clinical practice.
Figure 1: Renal and coagulation functions in the course of disease and the corresponding anticoagulation strategy. AF = Atrial fibrillation, aPTT = Activated partial thromboplastin time, bid = Twice a day, CrCl = Creatinine clearance, IV = Intravenous injection, LMWH = Low-molecular-weight heparin, qd = Once a day

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  Discussion Top


An elderly female AF patient with concomitant nonrheumatic mitral valve regurgitation and chronic heart failure was described. The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes mellitus, prior stroke or transient ischemic attack [doubled], vascular disease, age 65–74 years, female) score of this patient was 4, indicating a high risk of thromboembolism. The lower dose of dabigatran 110 mg twice a day was applied to this patient considering her age, moderate-to-severe renal dysfunction, and extremely low body weight. Low body mass index is suggested to be an independent risk factor for major bleeding in AF patients taking dabigatran.[4]

Dabigatran is a direct thrombin inhibitor. Due to its predictable pharmacodynamic effect, wide therapeutic window, and rapid onset of action, dabigatran could be used as a fixed-dose regimen without the need for routine coagulation tests.[5] However, coagulation monitoring is useful in certain clinical settings. The aPTT demonstrated curvilinearity with the dabigatran level, so in routine coagulation tests, the aPTT may provide an approximate assessment of dabigatran concentration and anticoagulant activity.[5]

Dabigatran has a renal excretion up to 80%. Therefore, any reduction in renal function may increase the plasma concentration of dabigatran and the bleeding risk. Periodic reassessment of renal function is essential,[6] especially in patients with acute decompensated heart failure as worsening renal function has a strong association with decompensated heart failure.[7] Neurohormonal and hemodynamic abnormalities and adverse drug effects of diuretics and vasodilators may contribute to this process.[7]

In this presented case, after an episode of acute decompensated heart failure, the CrCl level markedly decreased and was associated with a trough aPTT level exceeding the detection range, which reflected a strong anticoagulation effect of dabigatran. Following the recommendation from guidelines, dabigatran was discontinued, and parenteral anticoagulation was initiated in situations with acute renal failure.[8] The high probability of acute exacerbation of heart failure and the coexistence of renal insufficiency, underweight, and old age may make dabigatran a less preferable option for this patient. Rivaroxaban is another non-Vitamin K antagonist OAC available in the mainland of China. Rivaroxaban only has an approximate 36% renal excretion rate.[9] Therefore, in patients with moderate renal impairment, the plasma concentration of rivaroxaban is increased to a much lower level than that of dabigatran. Referring to the Japanese Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial fibrillation study,[10] a lower dose of rivaroxaban 10 mg once a day was prescribed to this patient.

This case report has shown that acute decompensated heart failure could increase the anticoagulation effect of dabigatran by worsening renal dysfunction. In this clinical setting, renal and coagulation function should be monitored closely to avoid severe adverse events, especially major bleeding. Low-molecular-weight heparin might be considered to be applied temporarily, as the dose could be easily adjusted in this situation. For patients with renal dysfunction and a high probability of acute decompensated heart failure, rivaroxaban may be prescribed in this condition. However, more accurate coagulation tests are needed in this clinical setting.

Institutional review board statement

The ethical approval is waived by the institutional review board of our hospital owing to the retrospective nature of the study and routine treatments performed on this patient in clinical practice.

Declaration of patient consent

The authors certify that they have obtained the appropriate patient consent form. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

The work was supported by the Construction Program of Jiangsu Provincial Clinical Research Center Support System (No. BL2014084).

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-962.  Back to cited text no. 1
    
2.
Yang X, Li S, Zhao X, Liu L, Jiang Y, Li Z, et al. Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China. BMC Neurol 2017;17:207.  Back to cited text no. 2
    
3.
Hernandez I, Zhang Y, Saba S. Comparison of the effectiveness and safety of apixaban, dabigatran, rivaroxaban, and warfarin in newly diagnosed atrial fibrillation. Am J Cardiol 2017;120:1813-9.  Back to cited text no. 3
    
4.
Lee CH, Lin TY, Chang SH, Chen CH, Hsu YJ, Hung KC, et al. Body mass index is an independent predictor of major bleeding in non-valvular atrial fibrillation patients taking dabigatran. Int J Cardiol 2017;228:771-8.  Back to cited text no. 4
    
5.
van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, et al. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010;103:1116-27.  Back to cited text no. 5
    
6.
Huisman MV, Lip GY, Diener HC, Brueckmann M, van Ryn J, Clemens A. Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: Resolving uncertainties in routine practice. Thromb Haemost 2012;107:838-47.  Back to cited text no. 6
    
7.
McCallum W, Tighiouart H, Testani JM, Griffin M, Konstam MA, Udelson JE, et al. Acute kidney function declines in the context of decongestion in acute decompensated heart Failure. JACC Heart Fail 2020;8:537-47.  Back to cited text no. 7
    
8.
Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018;39:1330-93.  Back to cited text no. 8
    
9.
Chin PK, Doogue MP. Long-term prescribing of new oral anticoagulants. Aust Prescr 2016;39:200-4.  Back to cited text no. 9
    
10.
Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – The J-ROCKET AF study. Circ J 2012;76:2104-11.  Back to cited text no. 10
    


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