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13 June 2023: Articles  Saudi Arabia

Resolution of Left Ventricular Thrombus by Vitamin K Antagonist after Failed Treatment with Apixaban in Hemodialysis Patient: Case Report

Unusual or unexpected effect of treatment

Saleem Alenazi1ABFG, Faisal Alqarni2ABCDEFG*, Yara Aldajani2ABC, Abdullah Alzahrani2EG, Mawada Ahmed1BG

DOI: 10.12659/AJCR.940199

Am J Case Rep 2023; 24:e940199

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Abstract

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BACKGROUND: Left ventricular thrombus is a serious complication of numerous cardiovascular conditions. Anticoagulation with oral vitamin K antagonists such as warfarin is a standard treatment for left ventricular thrombus and is recommended to reduce the risk of embolization. Patients with cardiac conditions share comorbidities with patients with end-stage renal disease, and patients with advanced kidney disease are predisposed to atherothrombotic and thromboembolic complications. The efficacy of direct oral anticoagulants in patients with left ventricular thrombus has not been well studied.

CASE REPORT: A 50-year-old man had prior myocardial infarction, heart failure with reduced ejection fraction, diabetes, hypertension, atrial fibrillation, treated hepatitis B infection, and end-stage renal disease on hemodialysis. On regular outpatient follow-up with the cardiology clinic, a transthoracic echocardiogram was requested and revealed akinesia of the mid to apical anterior wall, mid to apical septum, and left ventricular apex, and large apical thrombus measuring 20×15 mm. Apixaban 5 mg orally twice daily was started. A transthoracic echocardiogram was done after 3 months and after 6 months, and the thrombus did not resolve. The apixaban was shifted to warfarin. The international normalized range was maintained at the therapeutic range (INR 2.0-3.0). After 4 months of receiving warfarin, echocardiography showed a resolution of the left ventricular thrombus.

CONCLUSIONS: We report a case of left ventricular thrombus that was successfully dissolved by warfarin after treatment with apixaban failed. This case challenges the general assumption of apixaban’s effectiveness in patients with end-stage renal disease on dialysis.

Keywords: Anticoagulants, Dialysis, Renal Insufficiency, Chronic, Thrombosis, Male, Humans, Middle Aged, Warfarin, Renal Dialysis, Kidney Failure, Chronic, Vitamin K

Background

Left ventricular (LV) thrombus is a serious complication of numerous cardiovascular conditions, such as myocardial infarction, dilated cardiomyopathy, and severe cardiac wall dysfunction [1]. Dilated cardiomyopathy is the most common etiology of LV thrombus [2]. LV thrombus is responsible for significant morbidity and mortality [2]. Anticoagulation with oral vitamin K antagonists such as warfarin is the standard treatment for LV thrombus and is recommended to reduce the risk of embolization [3]. Direct oral anticoagulants (DOACs) have been introduced as a replacement to oral vitamin K antagonists in a variety of indications for anticoagulation, such as preventing strokes and other thromboembolic events in non-valvular atrial fibrillation, as well as for the treatment of venous thromboembolism (pulmonary embolism and deep vein thrombosis) [4].

Patients with cardiac conditions share comorbidities with patients with end-stage renal disease (ESRD), and patients with advanced kidney disease are predisposed to atherothrombotic and thromboembolic complications [4,5]. The efficacy of DOACs in patients with LV thrombus has not been well studied. Furthermore, the evidence of DOACs is conflicting as to whether they are safe and effective in the ESRD population. We report a case of LV thrombus that was successfully dissolved by warfarin after treatment with apixaban failed.

Case Report

A 50-year-old man with diabetes, hypertension, paroxysmal atrial fibrillation, chronic kidney disease, coronary artery disease, heart failure with reduced ejection fraction, and treated hepatitis B infection was admitted to a tertiary hospital as a case of acute myocardial infarction and underwent successful revascularization with drug-eluting stent implantation. After the myocardial infarction, the patient was placed on dual antiplatelet therapy (aspirin 100 mg orally once daily and clopidogrel 75 mg orally once daily) for 24 months to prevent stent occlusion, followed by single antiplatelet therapy (aspirin 100 orally once daily). Three years after that admission, the chronic kidney disease progressed to ESRD and hemodialysis sessions were started. On regular outpatient follow-up with the cardiology clinic, the patient was free of symptoms, and a routine transthoracic echocardiogram was requested. His weight during that follow-up visit was 73 kg (body mass index of 26). Laboratory assessment revealed a hemoglobin level of 13.2 g/dL. His electrocardiographic result revealed normal sinus rhythm. The transthoracic echocardiogram showed akinesia of the mid to apical anterior wall, mid to apical septum, and LV apex, and large apical thrombus measuring (20×15 mm; Figure 1), and ejection fraction was 30%. Apixaban 5 mg orally twice daily was started.

The transthoracic echocardiogram was done after 3 months and after 6 months, and there was insignificant reduction in the size of the LV thrombus despite the patient compliance with apixaban (Figure 2). The apixaban was shifted to warfarin. The international normalized range was maintained at the therapeutic range (INR 2.0–3.0). After 4 months of receiving warfarin, the patient showed a complete resolution of LV thrombus (Figure 3).

Discussion

LV thrombus is one of the well-known complications of myocardial infarction and cardiomyopathy [1]. The risk of atherothrombotic and thromboembolic complications is even higher in the ESRD population [5]. Warfarin remains the safe and effective criterion standard of treatment for LV thrombus in the ESRD population and in the non-ESRD population, despite a lack of clear evidence in the ESRD population [6]. Apixaban is one of the DOACs. It is a direct inhibitor of factor Xa, which prevents the formation of thrombin, and has been approved for the prevention of stroke and other thromboembolic events in patients with atrial fibrillation and for the treatment of venous thromboembolism [4]. The introduction of DOACs, including apixaban, overcame many disadvantages associated with the use of warfarin [4]. Compared with warfarin, DOACs exert a superior pharmacokinetic profile due to the quick onset of action and therefore do not require bridge therapy with parenteral anticoagulants [4]. DOACs have fewer drug-drug interactions and food interactions. DOACs also have a predictable therapeutic effect requiring no monitoring [7]. Because patients with advanced kidney disease were underrepresented in the landmark clinical trials of DOACs, there are limited data about their efficacy and safety in these populations [8]. The 2019 Focused Update of the US Atrial Fibrillation Management Guidelines added the use of apixaban as an alternative to warfarin, with a class IIB recommendation, for anticoagulation for stroke prevention in atrial fibrillation patients with ESRD on hemodialysis [4]. In a multicenter cohort study of anticoagulation strategies for LV thrombus, DOAC treatment was associated with a higher risk of stroke or systemic embolism, compared with warfarin [9].

The presented case is the first report to demonstrate a failure of apixaban in resolution of LV thrombus and demonstrate complete resolution of LV thrombus after administration of warfarin in a patient with ESRD on dialysis.

Conclusions

We reported a case of LV thrombus that was successfully dissolved by warfarin after treatment with apixaban failed. This case challenges the general assumption of apixaban’s effectiveness in patients with ESRD on dialysis.

References:

1.. Satish M, Vukka N, Apala D, Left ventricular thrombus after acute decompensated heart failure in the setting of ischemic cardiomyopathy: Cureus, 2019; 11(4); e4537

2.. Talle MA, Buba F, Anjorin CO, Prevalence and aetiology of left ventricular thrombus in patients undergoing transthoracic echocardiography at the University of Maiduguri Teaching Hospital: Adv Med, 2014; 2014; 731936

3.. Iqbal H, Straw S, Craven TP, Stirling K, Direct oral anticoagulants compared to vitamin K antagonist for the management of left ventricular thrombus: ESC Heart Fail, 2020; 7(5); 2032-41

4.. Zirlik A, Bode C, Vitamin K antagonists: Relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients with atrial fibrillation.: J Thromb Thrombolysis, 2017; 43(3); 365-79

5.. Eikelboom J, Floege J, Thadhani R, Anticoagulation in patients with kidney failure on dialysis: factor XI as a therapeutic target: Kidney Int, 2021; 100(6); 1199-207

6.. Honan KA, Jogimahanti A, Khair T, An updated review of the efficacy and safety of direct oral anticoagulants in treatment of left ventricular thrombus: Am J Med, 2022; 135(1); 17-23

7.. Schwarb H, Tsakiris DA, New Direct Oral Anticoagulants (DOAC) and their use today: Dent J (Basel), 2016; 4(1); 5

8.. Hart RG, Eikelboom JW, Ingram AJ, Herzog CA, Anticoagulants in atrial fibrillation patients with chronic kidney disease: Nat Rev Nephrol, 2012; 8(10); 569-78

9.. Robinson AA, Trankle CR, Eubanks G, Off-label use of direct oral anticoagulants compared with warfarin for left ventricular thrombi: JAMA Cardiol, 2020; 5(6); 685-92

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923