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Fatal stroke following treatment with apixaban in a patient with atrial fibrillation and left atrial appendage thrombus
International Journal of Cardiology 214 (2016) 131–132
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Fatal stroke following treatment with apixaban in a patient with atrial fibrillation and left atrial appendage thrombus Ashkan Eftekhari a,⁎, Dorte Damgaard b, Erik L. Grove a,c a b c
Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus, Denmark Department of Neurology, Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus, Denmark Faculty of Health, Instititue of Clinical Medicine, Aarhus University, Denmark
a r t i c l e
i n f o
Article history: Received 29 February 2016 Accepted 19 March 2016 Available online 24 March 2016
1. Introduction Atrial fibrillation increases the risk of ischemic stroke 4–5 fold [1] and doubles the mortality independently of other vascular risk factors [2]. The vast majority (N 90%) of thrombi associated with atrial fibrillation originate from the left atrial appendage [3]. The direct factor Xa inhibitor apixaban is superior to warfarin in terms of stroke prevention with a lower risk of bleeding and mortality [4]. 2. Case story A previously healthy 63-year old man with 3–4 weeks of dyspnea (New York Heart Association functional class III) and newly onset atrial fibrillation was admitted. Echocardiography revealed severely decreased left ventricular ejection fraction (10%), dilated left ventricle (60 mm) and normal valve function. Standard dose apixaban (5 mg × 2) was initiated at the time of admission. Due to rapid heart rate (160–170 bpm) and congestive heart failure, digitalis and diuretics were administered, and low-dose ramipril (1.25 mg × 1) was added. Coronary angiography was normal. Transoesophageal echocardiography (TEE) revealed massive thrombus formation (Fig. 1 and Video
⁎ Corresponding author at: Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark. E-mail address: [email protected] (A. Eftekhari).
http://dx.doi.org/10.1016/j.ijcard.2016.03.147 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
1) in the LAA. Hence, we abstained from cardioversion. After 5 days, the patient was haemodynamically stabilized with normal blood pressure (105/60 mm Hg and atrial fibrillation with a heart rate of 90–100 bpm). Discharge was scheduled with subsequent close follow-up at the local heart failure out-patient clinic with planned control TEE after 3 weeks to ensure regression of the LAA thrombus. Prior to discharge, hemiparesis in the left extremities suddenly occurred, and acute stroke was suspected. The patient was promptly transferred to the neurological department, and magnetic resonance imaging of the brain (Fig. 2) revealed a large infarct in more than half of the territory of the right middle cerebral artery. Due to the size of the infarction and treatment with a non-vitamin K antagonist oral anticoagulant, we abstained from acute thrombolytic and endovascular therapy because of the risk of intracranial hemorrhage. Apixaban was replaced by Aspirin (75 mg × 1) and low-dose dalteparin (5.000 IU × 1). After 3 days, the patient became subconscious and computed tomography revealed cerebral edema. The patient deceased later that evening (after 8 days of hospitalization in total) due to cerebral incarceration.
3. Discussion NOACs are generally safe [5] and in patients with heart failure and atrial fibrillation, apixaban is superior to warfarin regarding both efficacy and safety [6]. However, previous case reports in patients with a verified LAA thrombus show conflicting results [7,8], as both resolution of the thrombus and ischemic stroke has been reported. Nothwithstanding the choice of anticoagulant therapy, initiation of treatment may mobilize a LAA thrombus. In the patient, the thrombus was very mobile (Video 1), and therefore possibly susceptible to be released into the systemic circulation. Moreover, in patients with severe heart failure, intestinal absorption of NOACs may be impaired [9], which is not easy to monitor with routine hospital laboratory assays. Therefore, initial anticoagulation with low-molecular heparin may thus be preferred in patients with a visible thrombus and/or severe congestive heart failure to ensure full anticoagulation in the acute phase. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2016.03.147.
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A. Eftekhari et al. / International Journal of Cardiology 214 (2016) 131–132
Conflict of interest ELG has received speaker honoraria from AstraZeneca, Baxter, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer and has participated in advisory board meetings for AstraZeneca, Bayer, Boehringer Ingelheim and Bristol-Myers Squibb. DD has received speaker honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer and has participated in advisory board meeting for AstraZeneca. References
Fig. 1. Transoesophageal echocardiography of the left atrial appendage showing extensive thrombus formation. Still picture of Video 1.
Fig. 2. Magnetic resonance imaging of the brain. Large ischemic area in the right hemisphere.
[1] P.A. Wolf, R.D. Abbott, W.B. Kannel, Atrial fibrillation as an independent risk factor for stroke: the Framingham study, Stroke 22 (1991) 983–988. [2] E.J. Benjamin, P.A. Wolf, R.B. D'Agostino, H. Silbershatz, W.B. Kannel, D. Levy, Impact of atrial fibrillation on the risk of death: the Framingham heart study, Circulation 98 (1998) 946–952. [3] J.L. Blackshear, J.A. Odell, Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation, Ann. Thorac. Surg. 61 (1996) 755–759. [4] C.B. Granger, J.H. Alexander, J.J. McMurray, R.D. Lopes, E.M. Hylek, M. Hanna, et al., Apixaban versus warfarin in patients with atrial fibrillation, N. Engl. J. Med. 365 (2011) 981–992. [5] R. Providencia, E.L. Grove, S. Husted, S. Barra, S. Boveda, J. Morais, A meta-analysis of phase III randomized controlled trials with novel oral anticoagulants in atrial fibrillation: comparisons between direct thrombin inhibitors vs factor Xa inhibitors and different dosing regimens, Thromb. Res. 134 (2014) 1253–1264. [6] J.J. McMurray, J.A. Ezekowitz, B.S. Lewis, B.J. Gersh, D.S. van, J. Amerena, et al., Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial, Circ. Heart Fail. 6 (2013) 451–460. [7] T. Kawakami, H. Kobayakawa, H. Ohno, N. Tanaka, H. Ishihara, Resolution of left atrial appendage thrombus with apixaban, Thromb. J. 11 (2013) 26. [8] M. Ohyagi, K. Nakamura, M. Watanabe, H. Fujigasaki, Embolic stroke during apixaban therapy for left atrial appendage thrombus, J. Stroke Cerebrovasc. Dis. 24 (2015) e101–e102. [9] D. Berkowitz, M.N. Croll, W. Likoff, Malabsorption as a complication of congestive heart failure, Am. J. Cardiol. 11 (1963) 43–47.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Fatal stroke following treatment with apixaban in a patient with atrial fibrillation and left atrial appendage thrombus Ashkan Eftekhari a,⁎, Dorte Damgaard b, Erik L. Grove a,c a b c
Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus, Denmark Department of Neurology, Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus, Denmark Faculty of Health, Instititue of Clinical Medicine, Aarhus University, Denmark
a r t i c l e
i n f o
Article history: Received 29 February 2016 Accepted 19 March 2016 Available online 24 March 2016
1. Introduction Atrial fibrillation increases the risk of ischemic stroke 4–5 fold [1] and doubles the mortality independently of other vascular risk factors [2]. The vast majority (N 90%) of thrombi associated with atrial fibrillation originate from the left atrial appendage [3]. The direct factor Xa inhibitor apixaban is superior to warfarin in terms of stroke prevention with a lower risk of bleeding and mortality [4]. 2. Case story A previously healthy 63-year old man with 3–4 weeks of dyspnea (New York Heart Association functional class III) and newly onset atrial fibrillation was admitted. Echocardiography revealed severely decreased left ventricular ejection fraction (10%), dilated left ventricle (60 mm) and normal valve function. Standard dose apixaban (5 mg × 2) was initiated at the time of admission. Due to rapid heart rate (160–170 bpm) and congestive heart failure, digitalis and diuretics were administered, and low-dose ramipril (1.25 mg × 1) was added. Coronary angiography was normal. Transoesophageal echocardiography (TEE) revealed massive thrombus formation (Fig. 1 and Video
⁎ Corresponding author at: Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark. E-mail address: [email protected] (A. Eftekhari).
http://dx.doi.org/10.1016/j.ijcard.2016.03.147 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
1) in the LAA. Hence, we abstained from cardioversion. After 5 days, the patient was haemodynamically stabilized with normal blood pressure (105/60 mm Hg and atrial fibrillation with a heart rate of 90–100 bpm). Discharge was scheduled with subsequent close follow-up at the local heart failure out-patient clinic with planned control TEE after 3 weeks to ensure regression of the LAA thrombus. Prior to discharge, hemiparesis in the left extremities suddenly occurred, and acute stroke was suspected. The patient was promptly transferred to the neurological department, and magnetic resonance imaging of the brain (Fig. 2) revealed a large infarct in more than half of the territory of the right middle cerebral artery. Due to the size of the infarction and treatment with a non-vitamin K antagonist oral anticoagulant, we abstained from acute thrombolytic and endovascular therapy because of the risk of intracranial hemorrhage. Apixaban was replaced by Aspirin (75 mg × 1) and low-dose dalteparin (5.000 IU × 1). After 3 days, the patient became subconscious and computed tomography revealed cerebral edema. The patient deceased later that evening (after 8 days of hospitalization in total) due to cerebral incarceration.
3. Discussion NOACs are generally safe [5] and in patients with heart failure and atrial fibrillation, apixaban is superior to warfarin regarding both efficacy and safety [6]. However, previous case reports in patients with a verified LAA thrombus show conflicting results [7,8], as both resolution of the thrombus and ischemic stroke has been reported. Nothwithstanding the choice of anticoagulant therapy, initiation of treatment may mobilize a LAA thrombus. In the patient, the thrombus was very mobile (Video 1), and therefore possibly susceptible to be released into the systemic circulation. Moreover, in patients with severe heart failure, intestinal absorption of NOACs may be impaired [9], which is not easy to monitor with routine hospital laboratory assays. Therefore, initial anticoagulation with low-molecular heparin may thus be preferred in patients with a visible thrombus and/or severe congestive heart failure to ensure full anticoagulation in the acute phase. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2016.03.147.
132
A. Eftekhari et al. / International Journal of Cardiology 214 (2016) 131–132
Conflict of interest ELG has received speaker honoraria from AstraZeneca, Baxter, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer and has participated in advisory board meetings for AstraZeneca, Bayer, Boehringer Ingelheim and Bristol-Myers Squibb. DD has received speaker honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer and has participated in advisory board meeting for AstraZeneca. References
Fig. 1. Transoesophageal echocardiography of the left atrial appendage showing extensive thrombus formation. Still picture of Video 1.
Fig. 2. Magnetic resonance imaging of the brain. Large ischemic area in the right hemisphere.
[1] P.A. Wolf, R.D. Abbott, W.B. Kannel, Atrial fibrillation as an independent risk factor for stroke: the Framingham study, Stroke 22 (1991) 983–988. [2] E.J. Benjamin, P.A. Wolf, R.B. D'Agostino, H. Silbershatz, W.B. Kannel, D. Levy, Impact of atrial fibrillation on the risk of death: the Framingham heart study, Circulation 98 (1998) 946–952. [3] J.L. Blackshear, J.A. Odell, Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation, Ann. Thorac. Surg. 61 (1996) 755–759. [4] C.B. Granger, J.H. Alexander, J.J. McMurray, R.D. Lopes, E.M. Hylek, M. Hanna, et al., Apixaban versus warfarin in patients with atrial fibrillation, N. Engl. J. Med. 365 (2011) 981–992. [5] R. Providencia, E.L. Grove, S. Husted, S. Barra, S. Boveda, J. Morais, A meta-analysis of phase III randomized controlled trials with novel oral anticoagulants in atrial fibrillation: comparisons between direct thrombin inhibitors vs factor Xa inhibitors and different dosing regimens, Thromb. Res. 134 (2014) 1253–1264. [6] J.J. McMurray, J.A. Ezekowitz, B.S. Lewis, B.J. Gersh, D.S. van, J. Amerena, et al., Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial, Circ. Heart Fail. 6 (2013) 451–460. [7] T. Kawakami, H. Kobayakawa, H. Ohno, N. Tanaka, H. Ishihara, Resolution of left atrial appendage thrombus with apixaban, Thromb. J. 11 (2013) 26. [8] M. Ohyagi, K. Nakamura, M. Watanabe, H. Fujigasaki, Embolic stroke during apixaban therapy for left atrial appendage thrombus, J. Stroke Cerebrovasc. Dis. 24 (2015) e101–e102. [9] D. Berkowitz, M.N. Croll, W. Likoff, Malabsorption as a complication of congestive heart failure, Am. J. Cardiol. 11 (1963) 43–47.