Persistent Left Atrial Appendage Thrombus With Use of Rivaroxaban

Introduction

Warfarin has been the mainstay anticoagulant for patients with a left atrial appendage (LAA) thrombus for decades. The novel oral anticoagulants (NOACs), starting with FDA approval of rivaroxaban in 2011, have been replacing warfarin in recent years. There are many situations in which the favorability of rivaroxaban over warfarin is unknown, such as mechanical heart valves, left ventricular apical thrombus, and LAA thrombus. We report 3 patients with persistent LAA thrombus while taking rivaroxaban for at least 4 weeks. 

Case Series

Patient #1:

A 72-year-old woman with noninsulin-dependent diabetes mellitus underwent initial transesophageal echocardiogram (TEE) with plans for electrical cardioversion because of recent onset symptomatic atrial fibrillation. The patient had normal left ventricular systolic function, moderate mitral regurgitation, a mildly dilated left atrium, and a small thrombus in the left atrial appendage. She was prescribed metoprolol and digoxin for rate control. Rivaroxaban 20 mg daily (creatinine clearance [CrCL] 120 ml/min) was used for prevention of systemic embolization, which the patient took reliably. She was not taking any other medications that interact with rivaroxaban. Forty-two days later, a TEE was repeated prior to planned repeat cardioversion. It showed a persistent thrombus in the LAA. The size was unchanged. She has not experienced any embolic events.

Patient #2:

A 73-year-old woman with noninsulin-dependent diabetes mellitus, hypertension, and heart failure with mildly reduced left ventricular ejection fraction (40-45%) secondary to coronary artery disease was scheduled for elective electrical cardioversion of symptomatic persistent atrial fibrillation. In addition to a mildly reduced ejection fraction, the patient was found with mild mitral regurgitation, a moderately enlarged left atrium, spontaneous echo contrast in the left atrium, and a large LAA thrombus on TEE. Her international normalized ratio (INR) had been labile while taking warfarin, so the patient was changed to rivaroxaban 20 mg daily (CrCL 120 ml/min). The patient was not taking any medications that interfere with rivaroxaban. After 41 days of reliably taking rivaroxaban, TEE was repeated and showed persistence of the thrombus, at a reduced size. INR was available at time of repeat TEE and was 1.63, supporting her medications adherence. She has not experienced any embolic events.

Patient #3:

A 77-year-old man with history of prior tobacco use, transient ischemic attack, and ischemic cardiomyopathy with severely reduced left ventricular ejection fraction (<20%) was admitted with recent onset worsening dyspnea, and found with an acute exacerbation of congestive heart failure and new onset atrial fibrillation. The patient was treated with intravenous diuretics and medically optimized with a beta-blocker, ACE inhibitor, and aldosterone antagonist. He remained symptomatic with minimal exertion, so a TEE followed by electrical cardioversion to restore sinus rhythm and improve heart failure symptoms was planned. In addition to his known cardiomyopathy, the patient was found with mild-moderate mitral regurgitation, a moderately dilated left atrium, mild spontaneous echo contrast throughout the left atrium, and a small thrombus in the left atrial appendage. The patient was anticoagulated with rivaroxaban 15 mg daily (CrCL 45 ml/min). The patient was not taking any medications that interfere with rivaroxaban. After 63 days of reliably taking rivaroxaban, TEE was repeated, showing persistence of spontaneous echo contrast and a small thrombus in the left atrial appendage. He has not experienced any embolic events.

Discussion

Rivaroxaban, a direct factor Xa inhibitor, gained FDA approval in November 2011 for stroke prevention in patients with non-valvular atrial fibrillation based on the ROCKET AF trial.¹ Mechanistically, this medication is unique from the prior standard of care, warfarin, which is a vitamin K antagonist (VKA) that blocks multiple coagulation factors (factors II, VII, IX, and X). Guidelines recommend that one of the NOACs, including rivaroxaban, be considered in preference to VKA for stroke prevention in patients with non-valvular atrial fibrillation.² 

Although patients with planned electrical or chemical cardioversion were excluded from the ROCKET AF trial, some patients (<1%) did undergo either electrical/chemical cardioversion or atrial fibrillation ablation during the trial period. Findings of TEE in these patients, including the presence or absence of LAA clot, were not recorded.³ Over 80% of LAA thrombi have been shown to resolve with 4 weeks of therapeutic warfarin anticoagulation.⁴ If a patient is found with a LAA thrombus, recommendations support using 3 weeks of warfarin (goal INR 2.0-3.0) prior to cardioversion without the need to perform a repeat TEE, and at least 4 weeks of anticoagulation after.⁵ Because of limited experience with rivaroxaban in this scenario, a repeat TEE was performed prior to the planned cardioversion in our 3 patients. 

Conclusion

We report the findings of 3 patients with nonvalvular atrial fibrillation and persistent LAA thrombus while reliably taking rivaroxaban for at least 4 weeks. The drug has never been studied in this setting. Although there were no embolic events in these 3 patients, caution is warranted until further studies are completed. If the medication is utilized in patients with a LAA thrombus, a repeat TEE prior to elective cardioversion is advised. The X-TRA trial, a multicenter study using rivaroxaban in patients with nonvalvular atrial fibrillation found to have left atrial or left atrial appendage thrombus, is currently enrolling patients.

Disclosures: The authors have no conflicts of interests to report regarding the content herein.   

References

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