Rivaroxaban for treatment of intraventricular thrombus in Chagas disease

Abstract

Chagas disease leads to congestive heart failure, apical aneurysm, and may cause stroke or systemic embolism for intraventricular thrombus. We present a case of a 61-year-old man admitted for stroke 5 months after a renal embolism. An intraventricular thrombus was observed, probably the source of the cerebral and renal embolisms. The patient refused warfarin and rivaroxaban was used instead. After 40 days of treatment the thrombus had dissolved, after 20 months of regular use of rivaroxaban no more embolic events were observed. The use of rivaroxaban was effective in preventing embolic events in Chagas disease and intraventricular thrombus.

<Learning objective: Warfarin is recommended for stroke prevention in patients with Chagas disease and left ventricular dysfunction or apical aneurysm, even in the absence of thrombus. None of the new oral anticoagulants is recommended in this context. Rivaroxaban was safe and effective in preventing embolic events in a patient with Chagas disease and a ventricular thrombus.>

Introduction

Rivaroxaban is an oral factor Xa inhibitor and it is approved for prevention of stroke in non-valvular atrial fibrillation (AF) patients [1]. Chagas disease is common in Brazil and it leads to congestive heart failure; 37% of the patients also have apical aneurysm and 11% have intraventricular thrombus, leading to stroke or systemic embolism risk of 4.4% per year [2], [3]. Warfarin is the only approved therapy to prevent stroke in these patients, but rivaroxaban may be used if warfarin is contraindicated although there have been no randomized trials [4].

This is a case of stroke caused by a ventricular thrombus treated with rivaroxaban as the patient refused warfarin and in 40 days of treatment the thrombus had dissolved.

Case report

This case concerns a 61-year-old white man, with known Chagas disease since 1993 but without symptoms until 2007 when he underwent coronary angioplasty, and implantable electric defibrillator for ventricular tachycardia and coronary artery disease. The following year he was diagnosed with AF and warfarin was initiated. The treatment lasted only a month because the patient refused to undergo regular testing for international normalized ratio (INR). Subsequently, clopidogrel and aspirin were initiated. He remained stable for 3 years. In 2011, the patient was hospitalized for acute heart failure, left ventricular ejection fraction (LVEF) at 30%, was submitted to a resynchronization device. For two more years he had no cardiovascular symptoms. On the other hand, he was having severe dysphagia with loss of weight and was proposed surgery for chagasic megaesophagus. The procedure was performed on March 23, 2013, and the patient had renal embolism on the 5th post-operative day. At this time rivaroxaban 20 mg was introduced. He took the pill for 2 months and stopped by himself.

On August 18, 2013 he was admitted for a stroke within 15 min of symptoms: left hemiparesis, left ataxia, and dysarthria, US National Institutes of Health Stroke Scale International: 6. Initial tomography showed normal results (Fig. 1A and B); thus, the patient received alteplase after 30 min of admission. Complete recovery was observed, modified Rankin Scale after 3 months: 1.

Fig. 1.

(A) Normal computer tomography at admission. (B) Computer tomography 48 h after admission: Left cerebellar infarction of posterior brain circulation.

On August 19, 2013 echocardiography showed left atrium (LA): 44 mm, LVEF: 38%, left ventricular diastolic (LVD): 60 mm, left ventricular systolic (LVS): 48 mm, left ventricle (LV): generalized hypokinesia with thrombus 12.39 mm × 22.95 mm, apical (Fig. 2).

Fig. 2.

Echocardiography with apical thrombus. LA, left atrium; LV, left ventricle.

Aspirin 325 mg was used and a tomography was repeated after 10 days, as the ischemic cerebral area was extensive. There was no signal of hemorrhage, so warfarin was indicated but the patient refused it once again, he was not going to undergo regular testing for INR. We explained that the only approved therapy was warfarin and rivaroxaban might be used in an off-label indication. The patient agreed to off-label use and rivaroxaban 20 mg was initiated.

After 50 days we repeated the echocardiogram: 10/09/13: LA: 46 mm, LVEF: 37%, LVD: 60 mm, LVS: 47 mm, LV: generalized hypokinesia without thrombus (Fig. 3).

Fig. 3.

Echocardiography without thrombus. LA, left atrium; LV, left ventricle.

To date, May 21, 2015, the patient has been asymptomatic and no more embolic events were observed.

Discussion

Warfarin is a drug with great use over the past 60 years and the industry has been looking for a substitute. Warfarin reduces the risk of stroke by 64% in patients with AF but it has important limitations. Because of its unpredictable anticoagulant effect, multiple drug and food interactions, and narrow therapeutic index, warfarin requires routine coagulation monitoring and frequent dose adjustment to maintain the INR in the target range of 2–3 [5]. Patient adherence may be problematic, and about 70–80% of patients with AF admitted to stroke units had not used oral anticoagulants [6].

In 2004, the anticoagulant ximelagatran [7] was the first drug to try to substitute warfarin in non-valvular AF, but it was withdrawn from the market for hepatic toxicity. After that, three new drugs have been approved in this context, dabigatran [8], rivaroxaban, and apixaban [9]. The new oral anticoagulants have a shorter half-life, more predictable anticoagulant effect, lower propensity for food and drug interactions, and a more rapid offset of action than warfarin [5]. None of these drugs is recommended as first choice for patients with intraventricular thrombus, or for Chagas disease, due to lack of evidence.

Warfarin is recommended for stroke prevention in patients with intraventricular thrombus. For Chagas disease, the presence of left ventricular dysfunction and apical aneurysm is enough to recommend warfarin, even in the absence of thrombus [3], [10].

Benznidazole and nifurtimox are currently used for treatment of Chagas disease during the acute phase, reactivation, or congenital transmission. They may be used during the indeterminate phase and are contraindicated in the chronic phase with left ventricular dysfunction. On the other hand, the use of warfarin and/or new oral anticoagulants (NOAC) is indicated when left ventricular dysfunction and ventricular aneurism are present. The concomitant use of benznidazole or nifurtimox with warfarin or NOAC is not common. Rivaroxaban is metabolized by CYP3A4, benznidazole is mainly metabolized by other pathways, and CYP2C19 and nifurtimox are metabolized by cytochrome P450 reductase, so there is low risk of interaction between these drugs leading to increased bleeding events.

In this particular case we used rivaroxaban, beyond Chagas disease, because the patient had coronary artery disease and history of deep venous thrombosis. Moreover, the patient refused warfarin and he had had 2 embolic events in 5 months.

At the time of this event, the Aristotele trial was still ongoing and apixaban was not approved for regular use. In sub-groups of Re-ly [8], dabigatran was linked to a greater incidence of acute coronary syndrome. Rivaroxaban is a once-daily pill that makes it easier for patients who need many other medications and there is no higher incidence of myocardial infarction.

We prioritized patient adherence, safe use, and comorbidities such as coronary artery disease and deep venous thrombosis. The medical literature does not support the use of NOAC in ventricular thrombus for lack of evidence. We cannot say that the dissolution of the thrombi is a class effect. We recommend randomized trials to figure this out.

In this case, the use of rivaroxaban as secondary prevention in a chagasic patient with AF and a ventricular thrombus was not only effective but also decisive in the treatment of the intraventricular thrombus. After 20 months of regular use of rivaroxaban the patient had no more embolic events. The patient was submitted to a new echocardiography on July 2014, and no intraventricular thrombus was observed. These data suggest that rivaroxaban is a good alternative to warfarin to treat intraventricular thrombus.

Limitations

The limited experience of just one case does not allow any definitive conclusions in this respect.

Conflict of interest

The authors declare no conflict of interest.