SUMMARY

• XARELTO is not indicated for the treatment of cardiomyopathy.
• A retrospective study compared the effectiveness and safety of nonvitamin K antagonist oral anticoagulants (NOACs, including XARELTO and dabigatran) vs warfarin in patients with hypertrophic cardiomyopathy and nonvalvular atrial fibrillation (NVAF). The results showed that the NOAC-treated patients had a significant reduction in the risk of clinically relevant bleeding (P=0.011) and gastrointestinal bleeding (P=0.032) compared with warfarintreated patients. In a Kaplan-Meier analysis, the incidence of all-cause death (log-rank P=0.239), cardiovascular death (log-rank P=0.386), and thromboembolic events (log-rank P=0.257) was comparable between the 2 treatment groups.¹
• A cohort study compared the efficacy and safety of direct oral anticoagulants (DOACs, including XARELTO and dabigatran) vs warfarin in patients with dilated cardiomyopathy and left ventricular (LV) thrombus. The results showed no significant differences in terms of LV thrombus evolution between DOACs and warfarin; the risk of stroke and systemic embolism (SSE) was similar between the 2 treatment groups (odds ratio [OR], 0.904; 95% confidence interval [CI], 0.145-5.635).²
• Case reports describing the off-label use of XARELTO in patients with cardiomyopathy have been summarized below.^3-8
• Additional citations are included in the REFERENCES section for your review.^9-12

REAL-WORLD STUDIES

Lin et al (2022)¹ conducted a single-center, retrospective study that compared the effectiveness and safety of NOACs, including XARELTO and dabigatran vs warfarin in patients with hypertrophic cardiomyopathy and NVAF from January 2015 to December 2019.

• Of the 124 patients, 76 (61.3%) received NOACs (XARELTO, n=42 [55.3%]; dabigatran, n=34 [44.7%]) and 48 (38.7%) received warfarin.
  • In the NOAC and warfarin groups, respectively, 48 (63.2%) and 28 (58.3%) patients were >65 years old and 31 (40.8%) and 17 (35.4%) patients were male.
  • The average follow-up time, from the start of anticoagulation treatment to the final followup interview, was 53.6±2.0 months (NOACs, 55.0±2.6 months; warfarin, 51.1±3.2 months).
• In a Kaplan-Meier (KM) analysis, the incidence of clinically relevant bleeding was significantly lower in patients treated with NOACs vs warfarin (log-rank P=0.039). The incidence of all-cause death (log-rank P=0.239), cardiovascular death (log-rank P=0.386), and thromboembolic events (log-rank P=0.257) was comparable between the 2 treatment groups.
• NOAC-treated patients showed a significant reduction in the risk of clinically relevant bleeding (P=0.011) and gastrointestinal bleeding (P=0.032) compared with warfarintreated patients. Data regarding the long-term clinical outcomes in NOAC- and warfarin-treated patients are summarized in Table: Longterm Clinical Outcomes With NOACs vs Warfarin in Patients With Hypertrophic Cardiomyopathy and NVAF.
  • No statistically significant differences were observed between XARELTO and dabigatran in terms of all-cause death, cardiovascular death, thromboembolic events, or clinically relevant bleeding.
  • Overall, 2 deaths from cardiovascular causes and 1 death from non-cardiovascular causes were reported among the XARELTO-treated patients, whereas 4 deaths from cardiovascular causes were reported among the dabigatran-treated patients.

Huang et al (2023)² conducted a cohort study that compared the efficacy and safety of DOACs, including XARELTO and dabigatran vs warfarin in patients with dilated cardiomyopathy and LV thrombus, admitted at Fuwai Hospital, Beijing, China, from June 2011 to February 2023.

• Of the 112 patients prescribed oral anticoagulation, 47 (42.0%) received DOACs (XARELTO, n=42 [89.4%]; dabigatran, n=5 [10.6%]) and 65 (58.0%) received warfarin.
  • In the DOAC and warfarin groups, mean (standard deviation [SD]) age was 43.83 (13.29) and 38.88 (12.99) years, respectively. In the 2 groups, 38 (80.9%) and 53 (81.5%) patients were male, respectively.
  • The median (interquartile range [IQR]) follow-up duration was 12.5 (3.6-40.9) months.
• Among the 122 patients included, all-cause death, heart failure (HF) rehospitalization, SSE, and major adverse cardiovascular events (MACE) occurred in 34 (27.9%), 17 (13.9%), 5 (4.1%), and 52 (42.6%) patients, respectively, during the follow-up period.
• There were no significant differences in terms of LV thrombus evolution between DOACs and warfarin; the risk of SSE was comparable between the 2 treatment groups (OR, 0.904; 95% CI, 0.145-5.635).
• Data regarding thrombus evolution in patients treated with DOACs vs warfarin are summarized in Table: Thrombus Evolution in Patients Treated With DOACs vs Warfarin.

CASE REPORTS

Degheim et al (2017)³ reported the case of a 57-year-old male with a history of nonischemic cardiomyopathy, paroxysmal atrial fibrillation (PAF), hypertension, diabetes mellitus and compliant with all medications including XARELTO for PAF. Upon arrival at the emergency department, the patient complained of worsening lower extremity edema and dyspnea on exertion. The examination revealed tachycardia, irregularly irregular rhythm, systolic murmur, diffuse rales bilaterally on lung exam, and 2+ pitting edema of lower extremities. An electrocardiogram (ECG) showed atrial fibrillation with a ventricular rate of 120 beats per minute. An echocardiogram was performed and showed a LV apical thrombus, moderate tricuspid regurgitation, and a severely reduced LV systolic function (estimated ejection fraction [EF] of 10-15%). Patient’s XARELTO was discontinued, and heparin infusion was initiated due to magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) findings of a subacute nonhemorrhagic infarct of the left parietal lobe. Heparin infusion was transitioned to warfarin with a target International Normalized Ratio (INR) of 2-3. The patient was later transferred to a rehabilitation floor and eventually discharged home.

Sun et al (2018)⁴ reported the case of a 43-year-old Asian male who in the Cardiology department was found to have a left ventricle mass and felt dizzy at rest. The patient was admitted to the hospital where an echocardiography found a thrombosis like mass in the left ventricle and was confirmed by cardiac acoustic contrast. Patient had an EF that was as low as 43%. XARELTO 10 mg once daily was prescribed due to patient’s reluctance to repeated blood test and bleeding risk with warfarin treatment.  Follow-up after 15 days, 45 days and 3 months showed thrombus size had decreased and at the 3-month follow-up had vanished. An echocardiographic assessment was done and revealed a suspected left ventricular noncompaction cardiomyopathy. The patient also had a cardiac magnetic resonance exam which found hyper-trabeculation of the myocardium at apex and free wall confirming a diagnosis of left ventricular non-compaction cardiomyopathy (LVNC). Additional monitoring suggested nonsustained ventricular tachycardia and the patient was given XARELTO 10 mg once daily and a beta-blocker.

Umeojiako et al (2018)⁵ reported the case of a British women aged 83 years with a history of permanent AF, hypertension, and prior stroke (10 days earlier). In the emergency department, the patient reported 2 days of exertional dyspnea and chest tightness. She underwent several tests: ECG, chest X-ray, echocardiogram, contrast echocardiogram, coronary angiogram, cardiovascular MRI, and blood tests. The ECG showed LV hypertrophy in addition to AF. Echocardiograms appeared to show normal LV systolic function, biplane EF of 59% without contrast and 61% with contrast and marked hypertrophy of the mid to apical LV which appeared consistent with apical hypertrophic cardiomyopathy. The cardiovascular MRI also suggested apical hypertrophic cardiomyopathy. The patient was referred to the cardiomyopathy outpatient clinic and discharged on XARELTO, bisoprolol, and atorvastatin.

Aydin et al (2018)⁶ reported the case of a male patient aged 67 years with coronary artery disease, AF, hypertension, heart failure (HF; EF=35%), ischemic dilated cardiomyopathy, and a history of myocardial infarction. The patient was being treated with warfarin but was switched to XARELTO 20 mg once daily due to INR fluctuations upon diagnosis of a fixed thrombus via transthoracic echocardiography once admitted to the clinic. The thrombus regressed after 6 months of XARELTO use. XARELTO was then continued since there was no increase in size of the thrombus and no bleeding or thromboembolic event.

Fonseca et al (2021)⁷ reported the case of a 40-year-old male who presented with a 7day history of progressive breathlessness, orthopnea, and peripheral edema. ECG revealed a left bundle branch block. Transthoracic echocardiography revealed severe biventricular dysfunction associated with a ‘cystic’ LV mass. There was no evidence of pulmonary or systemic embolism. The patient was started on warfarin for suspected thrombus along with bridging low molecular weight heparin (LMWH). Cardiovascular magnetic resonance (CMR) imaging revealed severe biventricular dilatation and dysfunction (EF ~20%) with hypertrabeculation in the range of noncompaction. Early and late gadolinium imaging confirmed the presence of multiple LV thrombi, right ventricular thrombi, and extensive subepicardial late gadolinium enhancement. The patient was discharged on warfarin and guideline-based HF medication. Off-label XARELTO was initiated after 8 months of poor INR control due to erratic compliance. CMR repeated after 1 year showed complete resolution of thrombi despite persistent severe LV dysfunction.

Sisakian et al (2021)⁸ reported the case of a 25-year-old female who complained of dyspnea and fatigue 3 months postpartum. The patient was diagnosed with peripartum cardiomyopathy (PPCM) and received HF treatment that included low doses of metoprolol succinate (25 mg daily) and zofenopril (15 mg daily) to maintain stable hemodynamics, a low dose of ivabradine (5 mg daily) to control heart rate, spironolactone, and furosemide. Additionally, the patient received bromocriptine (2.5 mg twice daily) along with XARELTO (20 mg daily) for 3 months to prevent thromboembolic complications. After 2 years of follow-up, ECG revealed an increase in left ventricular ejection fraction (LVEF) from 25% to 35% and a decrease in LV end-diastolic diameter (LVEDD) from 5.8 cm to 5.2 cm. Additionally, speckle tracking echocardiography (STE) displayed a noticeable improvement in the LV global longitudinal strain (GLS) from -7.3% to -14%.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, Derwent^® (and/or other resources, including internal/external databases) was conducted on 02 July 2024.