Efficacy of Direct Acting Oral Anticoagulants in Treatment of Left Ventricular Thrombus

Design

Retrospective chart review

N= 52

Objective

To determine the efficacy and safety of DOACs in treatment of LV thrombus utilizing transthoracic echocardiography (TTE) and clinical outcomes

Study Groups

Apixaban (n= 26)

Rivaroxaban (n= 24)

Dabigatran (n= 2)

Inclusion criteria

Patients with discrete, measurable LV thrombus; treated with a DOAC

Exclusion criteria

On anticoagulation when LV thrombus was diagnosed

Methods

This was a single-center, retrospective study from an institute in Missouri. One cardiologist reviewed initial and follow-up TEEs in a random and blinded fashion to confirm the presence or absence of LV thrombus.

Duration

October 2010 to October 2018

Outcome Measures

Baseline Characteristics

There were 32 males (61.5%) and the mean age of all patients was 64 years. Eight patients (15.3%) were not on antiplatelet therapy and the mean baseline ejection fraction was 31%. Thirty-five patients (67%) had a follow-up TTE.

Results

Of the 35 patients with follow-up TTE, 29 (82.9%) had a complete resolution of LV thrombus. The mean time to resolution was 264 days. 

Of the 17 patients who had no follow-up TTE, three reported death and one had GI bleed. The others were lost to follow-up.

Adverse Events

One of the 52 patients (2%) had a cardioembolic event (transient ischemic attack) that occurred after 52 days of DOAC use.

Three of the 52 patients (6%) had GI bleed requiring transfusion, and one patient (2%) had epistasis requiring transfusion.

Study Author Conclusions

Direct oral anticoagulation (DOAC) therapy appears promising for the treatment of LV thrombus, but a larger, prospective study is warranted to confirm these results

InpharmD Researcher Critique

This was a retrospective review from a single center in Kansas City. There was little reported about the choice of DOAC, which can be presumed to be physician discretion. There was no comparison between the DOACs or warfarin therapy. Additionally, no statistical analysis was conducted at all in this cohort.

Apixaban vs. warfarin in patients with left ventricular thrombus: a prospective multicentre randomized clinical trial

Design

Prospective, open-label, multicenter, randomized clinical trial

N= 35

Objective

To assess the efficacy of apixaban vs. warfarin in treating left ventricular (LV) thrombus after myocardial infarction (MI)

Study Groups

Apixaban (n= 18)

Warfarin (n= 17)

Inclusion Criteria

Patients who showed evidence of LV thrombus assessed by 2D transthoracic echocardiography (2D-TTE) 1 to 14 days following acute MI

Exclusion Criteria

Contraindications for chronic anticoagulation, severe renal failure defined as creatinine clearance (CrCl) < 15 mL/min, patients with other indications for chronic anticoagulation (e.g. atrial fibrillation, pulmonary embolism), patients with technically limited 2D-TEE

Methods

Patients were randomized to either treatment with oral apixaban 5 mg twice daily or subcutaneous enoxaparin 1 mg/kg twice daily followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0–3.0 for 3 months. Patients in the apixaban group were assessed by phone contact on a weekly basis for compliance and medication adherence.

Apixaban doses were adjusted to 2.5 mg twice daily in patients with two or more of the following criteria: age of at least 80 years; body weight of no more than 60 kg; serum creatinine level of 1.5 mg/dL (133 μmol/L) or higher. Patients with advanced renal failure (CrCl between 15 and 29 mL/min) also received the adjusted dose.

Patients in the warfarin group had INR monitored, with dosing adjusted to achieve INR between 2 and 3. Time in therapeutic range (TTR) was documented for each patient.

All other medications including antiplatelet drugs were given at the discretion of the treating physician and according to the local policy of each center. All patients were followed at 1 and 3 months for recording of adverse events.

Assuming a thrombus resolution rate of 95% in each treatment group, the study determined that a sample size of 34 patients (17 in each group) would provide a statistical power of at least 80% with an absolute non-inferiority margin of 20%, and an alpha level of 0.05, to show the non-inferiority of apixaban therapy compared to warfarin. 

Duration

January 1, 2018 to September 30, 2020

Outcome Measures

Primary: Complete resolution of thrombus as assessed by 2D-TTE after 3 months of treatment

Secondary: major bleeding, stroke or systemic embolism, re-hospitalization for cardiovascular reasons and for noncardiovascular reasons, death from any cause up to 3 months

Baseline Characteristics

Apixaban (n= 18)

Warfarin (n= 17)

Age, years

Male

Hypertension

Dyslipidemia 

Current smokers

Diabetes mellitus 

Obesity (BMI > 30 kg/m²)

Prior IHD

Prior CKD

Baseline EF, %

Baseline thrombus length, mm

Baseline thrombus width, mm

35 ± 5

19.9 ± 9.4

12.4 ± 5.8

36 ± 7

18.5 ± 6.9

12.3 ± 4

Abbreviations: BMI, body mass index; CKD, chronic kidney disease (glomerular filtration rate <50 mL/min); EF, ejection fraction; IHD, ischemic heart disease

Results

Endpoint

Apixaban (n= 17)

Warfarin (n= 15)

p-value

Complete resolution of thrombus after 3 months of treatment

1 (superiority);
0.026 (non-inferiority)

Change in EF from baseline, %

0.17

Major bleeding 

Stroke/embolic event 

All-cause mortality 

Cardiovascular event^a

Other events^b

All events 

^aHospitalization due to MI, congestive heart failure, or arrhythmias 

^bHospitalization for non-cardiovascular events 

Missing p-values were due to the study not being powered to assess these events.

Sensitivity analyses were performed assuming those who lost to follow-up or died had events or only those in the apixaban group had an event. These yielded similar results.

One patient in the apixaban group, a 79-year-old female, after late arrival anterior MI died suddenly at home 68 days after the MI.

Adverse Events

See results

Study Author Conclusions

This study suggests that apixaban is an effective treatment for LV thrombus in patients after MI and may be considered in these high-risk patients; larger studies are still needed to reach more definitive conclusions.

InpharmD Researcher Critique

Comparative Effectiveness of Direct Oral Anticoagulants and Warfarin for the Treatment of Left Ventricular Thrombus

Design

Retrospective chart review

N= 949

Objective

To observe the use of direct oral anticoagulants (DOACs) for left ventricular (LV) thrombus

Study Groups

DOAC (n= 180)

VKA (n= 769)

Inclusion criteria

Diagnosis of LV thrombus, received either a DOAC or warfarin within 90 days of diagnosis

Methods

This was a retrospective review of a university hospital system in Colorado. There was no information on methodology of diagnosis or time on treatment.

Duration

September 2012 to October 2018

Outcome Measures

Baseline Characteristics

DOAC (n= 180)

VKA (n= 769)

Age, years

Male

Concurrent antiplatelets

Comorbidities

Atrial fibrillation

Myocardial infarction

111 (61.7%)

77 (42.8%)

325 (45.8%)

443 (57.6%)

Of the DOAC cohort, 75 (41.6%) received rivaroxaban, 77 (42.7%) apixaban, and 28 (15.7%) dabigatran.

Results

DOAC (n= 180)

VKA (n= 769)

p-value

New thromboembolic stroke within 90 days

Composite incidence of thromboembolic events

Bleeding events

Adverse Events

Study Author Conclusions

Compared to warfarin, DOACs may be safe and efficacious for the treatment of LV thrombus.

InpharmD Researcher Critique

This study was presented as a poster, so many of the methods were not presented. 

Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi

Design

Retrospective chart review

N= 514

Objective

To compare the outcomes associated with direct oral anticoagulant (DOAC) use and warfarin use for the treatment of left ventricular (LV) thrombi

Study Groups

DOAC only (n= 121)

Warfarin only (n= 236)

Therapy change (n= 64)

Neither (n= 93)

Inclusion criteria

Patients with echocardiographically diagnosed LV thrombi

Exclusion criteria

None reported

Methods

The treatment patterns of patients with LV thrombi were retrospectively examined from thee tertiary care academic medical centers. Treatments consisted of warfarin only, DOAC only, therapy change (either warfarin to or from DOAC), or other anticoagulation (e.g. parenteral anticoagulation).

Patients who had not already experienced a stroke or systemic embolism (SSE) or censoring event (death, heart transplant, surgical LV assist device placement, or surgical thrombectomy) by medical record review were individually contacted by telephone for a final ascertainment of events.

Duration

October 2013 to March 2019

Median follow-up duration: 351 days

Outcome Measures

Baseline Characteristics

DOAC only (n= 121)

Warfarin only (n= 236)

Therapy change (n= 64)

Neither (n= 93)

Age, years

Male

White race

LVEF, %

Thrombus size, cm²

Antiplatelet therapy

LVEF=left ventricular ejection fraction

Of the 185 patients who received any DOAC, 141 (76.2%) received apixaban, 46 (24.9%) received rivaroxaban, and 9 (4.9%) received dabigatran. This includes a mixed cohort of patients who may have received multiple DOACs.

Results

DOAC use

Warfarin use

Parenteral anticoagulation

No anticoagulation

SSE

Death

Bleeding

Imaging surveillance was variable, with 356 patients (69.3%) having at least 1 follow-up echocardiogram. A total of 231 patients had echocardiographically confirmed resolution of their thrombus, including 56 while being treated with a DOAC, 131 while being treated with warfarin, 21 during treatment with parenteral anticoagulation, and 23 without any anticoagulation. 

On univariable Cox proportional hazards regression analysis, a higher risk of SSE was significantly associated with DOAC use vs warfarin (hazard ratio [HR] 2.71; 95% confidence interval [CI] 1.31 to 5.57; P=0.01).

Prior SSE was also a significant risk factor for future SSE on the univariate analysis (HR 2.13; 95% CI 1.22 to 3.72; P=0.01).

Adverse Events

Study Author Conclusions

In this multicenter cohort study of anticoagulation strategies for LV thrombi, DOAC treatment was associated with a higher risk of stroke or systemic embolism (SSE) compared with warfarin use, even after adjustment for other factors. These results challenge the assumption of DOAC equivalence with warfarin for LV thrombi and highlight the need for prospective randomized clinical trials to determine the most effective treatment strategies for LV thrombi.

InpharmD Researcher Critique

This study is limited but the retrospective design, which allows for confounding variables that were not accounted for. No centralized review of echocardiographic images was conducted; instead, the authors relied on clinical reports of each echocardiogram and the local measurement of the 2-dimensional thrombus area. Dosing adherence and target INR (for warfarin) were not reported.

This study conducted multiple analyses including univariate and multivariate analyses on the different treatments given, which leads to a higher probability of finding a statistically significant result. A Bonferroni correction should have been used due to the multiple comparisons and several statistical tests being performed simultaneously.

Management of Left Ventricular Thrombi with Direct Oral Anticoagulants: Retrospective Comparative Study with Vitamin K Antagonists

Design

Retrospective chart review

N= 59

Objective

To compare the efficacy of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) in patients with left ventricular (LV) thrombi and evaluate the rate of LV thrombus resolution after adjusting anticoagulation

Study Groups

DOAC (n= 17)

VKA (n= 42)

Methods

Inclusion criteria: consecutive patients with LV thrombus detected via transthoracic echocardiography (TEE) at a single center

Exclusion criteria: none described

All patients with LV thrombus were put on anticoagulants (including DOACs and VKAs [INR 2-3]) for at least 3 months per practitioner preference. Upon evaluation, patients without thrombus resolution with DOACs were switched to VKA therapy (INR 3-4).

Duration

January 2010 to August 2019

Outcome Measures

Baseline Characteristics

DOACs (n= 17)

VKA (n= 42)

Age, years

Female

Left ventricular ejection fraction, %

Comorbidities

Hypertension

Hyperlipidemia

Structural heart disease

Ischemic cardiomyopathy

10 (59%)

5 (29%)

17 (100%)

15 (88%)

17 (41%)

18 (43%)

42 (100%)

35 (74%)

Results

Complete thrombus resolution at 3 months

DOACs (n=17)

Rivaroxaban (n=4)

Apixaban (n=12)

Dabigatran (n=1)

12/17 (71%)

1 (25%)

11 (92%)

0

VKAs (n=42)

Acenocoumarol (n=12)

Fluindione (n=16)

Warfarin (n=14)

30 (72%)

10 (83%)

13 (82%)

7 (50%)

The five patients who failed DOAC therapy were switched to VKA therapy [goal INR 3-4]. All of these patients resulted in dissolved LV thrombus.

The DOACs showed similar efficacy for dissolving LV thrombi as VKAs (70.6% vs. 71.5%; P=0.9). The risk of embolic events appeared to be similar with DOACs to that of the VKAs used (11.8% vs. 9.5%; P=0.8).

Adverse Events

Study Author Conclusions

This retrospective observational study found a similar efcacy between DOAC and VKA agents in patients with LV thrombi (70.6% vs. 71.5%); however, when the thrombus remains, VKAs are still the standard of care as it is possible to control INR levels (3–4) with them.

InpharmD Researcher Critique

This was a retrospective study from a single center in France. The study’s statistical power was also low given the number of LV thrombi identified and the groups were not even due to prescriber preference and practice changes over the study duration (2010 to 2019). Thrombus detection was conducted via TEE instead of MRI.

Apixaban versus Warfarin in Patients with Left Ventricular Thrombus: A Pilot Prospective Randomized Outcome Blinded Study Investigating Size Reduction or Resolution of Left Ventricular Thrombus

Design

Prospective, single-center, randomized, single-blinded pilot study

N= 27

Objective

To conduct a pilot prospective randomized single-blinded outcome study investigating the size reduction or resolution of left ventricular thrombus (LVT) with apixaban compared to conventional warfarin

Study Groups

Apixaban (n= 14)

Warfarin (n= 13)

Inclusion Criteria

Aged 18-80 years old; heart failure diagnosis with newly discovered LVT; HAS-BLED score of <3

Exclusion Criteria

Major bleeding in the past 6 months; history of intracranial bleeding or large ischemic stroke; advanced renal and liver disease on cardiac devices; clinically unstable or in shock

Methods

Patients were allocated to apixaban 5 mg twice daily for 12 weeks (or 2.5 mg twice daily should renal dose adjustment requirements be met) or standard therapy of warfarin with initial heparin infusion, aiming for a target INR of 2-3. Postangioplasty patients were placed on triple therapy (apixaban/warfarin + dual antiplatelet therapy). Echocardiographers were blinded to patient treatment; unblinding of the reports was conducted only when any suspected adverse events occurred.

Duration

Follow-up: up to 15 weeks

Outcome Measures

Baseline Characteristics

Apixaban (n= 14)

Warfarin (n= 13)

Age, years

Female

Comorbidities

Diabetes mellitus

Hypertension

Ischemic heart disease

Atrial fibrillation

Chronic kidney disease

Hyperlipidemia

7 (50.0%)

8 (57.1%)

9 (64.3%)

1 (7.1%)

5 (35.7%)

8 (57.1%)

9 (69.2%)

9 (69.2%)

8 (61.5%)

0

7 (53.8%)

9 (69.2%)

HAS-BLED score

Mean ejection fraction on echocardiography was 33.5%.

Results

Endpoint

Apixaban

Warfarin

Mean difference in LVT size, cm2 (95% CI); p-value

Week 0-6

Week 0-12

Week 6-12

1.98 (0.41 to 3.55); 0.013

2.40 (0.76 to 4.04); 0.005

0.42 (−0.19 to 1.03); 0.233

0.95 (0.17 to 1.73); 0.017

1.33 (0.22 to 2.43); 0.018

0.38 (−0.27 to 1.02); 0.380

Mean percentage reduction*

65.08% (n= 13)

61.45% (n= 11)

Endpoint

Overall LVT difference between groups 

Comparison of LVT differences based on time

Week 0

Week 6

Week 12

0.68 (−0.59 to 1.95)

−0.34 (−1.49 to 0.82)

−0.38 (−1.62 to 0.85)

0.278

0.550

0.529

Abbreviations: LVT, left ventricular thrombus; CI, confidence interval

* Mean difference for percentage reduction between-groups is −3.62 (95% CI −35.57 to 28.32); p-value= 0.816.

Adverse Events

Two patients died in the apixaban arm due to massive ischemic stroke with hemorrhagic transformation and worsening heart failure versus four patients dying in the warfarin arm (causes not mentioned).

Study Author Conclusions

This pilot study suggests that apixaban may have similar effectiveness and safety to warfarin for LVT resolution.

InpharmD Researcher Critique

Data from this study may be less generalizable to a larger patient population due to its open-label nature and limited sample size. Safety outcomes were reportedly similar; however, adverse events related to treatment drug were not discussed. Additionally, as the study was conducted outside of the U.S., results may not be extrapolatable to the domestic patient population.

Apixaban in Patients With Post-Myocardial Infarction Left Ventricular Thrombus: A Randomized Clinical Trial

Design

Prospective, open-label, randomized controlled trial

N= 50

Objective

To compare the efficacy and safety of apixaban with that of warfarin for the resolution of post-myocardial infarction (MI) left ventricle thrombus (LVT) in contemporary practice

Study Groups

Apixaban (n= 25)

Warfarin (n= 25)

Inclusion Criteria

Age ≥18 years, naïve to oral anticoagulant (OAC) therapy, with an acute (within 1 week) or recent (within a month) anterior wall MI, and evident LVT

Exclusion Criteria

Patients with OAC indications other than MI/LVT, history of confirmed stroke or systemic embolization within the last 6 months, high bleed risk (based on Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly (> 65 Years), Drugs/Alcohol Concomitantly [HASBLED] score ≥ 3), challenging echocardiogram with difficult assessment of LVT,  expected adherence issues

Methods

For apixaban to achieve noninferiority, it had to achieve ≥ 95% LVT resolution, compared with warfarin. Sample size was determined by contemporary practice. Two independent echocardiography experts analyzed each echocardiographic study. In cases of discordance regarding the existence of LVT at enrollment, the patient was not enrolled in the study. In cases of discordance regarding the resolution at follow-up, a third expert independently evaluated the echocardiographic study, and a consensus was reached to confirm the findings. LVT regression was defined as LVT area reduction of at least 25% reported by either or both experts. The experts reporting the echocardiographic studies were blinded to the treatment groups.

LVT was defined as an echo-dense mass distinct from the endocardium with well-defined edges adjacent to a hypokinetic, akinetic, or aneurysmal myocardial segment and had to be visible in at least 2 views during the cardiac cycle. Transthoracic echocardiogram (TTE) was performed without echo-contrast. The echocardiographic assessment included LV ejection fraction (LVEF), LV volume, apical wall motion score index (WMSI), and the identification of an apical aneurysm. Echocardiography was performed at baseline, and at 1, 3, and 6 months.

Patients were randomized 1:1 to apixaban 5 mg twice daily or dose-adjusted warfarin with a target INR of 2.0 to 3.0 for the study duration. At the discretion of the treating physician, the warfarin group may have been treated with therapeutic heparin (subcutaneous enoxaparin or intravenous heparin infusion if hospitalized) until a therapeutic INR was achieved. Both groups received triple therapy for at least 1 month, to a maximum of 3 months, unless the clinical condition or bleeding risk mandated the modification of this policy. Clopidogrel was used throughout the study; aspirin was resumed once LVT resolution was confirmed, and OAC was discontinued. All enrolled patients were prescribed oral proton pump inhibitors (PPI). The warfarin group was strictly followed by a dedicated anticoagulation clinic managed by a clinical pharmacist to ensure an INR between 2 and 3.

Duration

Enrollment: September 2018 to July 2021

Intervention: ≥1 month to ≤3 months

Follow-up: 6 months from randomization

Outcome Measures

Primary Outcome: complete LVT resolution after 3 months of treatment

Secondary Outcomes: LVT status at 6 months of treatment; composite major adverse cardiovascular events, defined as the composite of all-cause death, ischemic stroke or transient ischemic attack, MI or acute peripheral artery emboli, and any clinically relevant bleeding events (Bleeding Academic Research Consortium [BARC] score ≥ 2)

Baseline Characteristics

Apixaban (n= 25)

Warfarin (n=25)

Age, years

Weight, kg

BMI, kg/m²

Comorbid conditions

DM

HTN

Smoking

12 (48%)

11 (44%)

11 (44%)

11 (44%)

10 (40%)

12 (48%)

SCr, mg/dL

Hemoglobin level, gm/dL

HAS-BLED score

History of prior/old MI

Lytic use for AMI

Medication use

Aspirin

Clopidogrel

DAPT

Heparin/Enoxaparin ^b

20 (80%)

24 (96%)

20 (80%)

16 (64%)

20 (80%)

25 (100%)

20 (80%)

21 (84%)

Time from MI to echo, days

AMI

Recent MI

25 ±0.45

32 ±4.6

2.5 ±0.46

33 ±4.8

Hospital stay, days ^b

Number of study-related visits

3 months ^b

6 months ^b

2.4 ±0.10

3.64 ±0.14

7.4 ±0.25

9.2 ±0.24 

ECHO Characteristics

LVEDV, mL

LVESV, mL

LVEF, %

Apical WMSI

Apical aneurysm

LVT length, mm

LVT width, mm

LVT area, cm²

Mobile LVT

Fresh and/or Protruding LVT

171.5 ± 29.5

122.8 ± 32.1

26.4 ± 6.1

2.88 ± 0.25

14 (56%)

28.6 ± 9.6

15.4 ± 7.1

2.9 ± 1.3

12 (48%)

22 (88%)

170.2 ± 28.6

115.8 ± 31.2

27.3 ± 9.2

2.85 ± 0.39

13 (52%)

25.6 ± 11.5

15.9 ± 6.4

2.7 ± 1.2

11 (44%)

21 (84%)

Values are mean ± standard deviation or n (%), unless otherwise indicated.

AMI, acute myocardial infarction; BMI, body mass index; DAPT, dual antiplatelet therapy; DM, diabetes mellitus; HTN, hypertension; MI, myocardial infarction; PCI, percutaneous coronary intervention

LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; LVT, left ventricular thrombus; WMSI, wall motion score index

^a Index admission PCI: either PCI during the same admission as that of left ventricular thrombus diagnosis or primary PCI.

^b Were found to be statically different between treatment groups. Heparin/Enoxaparin use (p= 0.028); Hospital stay days (p= 0.042); Number of study related visits at 3 months (p= 0.036); 6 months (p= 0.024)

Results

Endpoints

Apixaban (n = 25)

Warfarin (n=25)

p-value

LV thrombus at 1 month

Persistent

Regression

Resolution

2 (8%)

13 (52%)

10 (40%)

1 (4%)

10 (40%)

14 (56%)

0.165

LV thrombus at 3 months

Persistent

Regression

Resolution

1 (4%)

5 (20%)

19 (76%)

0

5 (20%)

20 (80%)

0.303

LV thrombus at 6 months

Regression

Resolution

2 (8%)

23 (92%)

1 (4%)

24 (96%)

0.366

LVT regression = LVT area reduction of at least 25% reported by either or both echocardiographic experts;

LVT persistence = as increased thrombus dimension, stable thrombus size, or controversial minor thrombus regression at follow-up.

Adverse Events

Adverse Events: One patient in the warfarin group (on triple therapy) had a 2.3 gm/dL drop of hemoglobin at 1-month follow-up (BARC score: 2) with INR in acceptable range. Aspirin therapy was halted, PPI therapy was increased and hemoglobin improved during next visit.

Serious Adverse Events: None of the patients demonstrated stroke, transient ischemic attack, or other systemic embolisms, new MI, death from any cause, unscheduled hospitalization, or clinical evidence of bleeding during this period.

Percentage that Discontinued due to Adverse Events: All study patients completed up to 6 months of the initially allocated OAC medication.

Study Author Conclusions

In this prospective randomized, open-label controlled clinical trial, apixaban was not inferior to warfarin in terms of LVT resolution after acute or recent MI.

InpharmD Researcher Critique

Due to open labeling and a small sample size, interpretation of this study should be used with caution. The authors point out exclusion of 3 randomized patients  (5.4%) was performed due to protocol violations regarding consent. Additionally, generalization to older and sick patients is not advised by the authors due to power issues.

An exploratory study of effectiveness and safety of rivaroxaban in patients with left ventricular thrombus (R-DISSOLVE)

Design

Single-center, prospective, interventional, single-arm study (R-DISSOLVE); China 

N= 75

Objective

Study Groups

Inclusion Criteria

Adults; evidence of LV thrombus identified by either transthoracic echocardiography, computer tomography, or cardiac magnetic resonance imaging within 3 months; received systemic oral anticoagulation treatment for < 1 month

Exclusion Criteria

Contraindications to anticoagulation therapy; severe renal or liver dysfunction; history of hemorrhagic stroke or major bleeding within 1 month

Methods

Patients were assigned to rivaroxaban 20 mg once daily or 15 mg once daily if their creatinine clearance was 30–50 mL/min or if they were on dual antiplatelet therapy. Those on short-term anticoagulants were switched to rivaroxaban before or within 12 hours after baseline measurement. Adherence to treatment guidelines and avoidance of potent P-glycoprotein or cytochrome P3A4 inhibitors were emphasized. Rivaroxaban was promptly restarted after any invasive intervention.

Duration

October 2020 to June 2022

Follow up: 12 weeks 

Outcome Measures

Primary: Incidence rate of thrombus resolution at 12 weeks confirmed by contrast-enhanced imaging 

Secondary: Thrombus outcomes at 6-week and 12-week follow-ups

Baseline Characteristics

All patients (N= 75)

Age, years

Male

24.5 ± 3.1

Presenting diagnosis 

ICM

DCM

Other*

30 (40.0%)

29 (38.7%)

16 (21.3%)

Rivaroxaban dose

20 mg once daily

15 mg once daily**

42 (56.0%)

33 (44.0%)

Antiplatelet therapy 

10 (13.3%)

CrCl, mL/min

< 50

≥ 50 

10 (13.3%)

65 (86.7%)

Previous therapy

Oral anticoagulation therapy

Duration, days (IQR)

14 (18.7%)

5.5 (3-11)

Number of thrombi

1

≥ 2

48 (64.0%)

27 (36.0%)

Size of thrombi, mm (IQR)

Diameter

Thickness 

24.0 (17.5-35.5)

10.0 (7.0-13.5)

Abbreviations: IQR= interquartile range; BMI= body mass index; CrCl= creatinine clearance; DCM= dilated cardiomyopathy; ICM= ischemic cardiomyopathy

*Hypertensive heart disease (n= 5), inflammatory cardiomyopathy ( = 2), heart failure (n= 2), restrictive cardiomyopathy (n = 2), hypertrophic cardiomyopathy (n= 1, as follows), alcoholic cardiomyopathy, noncompaction of ventricular myocardium, chemotherapy-induced cardiomyopathy, and valvular heart disease

**Total of 31 (41.3%) patients received 15 mg, while 2 (2.7%) patients received 10 mg 

Results

Endpoint

All patients (N= 75)

95% confidence interval

Complete thrombus resolution at 12 weeks*

Resolved or reduced thrombus at 12 weeks*

Complete thrombus resolution at 6 weeks**

Resolved or reduced thrombus at 6 weeks**

Safety outcomes at 12 week follow up§

Major bleeding

Clinically relevant non-major bleeding

Stroke/embolism

All-cause death

Allergy causing rivaroxaban discontinuation

Rehospitalization†

2 (2.7%)

2 (2.7%)

3 (4.0%)

2 (2.7%)

1 (1.3%)

7 (9.3%)

-

-

-

-

-

-

*Total of 64 patients were analyzed 

**Total of 62 patients were analyzed

§Total of 75 patients were analyzed 

†Hospitalization due to congestive heart failure and arrhythmia

Adverse Events

Study Author Conclusions

InpharmD Researcher Critique

Comparative Study of Oral Anticoagulation in Left Ventricular Thrombi (No-LVT Trial)

Design

Letter to the editor for a prospective, open-label, multicenter, randomized clinical trial (Comparative Study of Oral Anticoagulation in Left Ventricular Thrombi [No-LVT]) 

N= 79

Objective

Study Groups

Rivaroxaban (n= 39) 

Warfarin (n= 40)

Inclusion Criteria

Aged ≥18 years; newly diagnosed LVT

Exclusion Criteria

Creatinine clearance <50 mL/min, history of atrial fibrillation, deep vein thrombosis/pulmonary embolism, and being on oral anticoagulation therapy for any other reason

Methods

Eligible patients were randomly assigned in a 1:1 ratio to either dose-adjusted warfarin or rivaroxaban 20 mg daily. Those assigned to the warfarin group were bridged via enoxaparin 1 mg/kg BID until reaching international normalized ratio of 2 to 3. Unblinded cardiologists interpreted all transthoracic echocardiography (TTE) studies at 1, 3, and 6 months to assess LVT over time. 

Duration

Follow-up: 6 months 

Outcome Measures

Primary: complete LVT resolution as assessed by TTE at 1, 3, and 6 months

Secondary: stroke, systemic embolism, and a composite of both

Safety: occurrence of major bleeding as defined according to the International Society of Thrombosis and Hemostasis criteria

Baseline Characteristics

Age, years

Female

Medical history

Hypertension

Diabetes mellitus 

Ischemic cardiomyopathy 

53.1%

53.1%

78.5% 

Mean left ventricular ejection fraction

Mean LVT size, mm

Dual antiplatelet therapy

Time in therapeutic range for the warfarin group

Overall, the 2 groups were balanced with respect to baseline characteristics and drug history.

Results

Endpoint

Rivaroxaban (n= 39)

Warfarin (n= 40)

p-value

Complete LVT resolution

1 month 

3 months 

6 months 

28 (71.79%)

30 (76.92%)

34 (87.17%)

19 (47.5%)

27 (67.5%)

32 (80%)

0.03

0.35

0.39

Secondary outcomes

Stroke 

Systemic embolic events

Composite 

0

0

0

4 (10%)

2 (5%)

6 (15%)

0.08

0.25

0.01

Major bleeding*

Generalized estimating equation for repeated measurement results showed that at 1 month, the odds ratio of LVT resolution in the rivaroxaban group was significantly higher than in the warfarin group (odds ratio 2.813; p= 0.03).

*75% of the bleeding events occurred in patients on dual antiplatelet therapy. 

Adverse Events

Study Author Conclusions

In conclusion, the No-LVT study is the first randomized controlled study to our knowledge to assess different oral anticoagulants in patients with LVT. Our results demonstrated that rivaroxaban was non-inferior and had faster thrombus resolution in comparison to warfarin.

InpharmD Researcher Critique

As the fully published article is unavailable, reported results are extrapolated from the letter to the editor and lack detailed information on baseline characteristics. The trial is conducted in 5 centers in Egypt and Bulgaria, limiting the external generalizability to the US population. The small sample size and low incidences of clinical thromboembolic events make it difficult to detect significant differences between the two groups.  

Use of dabigatran for treatment of left ventricular thrombus: A tertiary care center experience

Design

Single-center, retrospective, observational study

N= 15

Objective

To evaluate the effect of dabigatran in the treatment of left ventricular thrombus (LVT)

Study Groups

Inclusion Criteria

Consecutive patients who received dabigatran for treatment of LVT of any origin, not on any prior anticoagulation

Exclusion Criteria

Not explicitly stated

Methods

Patients were identified via retrospective review of medical records. Patients received dabigatran at a dose of 220 mg/day with antiplatelets or 300 mg/day without antiplatelets. Dabigatran was continued until 6 months even after clot resolution.

Duration

Data review: December 2016 to November 2018

Intervention: 6 months

Follow-up data: 6 months post-treatment initiation

Outcome Measures

Clinical outcomes during follow-up at 2 weeks, 1 month, 3 months, and 6 months post-dabigatran initiation

Baseline Characteristics

All patients (N= 15)

Age, years

Male

Left ventricular ejection fraction, %

Etiology

Ischemic cardiomyopathy

ST-elevation myocardial infarction

Nonischemic cardiomyopathy

Valvular heart disease

3 (20%)

7 (47%)

5 (33%)

0

Atrial fibrillation

Biventricular clot

LV thrombus size, cm²

Results

Endpoint

All patients (N= 15)

Follow-up at 2 weeks

Ejection fraction, %

Stroke

Distal embolization

Any bleeding

Complete clot resolution

50% clot resolution

Clot recurrence

New Clot

35 ± 6

0

0

0

5 (33%)

11 (73%)

0

0

Follow-up at 1 month

Ejection fraction, %

Stroke

Distal embolization

Any bleeding

Complete clot resolution

50% clot resolution

Clot recurrence

New Clot

36 ± 6

0

0

0

12 (80%)

15 (100%)

0

0

Follow-up at 3 months

Ejection fraction, %

Stroke

Distal embolization

Any bleeding

Complete clot resolution

50% clot resolution

Clot recurrence

New Clot

39 ± 7

0

0

1*

14 (93%)

15 (100%)

0

0

Follow-up at 6 months

Ejection fraction, %

Stroke

Distal embolization

Any bleeding

Complete clot resolution

50% clot resolution

Clot recurrence

New Clot

41 ± 7

0

0

0

15 (100%)

15 (100%)

0

0

Duration for complete clot resolution (IQR)

30 (14 to 30)

*Gastrointestinal bleeding

IQR, interquartile range

Adverse Events

See results.

Study Author Conclusions

Dabigatran appears to be safe, highly efficacious and results in rapid LV clot resolution. DOACs may be a suitable alternative to warfarin in treatment of LV thrombus. However, larger studies are required to validate this hypothesis.

InpharmD Researcher Critique

This study is limited by its small sample size and observational design. Additionally, formal statistical analyses were not conducted, nor was a control group utilized. Due to the likely presence of confounding variables, the results of this study should be interpreted with caution.