What literature and recommendations are available for the use of apixaban for left ventricular thrombus? What dose adjustments are recommended based on renal function?

Comment by InpharmD Researcher

Published literature of direct oral anticoagulants use, including apixaban, for left ventricular (LV) thrombus have consistently found DOAC use to be an effective treatment that may be considered in high-risk patients with a tolerable safety profile. Non-inferiority has been reported for apixaban therapy in comparison to warfarin in this patient population with regards to clinical outcomes (Table 3). Renal dosage adjustment for apixaban in the setting of LV thrombus is variable, and outcomes are limited to case reports (Table 8).
Background

The 2022 American Heart Association (AHA) statement on the management of patients with left ventricular (LV) thrombus notes that previous clinical guidelines lack discussion on the use of direct oral anticoagulants (DOACs), including apixaban, as an alternative to warfarin for the treatment of LV thrombus. Based on a meta-analysis of randomized controlled trials that evaluate outcomes of stroke and systemic thromboembolism in this patient population, DOACs may be considered a reasonable alternative to vitamin K antagonists (VKAs) in patients with LV thrombus, especially in patients who are unable to achieve therapeutic INR or who are unable to follow-up frequently for INR checks (e.g., lack of transportation). At the time of publishing, the panel did not find data on DOAC use for prophylaxis or treatment of LV thrombus in patients with end-stage renal disease (ESRD), and thus agent selection should be based on shared decision-making and individual clinical factors. [1]

Reviews describe that DOACs have an established place in therapy compared to warfarin for atrial fibrillation due to their favorable dosing scheme and lower bleeding risk. Since there are similarities between the pathophysiology of LV thrombus and atrial fibrillation-related cardiac thrombosis, recent literature has emerged supporting the use of DOACs as an alternative to warfarin for LV thrombus. A meta-analysis examining case reports of DOAC use for LV thrombus found a treatment success rate of 81% (17/21), 100% (8/8), and 88.9% (8/9) for rivaroxaban, apixaban, and dabigatran, respectively. The median time of thrombus resolution was 40 days, 36 days, and 24 days for rivaroxaban, apixaban, and dabigatran, respectively. Only one bleeding event was seen in a patient taking rivaroxaban, which ended in early termination of the medication. Available reports of apixaban therapy for LV thrombus have observed varied dosing regimens (see Table 1). [2], [3]

A 2021 meta-analysis included studies (N= 8) comparing the efficacy and safety of DOACs with oral VKAs in patients with LV thrombus, specifically stroke or systemic embolism (SSE), There was no significant difference in SSE resolution (odds ratio [OR] 0.89; 95% confidence interval [CI] 0.46 to 1.71; p= 0.73) or LV thrombus resolution (OR 1.13; 95% CI 0.75 to 1.71; p= 0.56) between DOAC and VKA therapy. However, there was a statistically significant association between utilizing DOAC and lower bleeding events incidence versus VKA use (OR 0.61; 95% CI 0.40 to 0.93; p= 0.02). Despite the observational design of the studies, relatively modest number of outcome events, and wide CIs which increase the risk of type II error, the authors concluded that DOAC utilization in LV thrombus treatment appears to be a reasonable alternative compared to VKAs use. Evaluation of DOAC dose and duration of treatment for LV thrombus was not within the scope of this analysis, and it was noted that it remains unclear which DOAC dose is the most appropriate for LV thrombus anticoagulation (i.e., DOAC doses approved for atrial fibrillation or doses for venous thromboembolism and whether initial overlap with parenteral anticoagulation is necessary). [4]

A 2018 Polish case series discussed the use of apixaban in the management of LV thrombi in seven patients, of which six had chronic kidney disease (CKD). Three patients had more than one LV thrombus, while three patients had other intracoronary thrombi (ICT) reported in the right ventricle and in the left atrial appendage. Three patients utilized apixaban doses of 5 mg twice daily, two patients used 2.5 mg twice a day, and two patients were administered increasing doses of apixaban. In all patients, gradual diminishing of LV thrombi was observed between 7 and 28 days (mean of 17 days), with no complications attributed to apixaban therapy. As access to the full article and its discussion on rationale behind selection of dosages is unavailable, these results should be regarded with caution. [5]

References:

[1] Levine GN, McEvoy JW, Fang JC, et al. Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association. Circulation. 2022;146(15):e205-e223. doi:10.1161/CIR.0000000000001092
[2] Kajy M, Shokr M, Ramappa P. Use of Direct Oral Anticoagulants in the Treatment of Left Ventricular Thrombus: Systematic Review of Current Literature. Am J Ther. 2020;27(6):e584-e590. doi:10.1097/MJT.0000000000000937
[3] Honan KA, Jogimahanti A, Khair T. An Updated Review of the Efficacy and Safety of Direct Oral Anticoagulants in Treatment of Left Ventricular Thrombus. Am J Med. 2022;135(1):17-23. doi:10.1016/j.amjmed.2021.07.023
[4] Kido K, Ghaffar YA, Lee JC, et al. Meta-analysis comparing direct oral anticoagulants versus vitamin K antagonists in patients with left ventricular thrombus. PLoS One. 2021;16(6):e0252549. Published 2021 Jun 4. doi:10.1371/journal.pone.0252549
[5] Elikowski W, Małek-Elikowska M, Wróblewski D, et al. Apixaban in left ventricular thrombi treatment - a report of seven cases. Pol Merkur Lekarski. 2018;44(264):276-279.
Relevant Prescribing Information

8.6 Renal Impairment [6]

The recommended dose is 2.5 mg twice daily in patients with at least two of the following characteristics:
Age greater than or equal to 80 years
Body weight less than or equal to 60 kg
Serum creatinine greater than or equal to 1.5 mg/dL

Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery, and Treatment of DVT and PE and Reduction in the Risk of Recurrence of DVT and PE
No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis. Clinical efficacy and safety studies with ELIQUIS did not enroll patients with ESRD on dialysis or patients with a CrCl <15 mL/min; therefore, dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in subjects with ESRD maintained on dialysis.

References:

[6] Eliquis (apixaban tablet). Prescribing information. E.R. Squibb & Sons, L.L.C.; 2021.
Literature Review

A search of the published medical literature revealed 8 studies investigating the researchable question:

What literature and recommendations are available for the use of apixaban for left ventricular thrombus? What dose adjustments are recommended based on renal function?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-8 for your response.

A summary of evidence for apixaban in treatment of LV thrombus
Author(s) Study Population Dose Study Findings
Bennett et al. 42-year-old male with a PMHx of hepatic dysfunction and transaminitis Unknown apixaban dose Complete dissolution of a 3.0 cm x 1.6 cm thrombus after only 6 days
Kaya et al. 60-year-old woman with a PMHx of hypertrophic cardiomyopathy Apixaban 5 mg every 12 hours Complete dissolution of a 3.03 cm x 1.96cm thrombus after 30 days

Abbreviations: PMHx, past medical history; LV, left ventricular
References:

Adapted from:
Honan KA, Jogimahanti A, Khair T. An Updated Review of the Efficacy and Safety of Direct Oral Anticoagulants in Treatment of Left Ventricular Thrombus. Am J Med. 2022;135(1):17-23. doi:10.1016/j.amjmed.2021.07.023

 

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

 Resolution of thrombus, time to thrombus resolution, adverse events

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.
References:

Fleddermann AM, Hayes CH, Magalski A, Main ML. Efficacy of Direct Acting Oral Anticoagulants in Treatment of Left Ventricular Thrombus. Am J Cardiol. 2019;124(3):367-372. doi:10.1016/j.amjcard.2019.05.009

 

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

 55.5 ± 12.9 58.8 ± 10.2  

Male

 13 (72.2%) 15 (88.2%)  

Hypertension

 7 (38.9%) 7 (41.2%)  

Dyslipidemia 

 7 (38.9%) 9 (52.9%)  

Current smokers

 13 (72.2%) 10 (58.8%)  

Diabetes mellitus 

 8 (44.4%) 5 (29.4%)  

Obesity (BMI > 30 kg/m2)

 4 (22.2%) 4 (23.5%)  

Prior IHD

 4 (22.2%) 3 (17.7%)  

Prior CKD

 3 (16.7%) 1 (5.9%)  

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

 16 (94.1%) 14 (93.3%)

1 (superiority);
0.026 (non-inferiority)

Change in EF from baseline, %

 5 ± 9 1 ± 2

0.17

Major bleeding 

 0  2   --

Stroke/embolic event 

 0  1  --

All-cause mortality 

 1  0  --

Cardiovascular eventa

 3 2 --

Other eventsb

 3 1  --

All events 

 7 (38.8%) 6 (40%) 0.8

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

 There were a few limitations including a relatively small sample size, the use of a large non-inferiority margin, and a lack of sufficient statistical power to assess clinical endpoints. Additionally, its open-label design and reliance on 2D-TTE rather than cardiac MRI for thrombus detection may introduce bias and affect the accuracy of outcomes.



References:

Alcalai R, Butnaru A, Moravsky G, et al. Apixaban vs. warfarin in patients with left ventricular thrombus: a prospective multicentre randomized clinical trial‡. Eur Heart J Cardiovasc Pharmacother. 2022;8(7):660-667. doi:10.1093/ehjcvp/pvab057

 

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
Exclusion criteria None reported

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

 Incidence of thromboembolic stroke within 90 days, composite incidence of thromboembolic events (stroke and systemic embolism), bleeding rates (defined by the Global Use of Strategies to Open Occluded Arteries [GUSTO])

Baseline Characteristics

  

DOAC (n= 180)

VKA (n= 769)

 

Age, years

 65.6 63.0  

Male

 125 (69.4%) 545 (70.9%)  

Concurrent antiplatelets

 84 (46.7%) 428 (55.7%)  

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

 7.8% 11.7% 0.524

Composite incidence of thromboembolic events

 33.1% 30.6% 0.524

Bleeding events

 1.1% 7.8% 0.397

Adverse Events

 N/A

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. 
References:

Bass ME, Kiser TH, Page RL 2nd, et al. Comparative effectiveness of direct oral anticoagulants and warfarin for the treatment of left ventricular thrombus. J Thromb Thrombolysis. 2021;52(2):517-522. doi:10.1007/s11239-020-02371-6

 

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

 Stroke or systemic embolism (SSE), death, bleeding events

Baseline Characteristics

  

DOAC only (n= 121)

Warfarin only (n= 236)

Therapy change (n= 64)

Neither (n= 93)

Age, years

 58.1 ± 14.9 58.2 ± 15.1 55.5 ± 12.5 61.6 ± 14.9

Male

 94 (77.7%) 170 (72%) 44 (68.8%) 71 (76.3%)

White race

 73 (60.3%) 119 (50.4%) 32 (50%) 60 (64.5%)

LVEF, %

 27.7 ± 13.8 28.2 ± 12.4 25.1 ± 11.7 26.6 ± 12.0

Thrombus size, cm2

 2.8 ± 2.1 2.8 ± 2.5 2.3 ± 1.5 2.9 ± 2.7

Antiplatelet therapy

 77 (63.6%) 164 (69.5%) 38 (59.4%) 61 (65.6%)

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

 17 14 11 12

Death

 14 32 12 57

Bleeding

 8 19 4 N/A

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

 N/A

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.
References:

Robinson AA, Trankle CR, Eubanks G, et al. Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi. JAMA Cardiol. 2020;5(6):685-692. doi:10.1001/jamacardio.2020.0652

 

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

 Thrombus resolution after 3 months, embolic events experienced

Baseline Characteristics

  

DOACs (n= 17)

VKA (n= 42)

Age, years

 57 ± 14 61 ± 13

Female

 3 (18%) 7 (17%)

Left ventricular ejection fraction, %

 41 ± 8 36 ± 12

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

 Embolic events

DOACs (n=17)

Rivaroxaban (n=4)

Apixaban (n=12)

Dabigatran (n=1)

12/17 (71%)

1 (25%)

11 (92%)

0

 2/17 (12%)

VKAs (n=42)

Acenocoumarol (n=12)

Fluindione (n=16)

Warfarin (n=14)

30 (72%)

10 (83%)

13 (82%)

7 (50%)

 4/42 (10%)

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

 N/A

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.



References:

Daher J, Da Costa A, Hilaire C, et al. Management of Left Ventricular Thrombi with Direct Oral Anticoagulants: Retrospective Comparative Study with Vitamin K Antagonists. Clin Drug Investig. 2020;40(4):343-353. doi:10.1007/s40261-020-00898-3

 

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

 LV thrombus size resolution in percentage after 3 months

Baseline Characteristics

  

Apixaban (n= 14)

Warfarin (n= 13)

Age, years

 55.4 55.0

Female

1 (7.1%) 1 (7.7%)

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

 1.0 ± 0.68 1.46 ± 0.66

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

 Mean difference, cm2 (95% CI) p-value 

Overall LVT difference between groups 

 −0.01 (−1.02 to 0.99) >0.950

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.
References:

Isa WYHW, Hwong N, Yusof AKM, et al. 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. J Clin Prev Cardiol. 2020;9:150-4. doi:10.4103/JCPC.JCPC_41_20

 

Resolution of Left Ventricular Thrombus by Vitamin K Antagonist after Failed Treatment with Apixaban in Hemodialysis Patient: Case Report

Design

 Case report

Case presentation

A 50-year-old male patient, with a history of diabetes, hypertension, paroxysmal atrial fibrillation, chronic kidney disease, coronary artery disease, heart failure with reduced ejection fraction, and treated hepatitis B infection, presented with acute myocardial infarction. The patient was subsequently revascularized with successful drug-eluting stent implantation, then placed on dual antiplatelet therapy for 24 months, followed by single antiplatelet therapy. Three years following revascularization, the patient's chronic kidney disease progressed to end-stage renal disease, and hemodialysis sessions were initiated.

Upon follow-up with the cardiology clinic, the patient was free of symptoms, with normal sinus rhythm, ejection fraction of 30%, and large apical thrombus (20×15 mm) reported. The patient's weight at the follow-up visit was 73 kg. Thus, apixaban 5 mg orally twice daily was initiated. At 3 and 6 months, there was insignificant reduction of the thrombus despite compliance with apixaban. The patient transitioned over to warfarin, after which complete resolution of thrombus was observed at 4 months of therapy.

Study Author Conclusions

We report a case of left ventricular thrombus that was successfully dissolved by warfarin after treatment with apixaban failed. This case challenges the general assumption of apixaban’s effectiveness in patients with end-stage renal disease on dialysis.
References:

Alenazi S, Alqarni F, Aldajani Y, Alzahrani A, Ahmed M. Resolution of Left Ventricular Thrombus by Vitamin K Antagonist after Failed Treatment with Apixaban in Hemodialysis Patient: Case Report. Am J Case Rep. 2023;24:e940199. Published 2023 Jun 13. doi:10.12659/AJCR.940199