Anti-coagulation for left ventricular thrombus

• Summary of Guideline
• Aims
• Background
• Diagnosis
• Investigation
• Treatment / Management

Summary of Guideline

• Left ventricular thrombus complicates 4-8% of cases of acute myocardial infarction.
• Incidence is highest (19%) in anterior ST segment elevation myocardial infarction with left ventricular ejection fraction <50%
• Diagnosis is usually based on detection of left ventricular thrombus on echocardiography or magnetic resonance imaging carried out to assess left ventricular function after myocardial infarction.
• Anti-coagulation is recommended to reduce the risk of stroke and thromboembolism.
• Direct oral anti-coagulant or warfarin therapy should be initiated by the cardiology team and continued in primary care for minimum of 3 months.
• Repeat imaging and cardiology clinic follow up will be arranged at 3 months to decide whether anti-coagulation can be discontinued.
• If anticoagulation needs to be continued this will be reviewed again at 6 months

Back to top

Aims

To improve the diagnosis and management of left ventricular thrombus in adult patients following myocardial infarction.

Back to top

Background

Left ventricular (LV) thrombus is detectable by echocardiography in 4%-8% of patients with myocardial infarction receiving reperfusion therapy [1,2]. Cardiac magnetic resonance imaging (MRI) or contrast echocardiography are more sensitive at detecting left ventricular thrombus than conventional echocardiography [3]. Incidence is highest in large anterior wall infarcts and in patients who do not receive prompt reperfusion [4,5]. In a recent meta-analysis, 96% of cases of LV thrombus occurred in patients with anterior MI, with incidence reaching 19.2% in patients with anterior myocardial infarction (MI) and left ventricular ejection fraction (LVEF) <50% [6]. The presence of left ventricular thrombus leads to five-fold increased risk of thromboembolism, which occurs in 10-15% of patients without anti-coagulation [7,8]. Most thromboembolic complications occur within the first four months [8]. Echocardiographic evidence of thrombus mobility and protrusion into the left ventricular cavity are major predictors of thromboembolism [7,9-11]. Observational studies indicate that the risk of embolism can be substantially reduced by anti-coagulation with warfarin [8]. Optimum duration of anti-coagulation is unknown, although therapy is usually continued for a minimum of three months. Repeat imaging may be helpful to determine whether thrombus has resolved or become organised, although evidence is limited [4,10,12]. LV thrombus resolves within 3-6 months in the majority (88%) of cases [6]. Anticoagulation reduces the risk of embolization during thrombus resolution but does not necessarily accelerate resolution [5]. Screening of high-risk cases with acute myocardial infarction (anterior infarction + apical wall akinesis) with contrast echo or MRI has been advocated [6]. However, whether reduction in thromboembolism outweighs bleeding risk in patients with small thrombi detected on contrast echocardiography or MRI is unknown and requires further research.

As most patients with left ventricular thrombus will have received a coronary stent, combined therapy with an anticoagulant and anti-platelet agent is usually required.

Experience of direct oral anti-coagulants in patients with left ventricular thrombus is limited. However, direct oral anticoagulants (DOACs) are routinely used in combination with anti-platelet agents to reduce the risk of cardiac thromboembolism in patients with atrial fibrillation undergoing coronary stenting [13-15]. The risk of bleeding is lower when DOACs are used in combination with dual antiplatelet therapy in this setting compared to warfarin in combination with dual antiplatelet therapy [16]. There are also data to support safe and effective use of DOACs to prevent thromboembolism in patients with established thrombus in the left atrium [17,18]. It appears reasonable, therefore, to extrapolate these data to support the use of DOACs to prevent thromboembolism in patients with left ventricular thrombus. In the context of left ventricular thrombus, use of DOACs has been reported in small case series [19] and a small randomized clinical trial comparing apixaban with warfarin is ongoing [NCT02982590].

Back to top

Diagnosis

Left ventricular thrombus is usually detected incidentally on echocardiography or MRI carried out to assess left ventricular function following myocardial infarction. On rare occasions, left ventricular thrombus may be identified in patients presenting with an acute atherothrombotic event (e.g. stroke).

Late-presentation anterior infarction, suboptimal reperfusion and severe left ventricular dysfunction indicate a higher risk of left ventricular thrombus.

Back to top

Investigation

Echocardiography should be carried out in all patients following myocardial infarction before discharge from hospital to assess left ventricular ejection fraction. Most cases of left ventricular thrombus are detected incidentally on the post-myocardial infarction echocardiogram.

Screening for LV thrombus in high-risk individuals
Patients with the following clinical criteria without detectable thrombus on transthoracic echocardiography should undergo pre-discharge contrast echocardiography or cardiac MRI to exclude left ventricular thrombus [6]:

• anterior myocardial infarction +
• infarct related artery wraps around the left ventricular apex on angiography +
• apical wall akinesia on echocardiography

Detection of LV thrombus on research imaging studies
When LV thrombus is identified in patients within three months of myocardial infarction attending for a research scan, the on-call cardiology registrar or ischaemic heart disease consultant should be informed. The cardiology registrar or consultant is responsible for initiating anti-coagulation, informing primary care and arranging follow-up imaging and clinical review.

Follow-up imaging
Repeat imaging and clinical follow up should be carried out at ~3 months using the same imaging modality by which left ventricular thrombus was diagnosed (echo or MRI) – see below.

Back to top

Treatment / Management

Initiation of anti-coagulation (in-patient)
Selection of anti-coagulation therapy should be made by a cardiologist following discussion with the patient and considering renal function, body weight and requirement for concurrent anti-platelet therapy. In most cases, the cardiologist responsible for in-patients with ischaemic heart disease will be responsible for initiation of anticoagulation. All in-patients in whom LV thrombus is detected, who are not under the care of cardiology, should be discussed with the on call cardiology registrar. No oral anticoagulant has a marketing authorisation for thromboembolism prophylaxis in the setting of left ventricular thrombus. This represents an unlicenced use of a licenced medication and should be discussed with the patient and recorded in the clinical notes and discharge advice notification or correspondence.

The following options are recommended:

A: Direct oral anticoagulant (DOAC) (rivaroxaban, dabigatran, apixaban). Treatment with a DOAC should be initiated as soon as left ventricular thrombus is detected. Use the dose licensed for stroke prevention in atrial fibrillation. Edoxaban is not currently recommended due to lack of evidence.
or
B: Warfarin loading and maintenance therapy – target international normalised ratio (INR) 2.5 (range 2.0 – 3.0). Parenteral anticoagulation with low molecular weight heparin should be initiated as soon as left ventricular thrombus is detected and continued until INR ≥2.0 has been achieved. See note below regarding INR monitoring during warfarin initiation.

The information sheet ‘Anti-coagulation for left ventricular thrombus - Information for patients’ should be provided.

Points for consideration when initiating anticoagulation

Timing of diagnosis of left ventricular thrombus. This guidance relates to left ventricular thrombus detected in the early post-myocardial infarction period. If left ventricular thrombus is identified beyond the first three months after myocardial infarction, anti-coagulation in not routinely indicated unless there are features suggesting increased risk of embolisation e.g. persisting disorganized thrombus, severe left ventricular dysfunction, left ventricular aneurysm.

Baseline monitoring. Renal function, liver function, full blood count and clotting screen should be evaluated at baseline. Consider concomitant drug therapy which may interact with warfarin or DOACs in selecting therapy. Consider discussion with pharmacist.

Patients with creatinine clearance <30mL/min. Experience of DOAC use in patients with severe renal impairment is limited. Warfarin is recommended in this group.

Patients with body mass >120kg. Experience of DOAC use in this group is limited and therapeutic levels of anti-coagulation may not be achieved. Warfarin is recommended in this group. If a DOAC is used, referral to the Leeds anti-coagulation service for monitoring of levels is recommended.

INR monitoring during initiation of warfarin in patients receiving anti-platelet therapy. Care is required when initiating warfarin in this group of patients. For in-patient initiation, daily INR measurements are required. Low molecular weight heparin should be discontinued when INR ≥2.0 has been achieved. Similar arrangements should be made in conjunction with the anti-coagulation service for out-patient initiation.

Concomitant anti-platelet therapy in patients with coronary stent. Consider using DOAC rather than warfarin in patients requiring a period of dual anti-platelet therapy following coronary stenting, as the risk of bleeding is lower. Refer to ‘Leeds Teaching Hospitals guidance on anti-platelet therapy in patients receiving oral anti-coagulants for non-valvular atrial fibrillation (NVAF) undergoing Percutaneous Coronary intervention (PCI)’ on Leeds Health Pathways. In general, a DOAC should be used in combination with clopidogrel 75mg daily. Ticagrelor and prasugrel are not currently recommended at LTHT for use in combination with an anti-coagulant. If switching from ticagrelor or prasugrel in the acute setting, a 300mg loading dose of clopidogrel is recommended. Requirement for aspirin therapy should be decided on a case-by-case basis taking into account bleeding risk and atherothrombotic risk (usually maximum 4 weeks; aspirin may be omitted at cardiologist’s discretion).

Dose of DOAC
In the absence of specific dose recommendations for this indication, it is reasonable to use the dose of DOAC licensed for stroke prevention in atrial fibrillation. Refer to product summary of product characteristics (SPC) for information on contra-indications, interactions and dose adjustment in relation to patient age, renal function and body weight.

When used in conjunction with a P2Y12 inhibitor (e.g. clopidogrel) after coronary stent implantation, assess bleeding risk and consider a DOAC regime investigated in clinical trials for patients with atrial fibrillation (13-15) e.g. dabigatran 150mg twice daily (110mg twice daily if 80 years old or older) or apixaban 5mg twice daily (2.5mg twice daily if two of: 80 years old or above, creatinine >133 umol/L, weight < 60kg). In the setting of left ventricular thrombus, we recommend that rivaroxaban should be prescribed at the full anticoagulation dose of 20mg once daily (15mg once a day if CrCl 30 - 50 ml/min). Rivaroxaban15mg once daily (10mg once a day if CrCl 30 - 50 ml/min) can be considered if bleeding risk is high.

Duration of anti-coagulation and monitoring

Follow up imaging and out-patient review should be arranged with the ischaemic heart disease team.

Repeat imaging and clinical follow up should be carried out at ~3 months using the same imaging modality by which left ventricular thrombus was diagnosed (echo or MRI).

If left ventricular thrombus has resolved or appears organised at three months, anti-coagulation should be withdrawn. Dual anti-platelet therapy should be resumed in patients who have received a coronary stent to complete the recommended treatment duration (usually 12 months). The decision to stop anti-coagulation and the type and duration of subsequent anti-platelet therapy will be made by the cardiologist and clearly communicated to primary care.

If left ventricular thrombus persists at three months with adverse features (failure to organize, pedunculated appearance) anti-coagulation should be continued with further imaging and clinical review arranged at 6 months.

In some patients with adverse features (e.g. persisting disorganized thrombus, severe left ventricular dysfunction, left ventricular aneurysm) a decision for indefinite anti-coagulation may be made by the cardiologist.

In all cases, the decision to continue or stop anti-coagulation at the three-month or six-month review should be clearly communicated to the patient’s GP.

If during therapy the patient develops a condition which may increase the risk of anti-coagulation, e.g. anaemia, thrombocytopenia, significant bleeding, significant deterioration of renal function, their management should be discussed with the cardiologist.