Ventricular Thrombosis Mural Following Myocardial Infarction
Conditions
Keywords
Left ventricular thrombus, Acute myocardial infarction, Anticoagulation
Brief summary
Left Ventricular (LV) thrombus formation is witnessed in at least 10% of patients with ST segment elevation myocardial infarction (STEMI). It is a feared complication since it might increase the risk of thrombo-embolic events, including stroke. Guidelines recommend vitamin K antagonist treatment in these patients. However patients with STEMI nowadays undergo primary percutaneous coronary intervention (PCI) with coronary stent placement and consequently require dual anti-platelet therapy (ascal and P2Y12 inhibitors) to prevent stent thrombosis. Consequently, STEMI patients with LV thrombus are currently treated with triple antithrombotic therapy (aspirin, P2Y12 inhibitors, e.g. clopidogrel (75 mg/d) and vitamin K antagonist). Patients treated with triple antithrombotic therapy are subject to a strongly increased bleeding risk with a yearly incidence of 3.7% for dual anti-platelet therapy as compared to 12% for triple antithrombotic therapy. About 10% of these bleedings are cerebral. The mortality of such haemorrhagic strokes is 25%. A recent retrospective analysis did not show any beneficial effects of addition of vitamin K antagonist to dual anti-platelet therapy to prevent stroke. If vitamin K antagonist-therapy could be omitted, morbidity and mortality due to post-PCI bleedings will decrease. Therefore, a randomized trial is warranted to address this issue. Design: A multicenter, prospective, randomized, two non-inferiority trial. The objective of the study is to determine in a randomized fashion the risks and benefits of the addition of vitamin K antagonists to dual anti-platelet therapy or dual anti-platelet therapy in patients with PCI-treated STEMI and LV thrombus formation on baseline echocardiography or baseline Magnetic Resonance Imaging (MRI).
Detailed description
Design: A multicenter, prospective, randomized, non-inferiority trial with blinded evaluation of endpoints Objective: The objective of this study is to determine in a randomized fashion the risks as well as the benefits of the addition of vitamin K antagonists to dual anti-platelet therapy in patients with PCI-treated STEMI and LV thrombus formation Patients: Patients with acute myocardial infarction treated with primary PCI and LV thrombus on baseline echocardiography or baseline Magnetic Resonance Imaging. (MRI) Methods: After written informed consent has been obtained, echocardiography and MRI are performed between 7-12 days after PCI. When LV thrombus is present on baseline MRI, patients are randomized to 1. Triple antithrombotic therapy (aspirin (100 mg/d), thienopyridine class antiplatelet agent,) and vitamin K antagonist (goal INR is 2.0 to 3.0)) 2. Dual anti-platelet therapy (aspirin (100mg/d) and thienopyridine class antiplatelet agent, e.g. clopidogrel (75 mg/d). Primary Endpoint: Primary outcome is defined as the proportions of patients with new cerebral micro-infarcts at 6 months relative to baseline measured by MRI. Secondary Endpoints: The secondary endpoints as assessed at 6 and 12 months are: * the composite of vascular death, recurrent myocardial infarction, stroke or systemic embolism * presence of new cerebral mirco-bleeds * the occurrence of major and minor bleeding * neurological status and quality of life.
Interventions
DRUGAbsence of vitamin K antagonist
Dual anti-platelet therapy
Sponsors
VU University of Amsterdam
Erasmus Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Suspected Left Ventricular thrombus on echocardiography or routine Magnetic Resonance Imaging * Ongoing treatment with dual antiplatelet therapy according to ESC/ACC-AHA guidelines at the time of randomization.
Exclusion criteria
* Younger than 18 * Clinically or hemodynamically unstable * Treatment with vitamin K antagonist prior to PCI or other expected indication for vitamin K antagonist treatment (e.g. atrium fibrillation) within the next 6 months * Previous stroke or transient ischemic attack * Scheduled for major surgery (including Coronary Artery Bypass Grafting) during the course of the study * Active bleeding or high risk for bleeding contraindicating treatment with vitamin K antagonists * Contra-indication for vitamin K antagonist treatment * Chronic treatment with NSAIDs or COX-2 inhibitors for more than 4 days per week anticipated to continue during the study * Congenital cardiac disease * Presence of supraventricular or ventricular arrhythmias * Expected candidate for ICD implantation with the next 6 months * Severe renal impairment (estimated CrCl calculated by Cockcroft-Gault equation 5 30mL/min) * Known or symptomatic brain disease (such as brain tumor) * Women who are pregnant. * Any contraindication for Contrast-Enhanced Magnetic Resonance Imaging (such as pacemaker, cerebrovascular clips, known contrast allergy, claustrophobia) * Follow-up impossible (for example no fixed abode)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportions of patients with new cerebral micro-infarcts at 6 months relative to baseline measured by MRI. | 6 months relative to baseline | Primary outcome is defined as the proportions of patients with new cerebral micro-infarcts at 6 months relative to baseline measured by Magnetic Resonance Imaging. |
Secondary
| Measure | Time frame |
|---|---|
| The presence of new cerebral micro-bleeds assessed by MRI | At 6 months and 12 months relative to baseline |
| Occurrence of major and minor bleeding | At 6 and 12 months relative to baseline |
| Neurological status | At 6 and 12 months relative to baseline |
| Quality of life using a validated checklist | At 6 and 12 months relative to baseline |
| Composite of vascular death, recurrent myocardial infarction, stroke or systemic embolism | At 6 and 12 months relative to baseline |
Countries
Netherlands
Outcome results
None listed