Background and Study Rationale:
Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk
of stroke, most of which are cardio-embolic in origin as a result of left ventricular (LV)
thrombus formation. The risk for stroke after myocardial infarction (MI) is estimated to be
44-fold higher within the first 30 days, and remains 2 to 3 times higher than expected during
the subsequent 3 years. Anterior-wall location of a MI, in particular, can lead to the
complications of LV aneurysm and/or thrombus, which some estimate occurs in approximately up
to one-third of individuals within the first 2 weeks following an anterior MI [2].
In the absence of anti coagulation, the risk of embolization in patients with a documented LV
thrombus has been reported to be between 10 and 15 percent. Although there are no randomized
trials evaluating the efficacy of anti coagulation in patients with an LV thrombus after MI,
observational studies provide substantial supporting evidence for the recommendation to anti
coagulate patients with documented LV thrombus in order to reduce the risk of embolization.
The observation that most events occur within the first three months from the MI forms the
basis for the recommendation that anticoagulant therapy should be started early and continued
for at least three to six months after myocardial infarction.
Treatment of myocardial infarction has evolved dramatically in the past 20 years, and the
vast majorities of patients undergo early coronary intervention and receive dual anti
platelet therapy (DAPT). As a result, anterior MI alone does not warrant anti coagulation
without evidence of LV thrombus since the combination of oral anti coagulation with DAPT
carries an increased risk of bleeding. Practice guidelines recommend anti coagulation after
MI only in certain settings such as the presence of LV thrombus or atrial fibrillation [5].
Recently oral thrombin inhibitors and factor Xa inhibitors (terms as novel oral
anticoagulants - NOACS) have been introduced for stroke prevention in patients with
non-valvular atrial fibrillation [6-8]. These agents were shown to be at least as effective
as Vitamin K antagonists (VKA) such as warfarin in prevention of systemic embolism, while
having an improved safety profile with less risk of bleeding.
To date there are no data on the use of NOACS for stroke prevention in the setting of LV
thrombus after acute MI. Consequently, the effectiveness and safety of anti coagulation
therapy with these novel agents in patients with LV thrombus warrants further investigation.
The devastating impact of a stroke after an MI on morbidity and mortality, and the increasing
number of patients at risk because of improved post-MI survival, making the goal of
prevention of post MI stroke a major public health concern. The proposed study aims to
address this important clinical topic.
Objective:
To assess whether apixaban is as effective as VKA for the treatment of LV thrombus after
acute ST segment elevation MI.
Design Randomized open label non inferiority clinical trial.