Risk stratification and prevention of systemic thromboembolism
Even in the primary angioplasty era, LVT formation after MI indicated a
fourfold increased embolic risk and twofold long-term mortality
rate.28 The risk of embolic events is the highest
during the first or second week after MI with a decline over the
subsequent 3 months.29-31 Thrombi prone to
embolization are those that protrude in the LV cavity (exposed to the
blood flow on several sides) and have a free mobility (which indicates
thrombus friability), unlike the mural thrombi that appear flat and
parallel to the endocardial surface (Fig.2).32, 33
Other echocardiographic LVT characteristics, such as thrombus size,
central echolucency or hyperkinesia of the myocardial segments adjacent
to the thrombus, were found to be associated with an increased risk of
embolism in some studies, but were not confirmed by
others.1 However, it is critically important to
appreciate that a spontaneous time-course variation in the LVT
morphologic aspects is common in the first several months after MI
(Fig.3). Importantly, up to 40% of embolism episodes occur in patients
whose thrombi are neither protuberant nor mobile.34Therefore, when LVT is detected, anticoagulation is essential to prevent
systemic thromboembolism regardless of the echocardiographic phenotype.
Current guidelines recommend vitamin K antagonists as the first-choice
therapy in this patient population.20, 35, 36Thrombus resolution with warfarin occurs frequently (80-85% at 6
months) after an anterior MI. It could be argued that LVT regression may
be at least partially the consequence of thrombus embolization. However,
although asymptomatic embolization cannot be excluded, LVT regression
seems not associated with increased embolic risk.37
The thromboembolic risk appears to be lower in the current reperfusion
era, with a cumulative incidence of 5.5%.6 This is
due, at least in part, to the higher time in therapeutic range usually
achieved during warfarin treatment. Indeed, the rate of systemic
embolism is quite low (3%) in patients with a time in therapeutic range
≥50%.38
Of note, no data are currently available from clinical trials evaluating
the safety and efficacy of anticoagulation in the treatment of LVT after
MI. This gap in knowledge is important considering that the
antithrombotic options for LVT have become more complicated for a series
of reasons, including patient characteristics, with progressively older
subjects, affected by multiple comorbidities, the need for a combination
of chronic anticoagulation and various antiplatelet therapy schemes, and
the emergence of direct oral anticoagulants (DOACs), widely used in the
setting of thromboembolic prophylaxis for atrial fibrillation or
pulmonary embolism. Therefore, clinicians must rely on available data
from trials to guide the treatment of these different thromboembolic
conditions, which substantially showed that the combination of oral
anticoagulants with two antiplatelets (triple therapy) increases the
bleeding risk compared with less potent antithrombotic regimens after
MI. On the other hand, observational data suggest that triple therapy
regimens may not prevent LVT formation.21, 39
The efficacy of DOACs in the treatment of LVT seems comparable to the
efficacy of warfarin, but current data are limited to small case series
and meta-analysis of case reports40-42. Nevertheless,
the intrinsic differences in thrombogenesis between LVT and atrial
fibrillation-related thrombi, either in the left atrium and its
appendage, can make anticoagulants non-interchangeable and request a
better assessment of the off-label use of DOACs in terms of benefits and
risks. Indeed, the largest multicenter, retrospective study for LVT
diagnosed by TTE argues against the assumption of equivalence between
DOACs and warfarin.43 Trials comparing DOACs and
warfarin in the treatment of LVT are ongoing in China, Malaysia and
Israel (ClinicalTrials.gov number NCT03764241, NCT02982590 and
NCT03232398, respectively).