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).