A cautionary note has been sounded on off-label use of DOACs in patients with left ventricular thrombi, with researchers warning it is associated with a higher risk of stroke or systemic embolism than warfarin.
A US study, published in JAMA Cardiology, suggests extrapolating from DOAC use in approved indications such as non-valvular AF is problematic.
The non-randomised study comprised 514 patients with echocardiographically diagnosed LV thrombi from three tertiary care centres between 2013 and 2019.
Of the 421 patients on anticoagulant, off-label use of a DOAC was high. Slightly more than half of patients (56%) were treated with warfarin only, 29% with only a DOAC, and 15% received both due to therapy changes during the study period.
During a median follow-up of 351 days, there were 54 stroke or systemic embolism events (SSE) and 115 deaths.
The study found that DOAC treatment was associated with an increased risk of SSE events compared with warfarin use (HR 2.64 on multivariate analysis).
Analysis showed anticoagulant type was not associated with death (HR 1.19) but DOAC use was associated with a composite of death or SSE (HR 1.55).
Follow-up imaging showed anticoagulant use was not associated with thrombus resolution (HR 1.08).
The study authors said the reason for the observed higher rate of vascular events with DOAC treatment in their study was unclear.
“Anticoagulation for AF, the indication for which DOACs were developed, involves the prevention of thrombus development in addition to dissolution of existing thrombi. Only the latter is applicable to existing LV thrombi.”
“It is also possible that different classes of DOACs, and even individual agents, possess differing levels of effectiveness for treatment of LV thrombi.”
“There are also intrinsic differences between thrombi in the LV and AF-related thrombi in the left atrium and its appendage that may complicate interchangeability. Whereas AF-related thrombi are thought to be primarily caused by stasis, LV thrombosis in settings such as acute myocardial infarction is associated with both stasis and endocardial changes.”
They concluded that off-label DOAC use in LV thrombi should only be undertaken with caution.
An Editor’s Note in the journal reinforced that message saying that DOACs were not a panacea.
“Most notably, warfarin remains the standard of care for those with mechanical valves,” it said.
“Whether DOACs are equivalent to warfarin for stroke prevention, as well as what the optimal dosing and duration of therapy for DOACs is in left ventricular thrombus, can only be answered with a randomized clinical trial.”