Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi

Abstract

IMPORTANCE Left ventricular (LV) thrombi can arise in patients with ischemic and nonischemic cardiomyopathies. Anticoagulation is thought to reduce the risk of stroke or systemic embolism (SSE), but there are no high-quality data on the effectiveness of direct oral anticoagulants (DOACs) for this indication.OBJECTIVE To compare the outcomes associated with DOAC use and warfarin use for the treatment of LV thrombi. DESIGN, SETTING, AND PARTICIPANTSA cohort study was performed at 3 tertiary care academic medical centers among 514 eligible patients with echocardiographically diagnosed LV thrombi between October 1, 2013, and March 31, 2019. Follow-up was performed through the end of the study period.EXPOSURES Type and duration of anticoagulant use. MAIN OUTCOMES AND MEASURES Clinically apparent SSE.RESULTS A total of 514 patients (379 men; mean [SD] age, 58.4 [14.8] years) with LV thrombi were identified, including 300 who received warfarin and 185 who received a DOAC (64 patients switched treatment between these groups). The median follow-up across the patient cohort was 351 days (interquartile range, 51-866 days). On unadjusted analysis, DOAC treatment vs warfarin use (hazard ratio [HR], 2.71; 95% CI, 1.31-5.57; P = .01) and prior SSE (HR, 2.13; 95% CI, 1.22-3.72; P = .01) were associated with SSE. On multivariable analysis, anticoagulation with DOAC vs warfarin (HR, 2.64; 95% CI, 1.28-5.43; P = .01) and prior SSE (HR, 2.07; 95% CI, 1.17-3.66; P = .01) remained significantly associated with SSE. CONCLUSIONS AND RELEVANCEIn this multicenter cohort study of anticoagulation strategies for LV thrombi, DOAC treatment was associated with a higher risk of SSE compared with warfarin use, even after adjustment for other factors. These results challenge the assumption of DOAC equivalence with warfarin for LV thrombi and highlight the need for prospective randomized clinical trials to determine the most effective treatment strategies for LV thrombi.

Warfarin Versus Direct Oral Anticoagulants for Treating Left Ventricular Thrombus: A Systematic Review and Meta-Analysis

“…[12,14,24,25] Our results are contrary to those of Robinson et al, who reported that treatment with DOACs was associated with a higher risk of SSE compared to warfarin. [13] It is important to note that in this study, DOAC group had more patients with traditional risk factors of stroke like history of prior SSE, hyperlipidemia, atrial brillation, apical thrombus and pedunculated thrombus which could have contributed to more SSE events. Moreover, due to retrospective nature of this study, there can be some unmeasured confounders leading to increased SSE events in their study.…”

“…[10,11] The effectiveness of DOACs in treating LV thrombus is controversial, with some studies favoring their use and others not. [11][12][13][14] The large scale studies and metanalysis comparing the effectiveness and, safety of the DOACs vs warfarin in treatment of LVT are lacking. Thus, we sought to perform this systematic review and metaanalysis to compare the effectiveness and safety of warfarin vs DOACs for the treatment of LVT.…”

ST-Elevation Myocardial Infarction Presenting as Acute Limb Ischemia

“…There have been no randomized trials to our knowledge that have compared dual and triple therapy in patients with LV thrombosis complicated by thromboembolism and STEMI [10,11]. Although data from an observational study have shown an increased risk of systemic thromboembolism with the use of OAC as compared to warfarin, prospective randomized studies are lacking in this area [12]. In our case, due to hemodynamically significant groin hematoma requiring transfusion, the treatment rationale was modified to a limited duration of double therapy (apixaban and clopidogrel) with a follow-up echocardiogram to evaluate the necessity for the continuation of anticoagulation.…”

Optimal Use of Echocardiography in Management of Thrombosis After Anterior Myocardial Infarction

“…Indeed, the largest multicenter, retrospective study for LVT diagnosed by TTE argues against the assumption of equivalence between DOACs and warfarin. 44 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).…”