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Original Investigation
April 22, 2020

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

Author Affiliations
  • 1Division of Cardiovascular Medicine, Department of Medicine, University of Virginia Health System, Charlottesville
  • 2Virginia Commonwealth University Pauley Heart Center, Virginia Commonwealth University, Richmond
  • 3Department of Medicine, University of North Carolina, Chapel Hill
  • 4Department of Internal Medicine, Scripps Health, La Jolla, California
  • 5Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville
  • 6Cardiovascular Imaging Center, Department of Biomedical Engineering, University of Virginia Health System, Charlottesville
JAMA Cardiol. 2020;5(6):685-692. doi:10.1001/jamacardio.2020.0652
Key Points

Question  What are the embolic outcomes associated with using direct oral anticoagulants for left ventricular thrombi, and how do they compare with outcomes associated with using warfarin for the same indication?

Findings  In this cohort study of 514 patients with echocardiographically diagnosed left ventricular thrombi, anticoagulation with direct oral anticoagulants was associated with a higher risk of ischemic stroke and systemic emboli compared with warfarin treatment.

Meaning  Off-label use of direct oral anticoagulants for left ventricular thrombi should be undertaken with caution until clinical trial data are available to compare their use with warfarin.


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 Participants  A 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 Relevance  In 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.