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Treating left ventricular (LV) thrombi with direct oral anticoagulants (DOACs) instead of warfarin (Coumadin) hurt patients more than it helped them, according to the observational RED VELVT study.

Stroke and systemic embolism were a significant 2.64-fold more common in the year after patients were given DOACs as an off-label strategy to prevent embolic events than seen with warfarin, after adjustment for key factors, reported a group led by Austin Robinson, MD, of the University of Virginia Health System in Charlottesville, writing in .

Notably, there was a late separation of event curves in the study, long after the generally accepted window of time needed for anticoagulation.

"Whether these are late sequelae, unresolved LV thrombi, or an artifact of a nonrandomized study design cannot be known, especially in this study of only three centers," cautioned Ann Marie Navar, MD, PhD, of Duke Clinical Research Institute in Durham, North Carolina, and Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York City.

"It was concerning that those treated with DOACs had higher rates of stroke and systemic embolism compared with those treated with warfarin, a signal for harm that persisted despite multiple analytic approaches to adjust for confounding by treatment selection and across multiple subgroups, including by causative mechanism of cardiomyopathy and comorbid atrial fibrillation," Navar and Mehran wrote in an .

DOACs are FDA-approved to treat people with nonvalvular atrial fibrillation (Afib) and venous thromboembolism in the U.S.

Oral anticoagulation type wasn't associated with any significant difference in thrombus resolution documented on follow-up imaging in the study.

RED VELVT was performed at three centers and followed patients for a median of 351 days. Study participants all had LV thrombi on echocardiography and were divided among those who received a DOAC only (n=121), warfarin only (n=236), and those who switched at some point between the two (n=64).

Mean age was 58.4 years, and 73.7% were men. Among the few significant between-group differences were venous thromboembolism and Afib being more prevalent at baseline in the group who switched between drugs.

DOAC users mostly took apixaban (Eliquis; 76.2%), the rest took rivaroxaban (Xarelto) or dabigatran (Pradaxa).

"The reason for the observed higher rate of vascular events with DOAC treatment is unclear, particularly given the comparability of DOACs and warfarin for the treatment of Afib, but several factors can be considered," according to Robinson and colleagues.

First, anticoagulation for Afib "involves the prevention of thrombus development in addition to dissolution of existing thrombi. Only the latter is applicable to existing LV thrombi," they noted.

"It is also possible that different classes of DOACs, and even individual agents, possess differing levels of effectiveness for treatment of LV thrombi. Among the DOACs in the present analysis, most were oral factor Xa inhibitors," the authors said.

In RED VELVT, prior stroke or systemic embolism emerged as another predictor of such events over follow-up (adjusted HR 2.07, 95% CI 1.17-3.66).

Follow-up echocardiograms were performed in most patients, the first at a median 81 days and the second at 328 days.

Robinson's group acknowledged the inherent possibility of unmeasured confounding in the retrospective study. What's more, the authors lacked central core lab review of echocardiographic images and had no information on DOAC dosing or adherence throughout the study.

"Randomized clinical trials are needed to determine the most effective treatment strategies for patients with LV thrombi," they said.

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