Romain Chopard, MD, PhD, of the department of cardiology at the University Hospital Besancon in France, and colleagues conducted a prospective cohort study of 656 patients with acute PE discharged on DOAC therapy. The primary composite endpoint of the study was made up of all-cause death, recurrent VTE, major bleeding, and chronic thromboembolic pulmonary hypertension at 6 months.2

Dr Chopard and colleagues found that the use of nonrecommended dosing of DOACs was associated with a higher risk of adverse events. In addition, they reported that nonstandard dosing of DOACs could pose a significant risk to patients.

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“In our study, we tried to adjust for all confounding variables, but it was not a randomized trial,” Dr Chopard told Hematology Advisor. “Empiric dose reduction of DOACs was associated with 6-month adverse events in our study.”

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Possible Limitations and Clinical Recommendations

Gregory Piazza, MD, MS, of the department of medicine at Brigham and Women’s Hospital in Boston, Massachusetts, told Hematology Advisor, “The only trials that are ongoing for DOACs using nonstandard dosing are based on quality improvement initiatives to try and encourage correct dosing.”

Dr Piazza continued, “One of the issues to keep in mind with nonrandomized studies of DOACs is the fact that we may not be able to see a difference due to a lower power and sample size. There is always a chance that with a higher number of patients, some things could have been missed.”

He also pointed out that “no studies have looked at whether lower doses or underdosing could have a benefit.”

Dr Makam and colleagues noted that “current practice guidelines for management of anticoagulation in patients with VTE encourage a shared decision-making process to present personalized risk estimates to individual patients and solicitation of their concerns about treatment prior to recommending long-term preventive therapies.”

Due to their high risk-to-benefit ratio or association with adverse events, many DOACs have been removed from the market or failed to secure approval for use at certain doses.

However, Dr Makam and colleagues concluded that “DOACs should be considered safe and effective alternatives to warfarin therapy in patients with [nonvalvular atrial fibrillation] and VTE.”


  1. Makam RCP, Hoaglin DC, McManus DD, et al. Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis. PLoS One. 2018;13(5):e0197583. doi: 10.1371/journal.pone.0197583
  2. Chopard R, Serzian G, Humbert S, et al. Non-recommended dosing of direct oral anticoagulants in the treatment of acute pulmonary embolism is related to an increased rate of adverse events. Presented at: the 68th Annual Scientific Sessions and Expo of the American College of Cardiology; March 16-19, 2019; New Orleans, LA. Abstract 1042-05.

This article originally appeared on Hematology Advisor