Treating patients for acute pulmonary embolism with direct oral anticoagulants at doses against manufacturer recommendations was associated with an increased level of adverse events, according to a recent study published in the Journal of Thrombosis and Thrombolysis.

Outcomes in patients treated for acute pulmonary embolism with direct oral anticoagulants were prospectively examined and compared between patients given manufacturer recommended doses and patients whose doses deviated from recommendations.

The primary end point was a composite of death from any cause, recurrent venous thromboembolism, major bleeding, and chronic thromboembolic pulmonary hypertension.

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Of the 1155 patients enrolled in the study, 656 (60.5%) were treated with direct oral anticoagulants. Of those patients receiving direct oral anticoagulants, 628 (95.7%) were treated with the recommended dose and 28 patients (4.3%) received nonrecommended doses. At discharge, all nonrecommended dose prescriptions were underdosed compared with the recommended dosing. The primary composite end point occurred in 7 patients (25%) in the nonrecommended dose group and in 38 patients (6.1%) in the recommended dose group (odds ratio, 3.19; 95% CI, 1.16-870; P =.02). Nonrecommended dosing was also associated with a statistically higher rate of major bleeding events (7.1% vs 1.4%; P =.008).

The study authors wrote, “In total, our results underscore the difficulty of providing treatment in compliance with guidelines and manufacturer’s drug labeling, and present an important opportunity for multidisciplinary quality improvement to improve patient safety.”

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They added, “Implementation of further strategies, such as correcting bleeding risk factors, or implanting an [inferior vena cava] filter in patients with a very high-risk of bleeding, could be safer than dose reduction.”

Disclosures: Bristol-Myers Squibb, Bayer, Boehringer-Ingelheim, and Daiichi Sankyo provided funding for this study.


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 [published online June 4, 2018]. J Thromb Thrombolysis. doi:10.1007/s11239-018-1690-6