DALLAS—New studies offer a good amount of real world data on the use of direct factor Xa inhibitors, and initial results are favorable for a new drug that quickly reverses these agents.

The real-world effectiveness, safety, and persistence data derived from Symphony Health Solutions Transactional Datasets, which include approximately 4.8 billion prescription claims in the United States for all payment types. Each rivaroxaban user was matched with up to four warfarin users based on propensity score, leaving 3,654 rivaroxaban patients to compare to 13,876 warfarin patients.

There was no significant difference in real-world rates of composite stroke and systemic embolism, major bleeding, or gastrointestinal bleeding for warfarin or rivaroxaban, but rivaroxaban was associated with a significantly higher rate of treatment persistence versus warfarin (HR = 0.66; p < 0.001). A difference in continued use was seen at 90 days (85% vs. 76%, respectively) and remained at 180 days (81% for the rivaroxaban cohort compared to 68% with warfarin).

An analysis was also presented using the Premier Comparative Hospital Database, with rivaroxaban patients (n = 2,809) again matched with up to four warfarin users (n = 11,085). Overall median length of hospital stay was about 1 day less for those receiving rivaroxaban: 4.5 days versus 5.3 days (p < 0.01). In patients using additional parenteral anticoagulants, the average hospital stay was 1.38 days shorter (p < 0.01), again favoring rivaroxaban. For patients who had the agents initiated on day 3 of their hospital stay or later, the length-of-stay was 1.72 days shorter than the matched warfarin counterparts.

The study was not designed to explain the difference in length of stay, but the authors hypothesized that it might be partly due to the time required to tailor anticoagulant therapy in those patients receiving warfarin.

Antidote Data

One drawback of the new oral Factor Xa inhibitors is that no drug has been developed to reverse the effects of these agents. Initial results from a Phase II proof-of-concept study of Portola Pharmaceuticals’ andexanet alfa (PRT4445), an investigational Factor Xa inhibitor antidote, were presented at AHA, with additional data at the American Society of Hematology annual meeting in December 2013.

The new agent was evaluated in healthy volunteers who were administered rivaroxaban and it dose-dependently reversed the anticoagulant effects. In addition, no serious adverse events were reported.

The data suggest that andexanet alfa would allow for normalization of coagulation parameters within 1 day, making it as effective as giving vitamin K to patients receiving warfarin.

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To watch exclusive interviews from AHA 2013, visit youtube.cswnews.org.

Keywords: Healthy Volunteers, Vitamin K, Blood Coagulation, Stroke, Propensity Score, Morpholines, Thiophenes, Factor Xa, Embolism, Hemorrhage, United States

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