The bleeding risk of rivaroxaban may be a significant focus of the FDA’s Cardiovascular and Renal Advisory Committee when it meets on Thursday. Briefing documents for the meeting posted this morning on the FDA website indicate that the FDA has significant safety concerns about the bleeding risk of rivaroxaban.
Here is the conclusion of the document’s executive summary
The data provided in this NDA demonstrate that for patients following THR and TKR surgery, administration of Rivaroxaban for prophylaxis of DVT and PE increases the incidence of bleeding in comparison with the active control Enoxaparin, based on the results from categories of major bleeding alone or combined with surgical site or non-major clinically relevant bleeding as assessed by Bleeding Event Adjudication Committee (AC/BE). It is known (from the label) that the most common side effect associated with using Enoxaparin is the risk of bleeding. The evidence that administration of Rivaroxaban could lead to bleeding events in significantly more patients relative to Enoxaparin amplifies this safety concern for Rivaroxaban in comparison to placebo in the setting of prophylaxis of DVT and PE following THR or TKR surgery.
Links to the FDA briefing documents for rivaroxaban:
* Notice of Meeting (html)
* Agenda (pdf)
* Roster (pdf)
* Briefing Information (htm)
* Questions (pdf)
The idea that the FDA would worry about the excess bleeding in RECORD 1, 2, and 3 and not in TRITON is the height of absurdity. As they point out in the questions, there was a single bleeding associated death in the RECORD trials and yes that patient was on Rivaroxaban. There were a total of 26 bleeding associated deaths in TRITON and 21 of the patients were on prasugrel.