Intended for healthcare professionals

Feature Investigation

Rivaroxaban: can we trust the evidence?

BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i575 (Published 03 February 2016) Cite this as: BMJ 2016;352:i575

Reliability of ROCKET-AF anticoagulation data

I would like to add my concern to that of D. Cohen regarding the quality of evidence of the ROCKET-AF trial that led to regulatory approval of rivaroxaban for stroke prevention in non-valvular atrial fibrillation.[1]
In the warfarin-treated control group, the mean Time in Therapeutic Range (TTR) was reported to be 55% - significantly less than the 62% and 64% reported respectively in the apixaban (ARISTOTLE) and dabigatran (RE-LY) trials. In the methods section of the published reports of all the above trials it is stated that TTR was calculated according to Rosendaal’s linear interpolation method.[2] However, in the Supplementary Appendix (Table 5) available online with the full text of the ROCKET-AF report at NEJM.org it is stated that “Center TTR is calculated using total number of international normalized ratio (INR) values in target range from all
warfarin subjects within a center divided by total number of INR values from all warfarin subjects within the center”.[3] This percentage is a measure of anticoagulation quality entirely different from Rosendaal’s TTR and may yield values which deviate significantly from the mean of individual TTRs. This discrepancy is confusing and raises further questions concerning the reliability of the ROCKET-AF anticoagulation data.
All individual patients’ data should be made public, if our trust in the findings of this pivotal trial is to be restored. The campaign for open access to RCT data should be intensified.

References

1. D. Cohen. Rivaroxaban: can we trust the evidence? BMJ 2016;352:i575

2. Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993;69:236-239

3. http://www.nejm.org/doi/suppl/10.1056/NEJMoa1009638/suppl_file/nejmoa100...
Last accessed 12-2-2016

Competing interests: No competing interests

14 February 2016
Constantinos Christopoulos
Physician and Haematologist
"A. Fleming" Hospital, Athens, Greece
25th Martiou St., Melissia, Athens 15127, Greece