TY - JOUR
T1 - End of Study Transition From Study Drug to Open-Label Vitamin K Antagonist Therapy
T2 - The ROCKET AF Experience
AU - Mahaffey, Kenneth W
AU - Hellkamp, Anne S
AU - Patel, Manesh R
AU - Hannan, Karen L
AU - Schwabe, Kimberly
AU - Nessel, Christopher C
AU - Berkowitz, Scott D
AU - Halperin, Jonathan L
AU - Hankey, Graeme J
AU - Becker, Richard C
AU - Piccini, Jonathan P
AU - Breithardt, Günter
AU - Hacke, Werner
AU - Singer, Daniel E
AU - Califf, Robert M
AU - Fox, Keith A A
PY - 2013/7/1
Y1 - 2013/7/1
N2 - Background- To evaluate the previously reported excess of thromboembolic events during the 30 days after the end of study (EOS) visit when participants transitioned from blinded therapy to open-label vitamin K antagonist. Methods and Results- At the EOS visit, open-label vitamin K antagonist was recommended, and the international normalized ratio (INR) was not to be measured until 3 days later to preserve blinding. We analyzed transition strategies, clinical outcomes, and INR values. Event rates are per 100 patient-years. A total of 9248 (65%) participants were taking study drug at EOS, and, between days 3 and 30, an excess of stroke and systemic embolic events were observed in participants assigned to rivaroxaban (rivaroxaban 22 events, event rate 6.42; warfarin 6 events, event rate 1.73; hazard ratio, 3.72; 95% confidence interval, 1.51-9.16; P=0.0044). No INR values were reported for ≈5% of participants transitioned to warfarin. By 30 days after EOS, 83% of the warfarin group and 52% of the rivaroxaban group had ≥1 therapeutic INR value. Median time to first therapeutic INR was 3 days in the warfarin group and 13 days in the rivaroxaban group. Conclusions- The excess of events at EOS was likely because of a period of inadequate anticoagulation in rivaroxaban participants switched to vitamin K antagonist therapy. If transition from rivaroxaban to vitamin K antagonist is needed, timely monitoring and careful dosing should be used to ensure consistent and adequate anticoagulation.
AB - Background- To evaluate the previously reported excess of thromboembolic events during the 30 days after the end of study (EOS) visit when participants transitioned from blinded therapy to open-label vitamin K antagonist. Methods and Results- At the EOS visit, open-label vitamin K antagonist was recommended, and the international normalized ratio (INR) was not to be measured until 3 days later to preserve blinding. We analyzed transition strategies, clinical outcomes, and INR values. Event rates are per 100 patient-years. A total of 9248 (65%) participants were taking study drug at EOS, and, between days 3 and 30, an excess of stroke and systemic embolic events were observed in participants assigned to rivaroxaban (rivaroxaban 22 events, event rate 6.42; warfarin 6 events, event rate 1.73; hazard ratio, 3.72; 95% confidence interval, 1.51-9.16; P=0.0044). No INR values were reported for ≈5% of participants transitioned to warfarin. By 30 days after EOS, 83% of the warfarin group and 52% of the rivaroxaban group had ≥1 therapeutic INR value. Median time to first therapeutic INR was 3 days in the warfarin group and 13 days in the rivaroxaban group. Conclusions- The excess of events at EOS was likely because of a period of inadequate anticoagulation in rivaroxaban participants switched to vitamin K antagonist therapy. If transition from rivaroxaban to vitamin K antagonist is needed, timely monitoring and careful dosing should be used to ensure consistent and adequate anticoagulation.
U2 - 10.1161/CIRCOUTCOMES.113.000132
DO - 10.1161/CIRCOUTCOMES.113.000132
M3 - Article
C2 - 23759472
SN - 1941-7705
VL - 6
SP - 470
EP - 478
JO - Circulation: Cardiovascular Quality and Outcomes
JF - Circulation: Cardiovascular Quality and Outcomes
IS - 4
ER -