Abstract | 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.
|
Authors | Kenneth W Mahaffey, Anne S Hellkamp, Manesh R Patel, Karen L Hannan, Kimberly Schwabe, Christopher C Nessel, Scott D Berkowitz, Jonathan L Halperin, Graeme J Hankey, Richard C Becker, Jonathan P Piccini, Günter Breithardt, Werner Hacke, Daniel E Singer, Robert M Califf, Keith A A Fox |
Journal | Circulation. Cardiovascular quality and outcomes
(Circ Cardiovasc Qual Outcomes)
Vol. 6
Issue 4
Pg. 470-8
(Jul 2013)
ISSN: 1941-7705 [Electronic] United States |
PMID | 23759472
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Anticoagulants
- Factor Xa Inhibitors
- Morpholines
- Thiophenes
- Vitamin K
- Warfarin
- Rivaroxaban
- Factor Xa
|
Topics |
- Aged
- Aged, 80 and over
- Anticoagulants
(administration & dosage, adverse effects)
- Atrial Fibrillation
(complications, diagnosis, drug therapy)
- Blood Coagulation
(drug effects)
- Clinical Protocols
- Continuity of Patient Care
- Double-Blind Method
- Drug Administration Schedule
- Drug Substitution
- Embolism
(etiology, prevention & control)
- Factor Xa
(metabolism)
- Factor Xa Inhibitors
- Female
- Humans
- International Normalized Ratio
- Male
- Middle Aged
- Morpholines
(administration & dosage, adverse effects)
- Proportional Hazards Models
- Research Design
- Risk Factors
- Rivaroxaban
- Stroke
(etiology, prevention & control)
- Thiophenes
(administration & dosage, adverse effects)
- Time Factors
- Treatment Outcome
- Vitamin K
(antagonists & inhibitors, blood)
- Warfarin
(administration & dosage, adverse effects)
|