Benefit of Oral Anticoagulant Over Antiplatelet Therapy in Atrial Fibrillation Depends on the Quality of International Normalized Ratio Control Achieved by Centers and Countries as Measured by Time in Therapeutic Range

• Published in: Circulation (New York, N.Y.) N.Y.), 2008-11, Vol.118 (20), p.2029-2037
• Main Authors: CONNOLLY, Stuart J, POGUE, Janice, EIKELBOOM, John, FLAKER, Gregory, COMMERFORD, Patrick, GRAZIA FRANZOSI, Maria, HEALEY, Jeffrey S, YUSUF, Salim
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; Aspirin - administration & dosage; Aspirin - therapeutic use; Atrial Fibrillation - drug therapy; Biological and medical sciences; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; Brazil; Cardiology. Vascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Therapy, Combination; Europe; Humans; International Normalized Ratio; Medical sciences; Middle Aged; North America; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - therapeutic use; Quality Control; South Africa; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use; Time Factors; Treatment Outcome
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.107.750000

Oral anticoagulation (OAC) therapy is effective in atrial fibrillation but requires vigilance to maintain the international normalized ratio in the therapeutic range. This report examines how differences in time in therapeutic range (TTR) between centers and between countries affect the outcomes of OAC therapy. In a posthoc analysis, the TTRs of patients on OAC in a randomized trial of OAC versus clopidogrel plus aspirin (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ACTIVE W]) were used to calculate the mean TTR for each of 526 centers and 15 countries. Proportional-hazards analysis, with and without adjustment for baseline variables, was performed, with patients stratified by TTR quartile and country. A wide variation in TTRs was found between centers, with mean TTRs for centers in the 4 quartiles of 44%, 60%, 69%, and 78%. For patients at centers below the median TTR (65%), no treatment benefit was demonstrated as measured by relative risk for vascular events of clopidogrel plus aspirin versus OAC (relative risk, 0.93; 95% confidence interval, 0.70 to 1.24; P=0.61). However, for patients at centers with a TTR above the study median, OAC had a marked benefit, reducing vascular events by >2-fold (relative risk, 2.14; 95% confidence interval, 1.61 to 2.85; P