Cluster randomized controlled trial of a simple warfarin maintenance dosing algorithm versus usual care among primary care practices.

Many patients using warfarin are being managed in primary care and typically achieve a lower time in therapeutic range (TTR) for the international normalized ratio (INR) than patients in specialized care. A simple warfarin maintenance dosing tool could assist primary care physicians with improving TTR. We tested whether a simple warfarin maintenance dosing algorithm can improve TTR compared with usual care among Canadian primary care physicians. Primary care practices managing warfarin therapy without an anticoagulation clinic, computer decision support system or patient self-management tools enrolled 10-30 patients with target INR range 2-3. Practices were randomized to manage warfarin maintenance with the algorithm, or as usual in 2009-2010. Primary outcome was the mean individual patient TTR, and was compared between groups with adjustment for clustering within practices. There were 13 practices randomized to the Algorithm and 15 practices to Control, enrolling 240 and 297 patients respectively, with a mean follow-up of 280 days. Mean (standard deviation; SD) TTR before the study was comparable between groups [68 % (SD 26) for usual care vs. 70 % (SD 27) for the algorithm; p = 0.49]. Dosing decisions during the study in the algorithm group were more often in agreement with the algorithm's recommendations than with usual care (81 vs. 91 %; p < 0.0001). Mean study TTR of the algorithm group was not superior to usual care: [72.1 (SE 1.7) vs. 71.4 % (SE 1.5) respectively; p = 0.73]. The simple warfarin maintenance dosing algorithm did not improve TTR compared with usual care among Canadian primary care practices.

Randomised comparison of a simple warfarin dosing algorithm versus a computerised anticoagulation management system for control of warfarin maintenance therapy.

Excellent control of the international normalised ratio (INR) is associated with improved clinical outcomes in patients receiving warfarin, and can be achieved by anticoagulation clinics but is difficult in general practice. Anticoagulation clinics have often used validated commercial computer systems to manage the INR, but these are not usually available to general practitioners. It was the objective of this study to perform a randomised trial of a simple one-step warfarin dosing algorithm against a widely used computerised dosing system. During the period of introduction of a commercial computerised warfarin dosing system (DAWN AC) to an anticoagulation clinic, patients were randomised to have warfarin dose adjustment done according to recommendations of the existing warfarin dosing algorithm or to those of the computerised system. The study tested if the computerised system was non-inferior to the existing algorithm for the primary outcome of time in therapeutic INR range of 2.0-3.0 (TTR), with a one-sided non-inferiority margin of 4.5%. There were 541 patients randomised to commercial computerised system and 527 to the algorithm. Median follow-up was 159 days. A dose recommendation was provided and followed in 91% of occasions for the computerised system and in 90% for the algorithm (p=0.03). The mean TTR was 71.0% (standard deviation [SD] 23.2) for the computerised system and 71.9% (SD 22.9) for the algorithm (difference 0.9% [95% confidence interval: -1.4% to 4.1%]; p-value for non-inferiority=0.002; p-value for superiority=0.34). In conclusion, similar maintenance control of the INR was achieved with a simple one-step dosing algorithm and a commercial computerised management system.

Quality of individual INR control and the risk of stroke and bleeding events in atrial fibrillation patients: a nested case control analysis of the ACTIVE W study.

INTRODUCTION: Time in therapeutic range (TTR) for international normalized ratio (INR) is an accepted quality measure of anticoagulation control in patient populations, but its usefulness for predicting stroke and bleeding in individuals is not well understood. MATERIALS AND METHODS: In a nested case control analysis among ACTIVE W study patients, cases with stroke and cases with bleeding were separately matched with controls. Several anticoagulation quality measures were compared, overall and in a time-dependent manner. RESULTS: 32 cases with ischemic stroke and 234 cases with bleeding in the analysis were matched in a 4:1 ratio to 122 and 865 controls, respectively. Follow-up duration was 257±154days for the stroke analysis and 222±146days for the bleeding analysis. Compared with their respective controls, the study mean TTR of both stroke cases (53.9%±25.1 vs 63.4%±24.8; p=0.055) and bleeding cases (56.2%±25.4 vs 63.4%±26.8; p<0.001) was lower. Time below range for stroke and time above range for bleeding were only greater in the last month leading up to the event, not over the entire study period. Rather, over the entire study period bleeding cases spent more time below range than controls (26.8%±25.9 vs 20.8%±24.0; p=0.001). CONCLUSIONS: TTR was lower in individual AF patients with stroke or bleeding compared with matched controls in ACTIVE W. Maintaining a high TTR, with equal importance to avoid low and high INRs, is a relevant goal of individual patient treatment to prevent stroke and bleeding.