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Background: \Anticoagulation is used for stroke prophylaxis in non-valvular atrial fibrillation, amongst other by use of the vitamin K antagonist, warfarin. Quality in warfarin therapy is often summarized by the time patients spend within the therapeutic range (percent time in therapeutic range, TTR). The correlation between TTR and the occurrence of complications during warfarin therapy has been established, but the influence of patient characteristics in that respect remains undetermined. The objective of the present papers was to examine the association between mean TTR and complication rates with adjustment for differences in relevant patient cohort characteristics., Methods: A systematic literature search was conducted in MEDLINE and Embase (2005-2015) to identify eligible studies reporting on use of warfarin therapy by patients with non-valvular atrial fibrillation and the occurrence of hemorrhage and thromboembolism. Both randomized controlled trials and observational cohort studies were included. The association between the reported mean TTR and major bleeding and stroke/systemic embolism was analyzed by random-effects meta-regression with and without adjustment for relevant clinical cohort characteristics. In the adjusted meta-regressions, the impact of mean TTR on the occurrence of hemorrhage was adjusted for the mean age and the proportion of populations with prior stroke or transient ischemic attack. In the adjusted analyses on thromboembolism, the proportion of females was, furthermore, included., Results: Of 2169 papers, 35 papers met pre-specified inclusion criteria, holding relevant information on 31 patient cohorts. In univariable meta-regression, increasing mean TTR was significantly associated with a decreased rate of both major bleeding and stroke/systemic embolism. However, after adjustment mean TTR was no longer significantly associated with stroke/systemic embolism. The proportion of residual variance composed by between-study heterogeneity was substantial for all analyses., Conclusions: Although higher mean TTR in warfarin therapy was associated with lower complication rates in atrial fibrillation, the strength of the association was decreased when adjusting for differences in relevant clinical characteristics of the patient cohorts. This study suggests that mainly the safety of warfarin therapy increases with higher mean TTR, whereas effectiveness appears not to be substantially improved. Due to the limitations immanent in the meta-regression methods, the results of the present study should be interpreted with caution. Further research on the association between the quality of warfarin therapy and risk of complications is warranted with adjustment for clinically relevant characteristics.

Background: In 2012 the European Society of Cardiology (ESC) published new guidelines on pharmacological stroke prophylaxis in non-valvular atrial fibrillation (AF). The health economics of adhering to these guidelines in clinical practice remains to be elucidated., Objective: This paper offers a health economic evaluation of two stroke-prophylactic treatment strategies: complete national adherence to the ESC guidelines on stroke prophylaxis in AF versus stroke-prophylactic treatment prior to 2012 in Denmark., Methods: A cost-utility analysis was performed to compare two treatment strategies. The first strategy reflected national guideline adherence with the use of non-vitamin K antagonist oral anticoagulants (i.e. dabigatran etexilate), warfarin, and no treatment. The second strategy reflected observed stroke prophylaxis prior to 2012 with the utilization of warfarin, acetylsalicylic acid, and no treatment. A Danish health sector perspective was adopted. A Markov model was designed and populated with information on input parameters from the literature and local cost data reflecting 2014 values. A modeled patient cohort was constructed with a risk profile intended to reflect that of the Danish patient population with AF. The applied outcome was quality-adjusted life-years (QALYs)., Results: The incremental cost-effectiveness ratio amounted to 3557 per QALY for the guideline-adherent treatment strategy (GTS) compared with the pre-2012 treatment strategy. This ratio is below a threshold of 25,000 (£20,000) per QALY. Sensitivity analyses revealed that the result was largely robust to changes in input parameters. All analyses found the GTS to be cost effective., Conclusions: Guideline adherence is a cost-effective treatment strategy compared with the strategy employed prior to 2012 for pharmacological stroke prophylaxis in AF.