Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

The predictive ability of the CHADS2 and CHA2DS2-VASc scores for bleeding risk in atrial fibrillation: the MAQI(2) experience.

INTRODUCTION: Guidelines recommend the assessment of stroke and bleeding risk before initiating warfarin anticoagulation in patients with atrial fibrillation. Many of the elements used to predict stroke also overlap with bleeding risk in atrial fibrillation patients and it is tempting to use stroke risk scores to efficiently estimate bleeding risk. Comparison of stroke risk scores to bleeding risk scores to predict bleeding has not been thoroughly assessed. METHODS: 2600 patients followed at seven anticoagulation clinics were followed from October 2009-May 2013. Five risk models (CHADS2, CHA2DS2-VASc, HEMORR2HAGES, HAS-BLED and ATRIA) were retrospectively applied to each patient. The primary outcome was the first major bleeding event. Area under the ROC curves were compared with C statistic and net reclassification improvement (NRI) analysis was performed. RESULTS: 110 patients experienced a major bleeding event in 2581.6 patient-years (4.5%/year). Mean follow up was 1.0±0.8years. All of the formal bleeding risk scores had a modest predictive value for first major bleeding events (C statistic 0.66-0.69), performing better than CHADS2 and CHA2DS2-VASc scores (C statistic difference 0.10 - 0.16). NRI analysis demonstrated a 52-69% and 47-64% improvement of the formal bleeding risk scores over the CHADS2 score and CHA2DS2-VASc score, respectively. CONCLUSIONS: The CHADS2 and CHA2DS2-VASc scores did not perform as well as formal bleeding risk scores for prediction of major bleeding in non-valvular atrial fibrillation patients treated with warfarin. All three bleeding risk scores (HAS-BLED, ATRIA and HEMORR2HAGES) performed moderately well.