Background:In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to prevent stroke and systemic embolism. Objective: To evaluate major bleeding (MB) in NVAF patients treated with rivaroxaban in a real-world clinical setting. Methods: From January 1, 2013, to March 31, 2014, US Department of Defense electronic health care records were queried to describe MB rates and demographics. Major bleeding was identified using a validated algorithm. Results: Of 27 467 patients receiving rivaroxaban, 496 MB events occurred in 478 patients, an incidence of 2.86 per 100 person-years (95% confidence interval: 2.61-3.13). The MB patients were older, mean (SD) age of 78.4 (7.7) vs 75.7 (9.7) years, compared with non-MB patients. Patients with MB had higher rates of hypertension (95.6% vs 75.8%), coronary artery disease (64.2% vs 36.7%), heart failure (48.5% vs 23.7%), and renal disease (38.7% vs 16.7%). Of MB patients, 63.2% were taking 20 mg, 32.2% 15 mg, and 4.6% 10 mg of rivaroxaban. Four percent of MB patients took warfarin within the prior 30 days. Major bleeding was most commonly gastrointestinal (88.5%) or intracranial (7.5%). Although 46.7% of MB patients received a transfusion, none had sufficient evidence of receiving any type of clotting factor. Fourteen died during their MB hospitalization, yielding a fatal bleeding incidence rate of 0.08 per 100 person-years (95% confidence interval: 0.05-0.14). Mean age at death was 82.4 years. Conclusions: In this large observational study, the MB rate was generally consistent with the registration trial results, and fatal bleeds were rare.

Diabetes mellitus (DM) is a common co-morbidity in those with nonvalvular atrial fibrillation (NVAF). Most patients with DM and NVAF have a CHADS-VASc score of ≥1 and should be considered for oral anticoagulation therapy for stroke prevention per treatment guidelines. The most important risk associated with anticoagulation is bleeding, which may be higher in those with NVAF plus DM. Our objective was to evaluate the incidence and characteristics of major bleeding (MB) in rivaroxaban users diagnosed with NVAF, further comparing those with DM versus those without DM, in a real-world clinical setting. Electronic medical records of >10 million patients from the Department of Defense Military Health System were queried to identify rivaroxaban users with NVAF over a 2.5-year period. Major bleeding-related hospitalization was identified by a validated case-finding algorithm. Patient characteristics, incidence and management of MB, and fatal outcomes were assessed by DM status. Of 44,793 rivaroxaban users with NVAF, 12,039 (26.9%) had DM, who were more likely men, younger, with more co-morbidity and higher CHADS-VASc scores. Major bleeding incidence was higher among those with DM compared with those without, 3.68 (95% confidence interval [CI] 3.37 to 4.03) versus 2.51 (95% CI 2.34 to 2.69) per 100 person-years, and intracranial bleeding incidence was 0.19 (95% CI 0.13 to 0.28) versus 0.25 (95% CI 0.20 to 0.31) per 100 person-years. Fatal outcomes were rare for both cohorts, 0.09 per 100 person-years. In conclusion, in this post-marketing study of 44,793 rivaroxaban users with NVAF, patients with DM had more co-morbidities and higher incidence of MB compared with those without DM.

Randomised controlled trials (RCTs) are considered the gold standard of clinical research as they use rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts. However, RCTs do not take into account the complexity of real-world clinical decision-making. To tackle this, real-world data are being increasingly used to evaluate the long-term safety and effectiveness of a given therapy in routine clinical practice and in patients who may not be represented in RCTs, addressing key clinical questions that may remain. Real-world evidence plays a substantial role in supporting the use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in clinical practice. By providing data on patient profiles and the use of anticoagulation therapies in routine clinical practice, real-world evidence expands the current awareness of NOACs, helping to ensure that clinicians are well-informed on their use to implement patient-tailored clinical decisions. There are various issues with current anticoagulation strategies, including under- or overtreatment and frequent monitoring with VKAs. Real-world studies have demonstrated that NOAC use is increasing (Dresden NOAC registry and Global Anticoagulant Registry in the FIELD-AF [GARFIELD-AF]), as well as reaffirming the safety and effectiveness of rivaroxaban previously observed in RCTs (XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation [XANTUS] and IMS Disease Analyzer). This article will describe the latest updates in real-world evidence across a variety of methodologies, such as non-interventional studies (NIS), registries and database analyses studies. It is anticipated that these studies will provide valuable clinical insights into the management of thromboembolism, and enhance the current knowledge on anticoagulant use and outcomes for patients.

Higher CHADS-VASc scores are associated with increased incidence of major bleeding in nonvalvular atrial fibrillation patients receiving rivaroxaban.

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