Risk of interstitial lung disease in patients treated for atrial fibrillation with dronedarone versus other antiarrhythmics.

PURPOSE: To compare risks of interstitial lung disease (ILD) between patients treated with dronedarone versus other antiarrhythmics. METHODS: Parallel retrospective cohort studies were conducted in the United States Department of Defense Military Health System database (DoD) and the HealthCore Integrated Research Database (HIRD). Study patients were treated for atrial fibrillation (AF) with dronedarone, amiodarone, sotalol, or flecainide. Propensity score matching was employed to create analysis cohorts balanced on baseline variables considered potential confounders of treatment decisions. The study period of July 20, 2008 through September 30, 2014 included a 1-year baseline and minimum 6 months of follow-up, for patients with drugs dispensed between July 20, 2009 and March 31, 2014. Suspect ILD outcomes were reviewed by independent adjudicators. Cox proportional hazards regression compared risk of confirmed ILD between dronedarone and each comparator cohort. A sensitivity analysis examined the effect of broadening the outcome definition. RESULTS: A total 72 ILD cases (52 DoD; 20 HIRD) were confirmed among 27 892 patients. ILD risk was significantly higher among amiodarone than dronedarone initiators in DoD (HR = 2.5; 95% CI = 1.1-5.3, p = 0.02). No difference was detected in HIRD (HR = 1.0; 95% CI = 0.4-2.4). Corresponding risks in sotalol and flecainide exposure groups did not differ significantly from dronedarone in either database. CONCLUSIONS: ILD risk among AF patients initiated on dronedarone therapy was comparable to or lower than that of amiodarone initiators, and similar to that of new sotalol or flecainide users. This finding suggests that elevated ILD risk associated with amiodarone does not necessarily extend to dronedarone or other antiarrhythmic drugs.

Incidence and characteristics of major bleeding among rivaroxaban users with renal disease and nonvalvular atrial fibrillation.

OBJECTIVE: Patients with nonvalvular atrial fibrillation (AF) and renal disease (RD) who receive anticoagulation therapy appear to be at greater risk of major bleeding (MB) than AF patients without RD. As observed in past studies, anticoagulants are frequently withheld from AF patients with RD due to concerns regarding bleeding. The objective of this study was to evaluate the incidence and pattern of MB in those with RD, as compared to those without RD, in a population of rivaroxaban users with nonvalvular AF. METHODS: Electronic medical records of over 10 million patients from the Department of Defense Military Health System were queried to identify rivaroxaban users with nonvalvular AF. A validated algorithm was used to identify MB-related hospitalizations. RD was defined through diagnostic codes present within 6 months prior to the bleeding date for MB cases and end of study participation for non-MB patients. Data were collected on patient characteristics, comorbidities, MB management, and outcomes. RESULTS: Overall, 44,793 rivaroxaban users with nonvalvular AF were identified. RD was present among 6,921 patients (15.5%). Patients with RD had a higher rate of MB than those without RD, 4.52 per 100 person-years versus 2.54 per 100 person-years, respectively. The fatal bleeding outcome rate (0.09 per 100 person-years) was identical between those with and without RD. CONCLUSION: In this post-marketing study of 44,793 rivaroxaban users with nonvalvular AF, RD patients experienced a higher MB rate than those without RD. The higher rate of MB among those with RD may be due to the confounding effects of comorbidities.

Successful treatment of community-acquired methicillin-resistant Staphylococcus aureus purulent myopericarditis.

A previously healthy 48-year-old active duty man, who had been treated for an elbow abscess 3 weeks earlier, presented to an emergency department in Bahrain with tachycardia, pericardial friction rub and jugular venous distention. Cardiac tamponade was confirmed on transthoracic echocardiogram and he was taken for emergent pericardiocentesis. Pericardial fluid cultures grew community-acquired methicillin-resistant Staphylococcus aureus Despite ongoing treatment with intravenous vancomycin, he developed a recurrent fibrinous pericardial effusion and constrictive pericarditis requiring pericardiectomy. Though he initially did well postoperatively, he developed drug reaction with eosinophilia and systemic symptoms syndrome in response to vancomycin. He was transitioned to ceftaroline and started on high-dose steroids. He recovered during a week-long admission and was discharged home. Several weeks later at follow-up he was doing well and had resumed moderate intensity exercise.

A post-marketing assessment of major bleeding in total hip and total knee replacement surgery patients receiving rivaroxaban.

BACKGROUND: Rivaroxaban is a novel oral anticoagulant indicated for prophylaxis against deep vein thrombosis and pulmonary embolism in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery. OBJECTIVE: To evaluate major bleeding (MB) in THR/TKR patients receiving post-operative rivaroxaban. METHODS: Electronic medical records of nearly 10 million US Department of Defense (DoD) beneficiaries were queried from 1 January 2013 through 30 June 2015. Using the validated Cunningham case-finding algorithm, post-surgical MB events in rivaroxaban users were identified and analyzed. The incidence of MB was determined, and descriptive statistics were used to compare patient characteristics and other covariates in those with and without MB. Two additional methods were used to explore and identify bleeding cases that were not considered MB events per the study case-finding algorithm. RESULTS: A total of 12,429 patients received THR and/or TKR surgery, and were post-operatively prescribed rivaroxaban. Nine patients had MB, yielding an incidence proportion of 0.07% (95% CI 0.02-0.13). The alternative case-finding methods found bleeding incidences of 0.46% and 0.21%, though it is not clear whether these are clinical MB cases, since the alternative methods were not validated. CONCLUSIONS: The incidence of MB in this retrospective analysis is lower than that observed in the clinical trials of rivaroxaban. Whether this is due to lower real-world MB rates or challenges with case-finding algorithms is unclear.

Comparison of the Incidence of Major Bleeding With Rivaroxaban Use Among Nonvalvular Atrial Fibrillation Patients With Versus Without Diabetes Mellitus.

Diabetes mellitus (DM) is a common co-morbidity in those with nonvalvular atrial fibrillation (NVAF). Most patients with DM and NVAF have a CHA2DS2-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 CHA2DS2-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.

CHA2DS2-VASc Scores and Major Bleeding in Patients With Nonvalvular Atrial Fibrillation Who Are Receiving Rivaroxaban.

STUDY OBJECTIVE: Assessing stroke risk associated with nonvalvular atrial fibrillation depends on the evaluation of patient characteristics and clinical features. Clinicians must determine that the net clinical benefit from anticoagulation therapy outweighs its risk, namely, bleeding. Risk assessment for stroke is commonly performed by calculating a CHA2DS2-VASc (congestive heart failure/left ventricular dysfunction, hypertension, ≥75 years, diabetes mellitus, previous stroke or transient ischemic attack or thromboembolism, vascular disease, aged 65 to 74 years, sex female) score. It is possible that CHA2DS2-VASc scores also have a relationship with the incidence of major bleeding. We examined the relationship between CHA2DS2-VASc scores and major bleeding in rivaroxaban users with nonvalvular atrial fibrillation. METHODS: Electronic medical records of more than 10 million patients from the Department of Defense Military Health System were queried to identify patients with nonvalvular atrial fibrillation who received rivaroxaban from January 1, 2013, to June 30, 2015. Baseline characteristics of the study population were described by CHA2DS2-VASc scores and major bleeding status; major bleeding incidence was evaluated by CHA2DS2-VASc score category and for each CHA2DS2-VASc component. RESULTS: Overall, 44,793 patients met the inclusion criteria for this analysis. The major bleeding incidence rate was 2.84 (95% confidence interval 2.69 to 3.00) per 100 person-years. The incidence of major bleeding increased from 0.30 to 5.40 per 100 person-years among patients with a CHA2DS2-VASc score of 0 to 5 or higher, respectively. Fatal outcomes among patients with major bleeding were positively correlated with CHA2DS2-VASc scores; patients with higher scores had higher mortality rates. The CHA2DS2-VASc component with the highest major bleeding incidence was for vascular disease, 5.69 (95% confidence interval 5.18 to 6.24) per 100 person-years. CONCLUSION: Higher CHA2DS2-VASc scores are associated with increased incidence of major bleeding in nonvalvular atrial fibrillation patients receiving rivaroxaban.

Rivaroxaban real-world evidence: Validating safety and effectiveness in clinical practice.

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.

Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban.

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.