Ischemic Stroke in Nonvalvular Atrial Fibrillation at Warfarin Initiation: Assessment via a Large Insurance Database.

BACKGROUND AND PURPOSE: Stroke risk may increase shortly after warfarin initiation in nonvalvular atrial fibrillation patients. Because of the brief period and limited number of events, large samples are needed to study this effect. We compared 30-day rates of ischemic stroke between nonvalvular atrial fibrillation patients initiating warfarin to nonwarfarin comparators using an insurance claims database. METHODS: We identified nonvalvular atrial fibrillation patients via 1 inpatient/2 outpatient diagnosis claims from the MarketScan database, January 1, 2009, to December 31, 2010. We studied patients initiating warfarin using prescription claims and 1:1 matched 22 669 initiators to comparators based on age, sex, diagnosis date, and warfarin propensity score. Follow-up began on initiation date; patients were censored at discontinuation/switch of therapy, disenrollment, or end of the study. The median follow-up was 415 days. Cox regression was used to study differences in ischemic stroke risks between warfarin initiators and comparators while controlling for important prognostic factors. RESULTS: Warfarin initiators were generally similar to comparators in clinical features but had higher CHADS2 scores (1.26 versus 1.19). The first 30-day ischemic stroke rate was higher among warfarin initiators than comparators (1.47%/y (27/1836) versus 0.98%/y (18/1837); P=0.18) but lower subsequently (0.81%/y [134/16 543] versus 1.09%/y [406/37 248]; P=0.002). Multivariable regression confirmed a significant interaction between follow-up and warfarin use with the adjusted hazard ratios (95% confidence intervals) for warfarin/comparator as 1.46 (0.80-2.65) in the first 30 days and 0.70 (0.57-0.85) afterward. CONCLUSIONS: Warfarin effect was qualitatively different in the first 30 days after initiation than subsequently. This is consistent with a modest increase in stroke risk occurring briefly after starting warfarin.

Apixaban compared with parenteral heparin and/or vitamin K antagonist in patients with nonvalvular atrial fibrillation undergoing cardioversion: Rationale and design of the EMANATE trial.

BACKGROUND: Stroke prevention in anticoagulation-naïve patients with atrial fibrillation undergoing cardioversion has not been systematically studied. OBJECTIVE: To determine outcomes in anticoagulation-naïve patients (defined as those receiving an anticoagulant for <48 hours during the index episode of atrial fibrillation) scheduled for cardioversion. METHODS: This is a randomized, prospective, open-label, real-world study comparing apixaban to heparin plus warfarin. Early image-guided cardioversion is encouraged. For apixaban, the usual dose is 5 mg BID with a dose reduction to 2.5 mg BID if 2 of the following are present: age >80 years, weight <60 kg, or serum creatinine >1.5 mg/dL. If cardioversion is immediate, a single starting dose of 10 mg (or 5 mg if the dose is down-titrated) of apixaban is administered. Cardioversion may be attempted up to 90 days after randomization. Patients are followed up for 30 days after cardioversion or 90 days postrandomization if cardioversion is not performed within that timeframe. Outcomes are stroke, systemic embolization, major bleeds, clinically relevant nonmajor bleeding, and death, all adjudication-blinded. STATISTICS: The warfarin-naive cohort from the ARISTOTLE study was considered the closest data set to the patients being recruited into this study. The predicted incidence of stroke, systemic embolism, and major bleeding within 30 days after randomization was approximately 0.75%. To adequately power for a noninferiority trial, approximately 48,000 participants would be needed, a number in excess of feasibility. The figure of 1,500 patients was considered clinically meaningful and achievable. CLINICAL CONTEXT: This first prospective cardioversion study of a novel anticoagulant in anticoagulation-naïve patients should influence clinical practice.

Real-world comparison of bleeding risks among non-valvular atrial fibrillation patients prescribed apixaban, dabigatran, or rivaroxaban.

Limited real-world data are available regarding the comparative safety of non-vitamin K antagonist oral anticoagulants (NOACs). The objective of this retrospective claims observational cohort study was to compare the risk of bleeding among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, or rivaroxaban. NVAF patients aged ≥18 years with a 1-year baseline period were included if they were new initiators of NOACs or switched from warfarin to a NOAC. Cox proportional hazards modelling was used to estimate the adjusted hazard ratios of any bleeding, clinically relevant non-major (CRNM) bleeding, and major inpatient bleeding within 6 months of treatment initiation for rivaroxaban and dabigatran compared to apixaban. Among 60,227 eligible patients, 8,785 were prescribed apixaban, 20,963 dabigatran, and 30,529 rivaroxaban. Compared to dabigatran or rivaroxaban patients, apixaban patients were more likely to have greater proportions of baseline comorbidities and higher CHA2DS2-VASc and HAS-BLED scores. After adjusting for baseline clinical and demographic characteristics, patients prescribed rivaroxaban were more likely to experience any bleeding (HR: 1.35, 95% confidence interval [CI]: 1.26-1.45), CRNM bleeding (HR: 1.38, 95% CI: 1.27-1.49), and major inpatient bleeding (HR: 1.43, 95% CI: 1.17-1.74), compared to patients prescribed apixaban. Dabigatran patients had similar bleeding risks as apixaban patients. In conclusion, NVAF patients treated with rivaroxaban appeared to have an increased risk of any bleeding, CRNM bleeding, and major inpatient bleeding, compared to apixaban patients. There was no significant difference in any bleeding, CRNM bleeding, or inpatient major bleeding risks between patients treated with dabigatran and apixaban.

Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population.

Estimates and projections of diagnosed incidence and prevalence of atrial fibrillation (AF) in the United States have been highly inconsistent across published studies. Although it is generally acknowledged that AF incidence and prevalence are increasing due to growing numbers of older people in the U.S. population, estimates of the rate of expected growth have varied widely. Reasons for these variations include differences in study design, covered time period, birth cohort, and temporal effects, as well as improvements in AF diagnosis due to increased use of diagnostic tools and health care awareness. The objective of this study was to estimate and project the incidence and prevalence of diagnosed AF in the United States out to 2030. A large health insurance claims database for the years 2001 to 2008, representing a geographically diverse 5% of the U.S. population, was used in this study. The trend and growth rate in AF incidence and prevalence was projected by a dynamic age-period cohort simulation progression model that included all diagnosed AF cases in future prevalence projections regardless of follow-up treatment, as well as those cases expected to be chronic in nature. Results from the model showed that AF incidence will double, from 1.2 million cases in 2010 to 2.6 million cases in 2030. Given this increase in incidence, AF prevalence is projected to increase from 5.2 million in 2010 to 12.1 million cases in 2030. The effect of uncertainty in model parameters was explored in deterministic and probabilistic sensitivity analyses. Variability in future trends in AF incidence and recurrence rates has the greatest impact on the projected estimates of chronic AF prevalence. It can be concluded that both incidence and prevalence of AF are likely to rise from 2010 to 2030, but there exists a wide range of uncertainty around the magnitude of future trends.