Anticoagulation in patients with atrial fibrillation and heart failure: Insights from the NCDR PINNACLE-AF registry.

BackgroundIn non-valvular atrial fibrillation (NVAF) patients, congestive heart failure (CHF) confers an increased risk of stroke or systemic thromboembolism. This risk is present in both heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). It is unclear if clinicians account for both types of CHF in their NVAF anticoagulation practices. Accordingly, we characterized current outpatient anticoagulation trends in NVAF patients with HFpEF compared to patients with HFrEF.MethodsThe outpatient NCDR PINNACLE-AF registry was analyzed to identify patients with NVAF and CHF. The study population was subdivided into HFpEF (ie, LVEF ≥ 40%) and HFrEF (LVEF < 40%). Anticoagulation rates by CHF group were compared and stratified by CHA2 DS2 -VASc score.ResultsA total of 340 127 patients with NVAF and CHF were identified, of whom 248 136 (73.0%) were classified as HFpEF and 91 991 (27.0%) as HFrEF. Patients with HFpEF had higher mean CHA2 DS2 -VASc scores and were more likely to be female, older, and have hypertension (P < 0.001). Unadjusted anticoagulation rates were significantly lower in patients with HFpEF compared to those with HFrEF (60.6% vs 64.2%, respectively). Lower rates of anticoagulation in the HFpEF group persisted after risk adjustment (RR: 0.93 [95% CI: 0.91, 0.94]). Stratification by CHA2 DS2 -VASc score demonstrated that lower rates of anticoagulation in patients with HFpEF persisted until a score of ≥5.ConclusionsPatients with NVAF and HFpEF have significantly lower anticoagulation rates when compared to their HFrEF counterparts. These findings suggest a potential underappreciation of HFpEF as a risk factor in patients with NVAF

Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk: Insights From the NCDR PINNACLE Registry

IMPORTANCE: Patients with atrial fibrillation (AF) are at a proportionally higher risk of stroke based on accumulation of well-defined risk factors. OBJECTIVE: To examine the extent to which prescription of an oral anticoagulant (OAC) in US cardiology practices increases as the number of stroke risk factors increases. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional registry study of outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry's PINNACLE (Practice Innovation and Clinical Excellence) Registry between January 1, 2008, and December 30, 2012. As a measure of stroke risk, we calculated the CHADS2 score and the CHA2DS2-VASc score for all patients. Using multinomial logistic regression models adjusted for patient, physician, and practice characteristics, we examined the association between increased stroke risk score and prescription of an OAC. MAIN OUTCOMES AND MEASURES: The primary outcome was prescription of an OAC with warfarin sodium or a non-vitamin K antagonist OAC. RESULTS: The study cohort comprised 429 417 outpatients with AF. Their mean (SD) age was 71.3 (12.9) years, and 55.8% were male. Prescribed treatment consisted of an OAC (192 600 [44.9%]), aspirin only (111 134 [25.9%]), aspirin plus a thienopyridine (23 454 [5.5%]), or no antithrombotic therapy (102 229 [23.8%]). Each 1-point increase in risk score was associated with increased odds of OAC prescription compared with aspirin-only prescription using the CHADS2 score (adjusted odds ratio, 1.158; 95% CI, 1.144-1.172; P < .001) and the CHA2DS2-VASc score (adjusted odds ratio, 1.163; 95% CI, 1.157-1.169; P < .001). Overall, OAC prescription prevalence did not exceed 50% even in higher-risk patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4. CONCLUSIONS AND RELEVANCE: In a large quality improvement registry of outpatients with AF, prescription of OAC therapy increased with a higher CHADS2 score and CHA2DS2-VASc score. However, a plateau of OAC prescription was observed, with less than half of high-risk patients receiving an OAC prescription

Digoxin Use and Subsequent Outcomes Among Patients in a Contemporary Atrial&nbsp;Fibrillation Cohort

BackgroundAlthough digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial.ObjectivesThis study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence of HF, to characterize the predictors of digoxin use and initiation, and to correlate digoxin use with outcomes.MethodsLongitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospective outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011.ResultsAmong 9,619 patients with AF and serial follow-up every 6 months for up to 3 years, 2,267 (23.6%) received digoxin at study enrollment, 681 (7.1%) were initiated on digoxin during follow-up, and 6,671 (69.4%) were never prescribed digoxin. After adjusting for other medications, heart rate was 72.9 beats/min among digoxin users and 71.5 beats/min among nonusers (p &lt; 0.0001). Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms, hospitalization, or mortality (in patients with HF, adjusted hazard ratio [HR] for death: 1.04; without HF, HR: 1.22). Incident digoxin use during follow-up was not associated with subsequent death in patients with HF (propensity adjusted HR: 1.05), but was associated with subsequent death in those without HF (propensity adjusted HR: 1.99).ConclusionsAfter adjustment for detailed clinical factors, digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances. Because of the multiple conflicting observational reports about digoxin's safety and possible concerns in specific clinical situations, a large pragmatic trial of digoxin therapy in AF is needed

TNF-α and TGF-β Counter-Regulate PD-L1 Expression on Monocytes in Systemic Lupus Erythematosus

Monocytes in patients with systemic lupus erythematosus (SLE) are hyperstimulatory for T lymphocytes. We previously found that the normal program for expression of a negative costimulatory molecule programmed death ligand-1 (PD-L1) is defective in SLE patients with active disease. Here, we investigated the mechanism for PD-L1 dysregulation on lupus monocytes. We found that PD-L1 expression on cultured SLE monocytes correlated with TNF-α expression. Exogenous TNF-α restored PD-L1 expression on lupus monocytes. Conversely, TGF-β inversely correlated with PD-L1 in SLE and suppressed expression of PD-L1 on healthy monocytes. Therefore, PD-L1 expression in monocytes is regulated by opposing actions of TNF-α and TGF-β. As PD-L1 functions to fine tune lymphocyte activation, dysregulation of cytokines resulting in reduced expression could lead to loss of peripheral T cell tolerance

Adherence and outcomes to direct oral anticoagulants among patients with atrial fibrillation: findings from the veterans health administration

Abstract Background The direct oral anticoagulants (DOACs) reduce the risk of stroke in moderate to high-risk patients with non-valvular atrial fibrillation (AF). Yet, concerns remain regarding its routine use in real world practice. We sought to describe adherence patterns and the association between adherence and outcomes to the DOACs among outpatients with AF. Methods We performed a retrospective cohort study of patients in the VA Healthcare System who initiated pharmacotherapy with dabigatran, rivaroxaban, or apixaban between November 2010 and January 2015 for non-valvular AF with CHA2DS2-VASc score ≥ 2. Adherence was determined using pharmacy refill data and estimated by the proportion of days covered (PDC) over the first year of therapy. Clinical outcomes, including all-cause mortality and stroke, were measured at 6 months and used to assess measures of adherence for each DOAC. Results A total of 2882 patients were included. Most were prescribed dabigatran (72.7%), compared with rivaroxaban (19.8%) or apixaban (7.5%). The mean PDC was 0.84 ± 0.20 for dabigatran, 0.86 ± 0.18 for rivaroxaban, and 0.89 ± 0.14 for apixaban (p < 0.01). The proportion of non-adherent patients, PDC <0.80, was 27.6% for all and varied according DOAC. Lower adherence to dabigatran was associated with higher risk of mortality and stroke (HR 1.07; 1.03–1.12 per 0.10 decline in PDC). Conclusions In a real-world VA population being prescribed anticoagulation for AF, more than one quarter had sub-optimal adherence. Lower adherence was associated with a higher risk of mortality and stroke. Efforts identifying non-adherent patients, and targeted adherence interventions are needed to improve outcomes

Digoxin Use and Subsequent Outcomes Among Patients in a Contemporary Atrial&nbsp;Fibrillation Cohort

BackgroundAlthough digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial.ObjectivesThis study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence of HF, to characterize the predictors of digoxin use and initiation, and to correlate digoxin use with outcomes.MethodsLongitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospective outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011.ResultsAmong 9,619 patients with AF and serial follow-up every 6 months for up to 3 years, 2,267 (23.6%) received digoxin at study enrollment, 681 (7.1%) were initiated on digoxin during follow-up, and 6,671 (69.4%) were never prescribed digoxin. After adjusting for other medications, heart rate was 72.9 beats/min among digoxin users and 71.5 beats/min among nonusers (p &lt; 0.0001). Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms, hospitalization, or mortality (in patients with HF, adjusted hazard ratio [HR] for death: 1.04; without HF, HR: 1.22). Incident digoxin use during follow-up was not associated with subsequent death in patients with HF (propensity adjusted HR: 1.05), but was associated with subsequent death in those without HF (propensity adjusted HR: 1.99).ConclusionsAfter adjustment for detailed clinical factors, digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances. Because of the multiple conflicting observational reports about digoxin's safety and possible concerns in specific clinical situations, a large pragmatic trial of digoxin therapy in AF is needed