Impact of California's mandate for antimicrobial stewardship programs on rates of methicillin-resistant Staphylococcus aureus and Clostridioides difficile infection in acute-care hospitals.

OBJECTIVE: To estimate the impact of California's antimicrobial stewardship program (ASP) mandate on methicillin-resistant Staphylococcus aureus (MRSA) and Clostridioides difficile infection (CDI) rates in acute-care hospitals. POPULATION: Centers for Medicare and Medicaid Services (CMS)-certified acute-care hospitals in the United States. DATA SOURCES: 2013-2017 data from the CMS Hospital Compare, Provider of Service File and Medicare Cost Reports. METHODS: Difference-in-difference model with hospital fixed effects to compare California with all other states before and after the ASP mandate. We considered were standardized infection ratios (SIRs) for MRSA and CDI as the outcomes. We analyzed the following time-variant covariates: medical school affiliation, bed count, quality accreditation, number of changes in ownership, compliance with CMS requirements, % intensive care unit beds, average length of stay, patient safety index, and 30-day readmission rate. RESULTS: In 2013, California hospitals had an average MRSA SIR of 0.79 versus 0.94 in other states, and an average CDI SIR of 1.01 versus 0.77 in other states. California hospitals had increases (P < .05) of 23%, 30%, and 20% in their MRSA SIRs in 2015, 2016, and 2017, respectively. California hospitals were associated with a 20% (P < .001) decrease in the CDI SIR only in 2017. CONCLUSIONS: The mandate was associated with a decrease in CDI SIR and an increase in MRSA SIR.

Are Rates of Methicillin-Resistant Staphylococcus aureus and Clostridioides difficile Associated With Quality and Clinical Outcomes in US Acute Care Hospitals?

The purpose of this study was to examine the association between rates of methicillin-resistant Staphylococcus aureus (MRSA)/Clostridioides difficile and quality and clinical outcomes in US acute care hospitals. The population was all Medicare-certified US acute care hospitals with MRSA/C difficile standardized infection ratio (SIR) data available from 2013 to 2017. Hospital-level data from the Centers for Medicare & Medicaid Services were used to estimate hospital and time fixed effects models for 30-day hospital readmissions, length of stay, 30-day mortality, and days in the intensive care unit. The key explanatory variables were SIR for MRSA and C difficile. No association was found between MRSA or C difficile rates and any of the 4 outcomes. The null results add to the mixed evidence in the field, but there are likely residual confounding factors. Future research should use larger samples of patient-level data and appropriate methods to provide evidence to guide efforts to tackle antimicrobial resistance.

Effectiveness and Safety of Oral Anticoagulants among NVAF Patients with Obesity: Insights from the ARISTOPHANES Study.

This ARISTOPHANES analysis examined stroke/systemic embolism (SE) and major bleeding (MB) among a subgroup of nonvalvular atrial fibrillation (NVAF) patients with obesity prescribed warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) in order to inform clinical decision making. A retrospective observational study was conducted among NVAF patients who were obese and initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013-30 September 2015, with data pooled from CMS Medicare and four US commercial claims databases. Propensity score matching was completed between NOACs and against warfarin in each database, and the results were pooled. Cox models were used to evaluate the risks of stroke/SE and MB. A total of 88,461 patients with obesity were included in the study. Apixaban and rivaroxaban were associated with a lower risk of stroke/SE vs. warfarin (HR: 0.63, 95% CI: 0.49-0.82 and HR: 0.84, 95% CI: 0.72-0.98). Dabigatran was associated with a similar risk of stroke/SE compared to warfarin. Compared with warfarin, apixaban and dabigatran had a lower risk of MB (HR: 0.54, 95% CI: 0.49-0.61 and HR: 0.75, 95% CI: 0.63-0.91). Rivaroxaban was associated with a similar risk of MB compared to warfarin. In this high-risk population with obesity, NOACs had a varying risk of stroke/SE and MB vs. warfarin.

Effectiveness and Safety of Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Diabetes Mellitus.

OBJECTIVE: To address gaps in the data comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among patients with nonvalvular atrial fibrillation (NVAF) and diabetes. PATIENTS AND METHODS: A retrospective study was conducted on patients with NVAF and diabetes newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with Medicare data from the US Centers for Medicare & Medicaid Services and 4 other US commercial claims databases. One-to-one propensity score matching was completed between NOACs and warfarin and between NOACs in each database, and the results were pooled. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and major bleeding (MB). RESULTS: A total of 154,324 patients were included in the 6 matched cohorts, with a mean follow-up time of 6 to 8 months. Compared with warfarin, apixaban (hazard ratio [HR], 0.67; 95% CI, 0.57-0.77) and rivaroxaban (HR, 0.79; 95% CI, 0.71-0.89) were associated with a lower risk of stroke/SE; dabigatran (HR, 0.84; 95% CI, 0.67-1.07) was associated with a similar risk of stroke/SE. Apixaban (HR, 0.60; 95% CI, 0.56-0.65) and dabigatran (HR, 0.78; 95% CI, 0.69-0.88) were associated with a lower risk of MB; rivaroxaban (HR, 1.02; 95% CI, 0.94-1.10) was associated with a similar risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of MB. Compared with rivaroxaban, dabigatran was associated with a lower risk of MB. CONCLUSION: This study-the largest observational study to date of patients with NVAF and diabetes taking anticoagulants-found that NOACs were associated with variable rates of stroke/SE and MB compared with warfarin. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03087487.

Association between statewide adoption of the CDC's Core Elements of Hospital Antimicrobial Stewardship Programs and rates of methicillin-resistant Staphylococcus aureus bacteremia and Clostridioides difficile infection in the United States.

OBJECTIVE: To measure the association between statewide adoption of the Centers for Disease Control and Prevention's (CDC's) Core Elements for Hospital Antimicrobial Stewardship Programs (Core Elements) and hospital-associated methicillin-resistant Staphylococcus aureus bacteremia (MRSA) and Clostridioides difficile infection (CDI) rates in the United States. We hypothesized that states with a higher percentage of reported compliance with the Core Elements have significantly lower MRSA and CDI rates. PARTICIPANTS: All US states. DESIGN: Observational longitudinal study. METHODS: We used 2014-2016 data from Hospital Compare, Provider of Service files, Medicare cost reports, and the CDC's Patient Safety Atlas website. Outcomes were MRSA standardized infection ratio (SIR) and CDI SIR. The key explanatory variable was the percentage of hospitals that meet the Core Elements in each state. We estimated state and time fixed-effects models with time-variant controls, and we weighted our analyses for the number of hospitals in the state. RESULTS: The percentage of hospitals reporting compliance with the Core Elements between 2014 and 2016 increased in all states. A 1% increase in reported ASP compliance was associated with a 0.3% decrease (P < .01) in CDIs in 2016 relative to 2014. We did not find an association for MRSA infections. CONCLUSIONS: Increasing documentation of the Core Elements may be associated with decreases in the CDI SIR. We did not find evidence of such an association for the MRSA SIR, probably due to the short length of the study and variety of stewardship strategies that ASPs may encompass.

Clinical outcomes and treatment patterns among Medicare patients with nonvalvular atrial fibrillation (NVAF) and chronic kidney disease.

BACKGROUND: Patients with nonvalvular atrial fibrillation (NVAF) and chronic kidney disease (CKD) have increased risk of adverse outcomes. This study evaluated treatment with oral anticoagulants and outcomes in elderly NVAF patients with CKD. METHODS: Retrospective observational cohort study of US Medicare fee-for-service patients aged ≥66 years with comorbid CKD (advanced: Stage 4 and higher; less advanced: Stages 1-3) and a new NVAF diagnoses from 2011-2013. All-cause mortality, stroke, major bleeding, and myocardial infarction rates were estimated for 1 year post-NVAF diagnosis. Associations between CKD stage and outcomes were evaluated with multivariate-adjusted Cox regression. We assessed oral anticoagulant (OAC) receipt within 90 days post-NVAF diagnosis and associations between OAC receipt and outcomes. RESULTS: There were 198,380 eligible patients (79,681 with advanced CKD). After adjustment for age, gender, and comorbidities, advanced CKD was associated with increased mortality (Stage 5 HR 1.47; 95% CI 1.42-1.52), MI (HR 1.48; 95% CI 1.33-1.64), stroke (HR 1.23; 95% CI 1.11-1.37) and major bleed (HR 1.44; 95% CI 1.36-1.53) risks. Among Medicare Part D enrollees who survived ≥90 days post-NVAF diagnosis, 65-71% received no OACs in the first 90 days. Those receiving warfarin (HR 0.73; 95% CI 0.71-0.75) or DOACs (HR 0.52; 95% CI 0.49-0.56) within the first 90 days had reduced mortality in the period 90 days to 1 year following NVAF diagnosis compared to those without. CONCLUSION: Elderly NVAF patients with advanced CKD (Stage 4 or higher) had higher mortality risks and serious clinical outcomes than those with less advanced CKD (Stage 1-3). OAC use was low across all CKD stages, but was associated with a lower mortality risk than no OAC use in the first year post-NVAF diagnosis.

Comparisons between Oral Anticoagulants among Older Nonvalvular Atrial Fibrillation Patients.

OBJECTIVES: Older adult patients are underrepresented in clinical trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. This subgroup analysis of the ARISTOPHANES study used multiple data sources to compare the risk of stroke/systemic embolism (SE) and major bleeding (MB) among very old patients with nonvalvular atrial fibrillation (NVAF) prescribed NOACs or warfarin. DESIGN: Retrospective observational study. SETTING: The Centers for Medicare & Medicaid Services and three US commercial claims databases. PARTICIPANTS: A total of 88 582 very old (aged ≥80 y) NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015. MEASUREMENTS: In each database, six 1:1 propensity score matched (PSM) cohorts were created for each drug comparison. Patient cohorts were pooled from all four databases after PSM. Cox proportional hazards models were used to estimate hazard ratios (HRs) of stroke/SE and MB. RESULTS: The patients in the six matched cohorts had a mean follow-up time of 7 to 9 months. Compared with warfarin, apixaban (HR = .58; 95% confidence interval [CI] = .49-.69), dabigatran (HR = .77; 95% CI = .60-.99), and rivaroxaban (HR = .74; 95% CI = .65-.85) were associated with lower risks of stroke/SE. For MB, apixaban (HR = .60; 95% CI = .54-.67) was associated with a lower risk; dabigatran (HR = .92; 95% CI = .78-1.07) was associated with a similar risk, and rivaroxaban (HR = 1.16; 95% CI = 1.07-1.24) was associated with a higher risk compared with warfarin. Apixaban was associated with a lower risk of stroke/SE and MB compared with dabigatran (stroke/SE: HR = .65; 95% CI = .47-.89; MB: HR = .60; 95% CI = .49-.73) and rivaroxaban (stroke/SE: HR = .72; 95% CI = .59-.86; MB: HR = .50; 95% CI = .45-.55). Dabigatran was associated with a lower risk of MB (HR = .77; 95% CI = .67-.90) compared with rivaroxaban. CONCLUSION: Among very old NVAF patients, NOACs were associated with lower rates of stroke/SE and varying rates of MB compared with warfarin. J Am Geriatr Soc 67:1662-1671, 2019.

Effectiveness and safety of oral anticoagulants in older adults with non-valvular atrial fibrillation and heart failure.

Direct oral anticoagulants (DOACs) are at least as efficacious and safe as warfarin among non-valvular atrial fibrillation (NVAF) patients; limited evidence is available regarding NVAF patients with heart failure (HF). US Medicare enrollees with NVAF and HF initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected. Propensity score matching and Cox models were used to estimate the risk of stroke/systemic embolism (SE), major bleeding (MB), and major adverse cardiac events (MACE) comparing DOACs versus warfarin and DOACs versus DOACs. We identified 10,570 apixaban-warfarin, 4,297 dabigatran-warfarin, 15,712 rivaroxaban-warfarin, 4,263 apixaban-dabigatran, 10,477 apixaban-rivaroxaban, and 4,297 dabigatran-rivaroxaban matched pairs. Compared to warfarin, apixaban had lower rates of stroke/SE (hazard ratio = 0.64, 95% confidence interval = 0.48-0.85), MB (hazard ratio = 0.66, 0.58-0.76), and MACE (hazard ratio = 0.73,0.67-0.79); dabigatran and rivaroxaban had lower rates of MACE (hazard ratio = 0.87,0.77-0.99; hazard ratio = 0.84, 0.79-0.89, respectively). Rivaroxaban had a lower stroke/SE rate (hazard ratio = 0.65, 0.52-0.81) and higher MB rate (hazard ratio = 1.18, 1.08-1.30) versus warfarin. Compared to dabigatran and rivaroxaban, apixaban had lower MB (hazard ratio = 0.71, 0.57-0.89; hazard ratio = 0.55, 0.49-0.63) and MACE rates (hazard ratio = 0.80, 0.69-0.93; hazard ratio = 0.86, 0.79-0.94), respectively. All DOACs had lower MACE rates versus warfarin; differences were observed in stroke/SE and MB. Our findings provide insights about OAC therapy among NVAF patients with HF.