Chen, Nemin

Background: Current guidelines recommend oral anticoagulation for the prevention of stroke in most patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) are associated with lower risk of ischemic stroke and intracranial bleeding than warfarin and, therefore, may reduce risk of dementia among patients with AF. Hypothesis: AF patients initiating DOACs for stroke prevention will have lower risk of dementia than patients initiating warfarin. Methods: We used data from two US healthcare claim databases, MarketScan (2007-2015) and Optum Clinformatics (2009-2015). Using validated algorithms, we identified patients with AF who initiated oral anticoagulation. Dementia was defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 290.xx, 294.xx, or 331.0. Comorbidities and use of other medications were defined based on inpatient, outpatient, and pharmacy claims. We performed a series of head-to-head comparisons of different oral anticoagulants (warfarin, dabigatran, rivaroxaban, and apixaban) in propensity score-matched cohorts. In each database, multivariable-adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia for each comparison of propensity score-matched cohorts, adjusting for age, sex, comorbidities, use of other medications, and markers of socioeconomic status (in the Optum database only). We meta-analyzed database-specific results using a random-effects model. Results: The analysis included 307,099 AF patients from the MarketScan database and 161,346 from the Optum database, of which 6,572 and 4,391 respectively had a diagnosis of incident dementia. Mean follow up ranged between 0.7 to 2.3 years and incident of diagnosed dementia between 7 to 14 cases per 1000 person-years across different oral anticoagulant initiator groups. Patients initiating DOACs had a lower risk of incident dementia than those initiating warfarin (dabigatran: HR 0.85, 95%CI 0.71, 1.01; rivaroxaban: HR 0.85, 95%CI 0.76, 0.94; apixaban: HR 0.80, 95%CI 0.65, 0.97). There were no differences in risk of incident dementia comparing DOAC user groups (dabigatran vs. rivaroxaban: HR 1.02, 95%CI 0.79, 1.32; dabigatran vs. apixaban: HR 0.92, 95%CI 0.63, 1.36; apixaban vs. rivaroxaban: HR 1.01, 95%CI 0.86, 1.19). Conclusions: Patients with AF initiating DOACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular DOAC in relation to dementia rates.

Background Polypharmacy is highly prevalent in elderly people with chronic conditions, including atrial fibrillation ( AF ). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly patients with AF remains unaddressed. Methods and Results We studied 338 810 AF patients ≥75 years of age enrolled in the MarketScan Medicare Supplemental database in 2007–2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis (defined by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification [ ICD‐9‐CM ] codes) based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular end points (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient, and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular end points and the interaction between polypharmacy and AF treatments in relation to cardiovascular end points. Prevalence of polypharmacy was 52%. Patients with polypharmacy had increased risk of major bleeding (hazard ratio [ HR ], 1.16; 95% CI, 1.12–1.20) and heart failure ( HR , 1.33; 95% CI , 1.29–1.36) but not ischemic stroke ( HR , 0.96; 95% CI , 0.92–1.00), compared with those not receiving polypharmacy. Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. Rhythm control (versus rate control) was more effective in preventing heart failure hospitalization in patients not receiving polypharmacy ( HR , 0.87; 95% CI , 0.76–0.99) than among those with polypharmacy ( HR , 0.98; 95% CI , 0.91–1.07; P =0.02 for interaction). Conclusion Polypharmacy is common among patients ≥75 with AF , is associated with adverse outcomes, and may modify the effectiveness of AF treatments. Optimizing management of polypharmacy in AF patients ≥75 may lead to improved outcomes.

Background: Polypharmacy is highly prevalent in elderly individuals with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly AF patients remains unaddressed. Methods: We studied 338,810 AF patients ≥75 years of age with 1,761,660 active prescriptions [mean (SD), 5.1 (3.8) per patient] enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular endpoints (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular endpoints and the interaction between polypharmacy and AF treatments in relation to cardiovascular endpoints. Results: Prevalence of polypharmacy was 52% (176,007 of 338,810). Patients with polypharmacy had increased risk of major bleeding [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12, 1.20] and heart failure (HR 1.33, 95%CI 1.29, 1.36), but not of ischemic stroke (HR 0.96, 95%CI 0.92, 1.00), compared to those not with polypharmacy (Table). Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. However, rhythm control (vs. rate control) was more effective in preventing heart failure hospitalization in patients not with polypharmacy (HR 0.87, 95%CI 0.76, 0.99) than among those with polypharmacy (HR 0.98, 95%CI 0.91, 1.07, p for interaction = 0.02). Conclusion: Polypharmacy is frequent among elderly patients with AF, associated with adverse outcomes, and potentially affecting the effectiveness of AF treatments. Optimizing management of polypharmacy in elderly AF patients may lead to improved outcomes.

Background Oral anticoagulants ( OACs ) in patients with atrial fibrillation ( AF ), in addition to reducing stroke risk, could also prevent adverse cognitive outcomes. The purpose of this study was to compare the risk of dementia incidence across patients with AF initiating different OAC s. Methods and Results We identified patients with nonvalvular AF initiating OAC s in 2 US healthcare claim databases, MarketScan (2007–2015) and Optum Clinformatics (2009–2015). Dementia, comorbidities, and use of medications were defined on the basis of inpatient and outpatient claims. We performed head‐to‐head comparisons of warfarin, dabigatran, rivaroxaban, and apixaban in propensity score–matched cohorts. We calculated hazard ratios ( HR s) and 95% confidence intervals ( CI s) of incident dementia for each propensity score–matched cohort and meta‐analyzed database‐specific results. We analyzed 307 099 patients with AF from the MarketScan database and 161 346 from the Optum database, of which 6572 and 4391, respectively, had a diagnosis of incident dementia. The mean follow‐up of each cohort ranged between 0.7 and 2.2 years. Patients initiating direct OACs experienced lower rates of dementia than those initiating warfarin (dabigatran: HR , 0.85; 95% CI , 0.71–1.01; rivaroxaban: HR , 0.85; 95% CI , 0.76–0.94; apixaban: HR , 0.80; 95% CI , 0.65–0.97). There were no differences in rates of dementia comparing direct OAC user groups (dabigatran versus rivaroxaban: HR , 1.02; 95% CI , 0.79–1.32; dabigatran versus apixaban: HR , 0.92; 95% CI , 0.63–1.36; apixaban versus rivaroxaban: HR , 1.01; 95% CI , 0.86–1.19). Conclusions Patients with AF initiating direct OACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular direct OAC in relation to dementia rates.

Abstract Rationale Growing evidence suggests that compromised lung health may be linked to dementia and worsening cognitive ability. Objectives To test the hypothesis that impaired lung function or lung disease in midlife is associated with greater risk of incident dementia and mild cognitive impairment (MCI) later in life. Methods A total of 14,184 Atherosclerosis Risk in Communities study participants who underwent spirometry and were asked about lung health (1987–1989) were followed. Dementia and MCI were defined by hospitalization diagnosis codes (1987–2013) in the whole cohort and with adjudication among 42% who attended a comprehensive neurocognitive examination (2011–2013). Measurements and Main Results In analysis using adjudicated outcomes, odds of dementia or MCI were higher among participants with restrictive (multivariable-adjusted odds ratio, 1.58; 95% confidence interval, 1.14–2.19) and obstructive lung disease (multivariable-adjusted odds ratio, 1.33; 95% confidence interval, 1.07–1.64), compared with those without disease or respiratory symptoms. Associations were similar in analyses restricted to nonsmokers, and present for both Alzheimer’s disease–related dementia and cerebrovascular etiologies. Low FEV1% predicted and FVC% predicted were also associated with increased dementia risk. Conclusions Midlife lung disease and reduced lung function were associated with modestly increased odds of dementia and MCI later in life. Magnitudes of association were more pronounced for restrictive impairment than for obstructive lung disease. These associations were present in smokers and nonsmokers. If the observed associations are causal, policy and public health efforts to reduce smoking and improve air quality may have the added benefit of preventing the development of dementia and MCI.