MacLehose, Richard F.

Introduction: The prevalence of atrial fibrillation (AF) and multimorbidity increase with age; however, the burden imposed by concurrent conditions on outcomes is unknown. Therefore, we aimed to determine the effect of the number and type of comorbid conditions on outcomes in elderly individuals with incident AF. Methods: Patients with non-valvular AF 75 years and older were identified in the MarketScan Medicare Supplemental database from 2007-2015. Fourteen chronic conditions, defined by two occurrences of a diagnostic code from inpatient and outpatient claims prior to or at the time of AF diagnosis, were obtained and classified into two categories: cardiovascular (CV) or non-CV (listed in Table footnote). We used Cox regression to estimate the associations of the number and type of conditions with stroke, severe bleeding, and heart failure hospitalizations (HF). Results: Among 275,617 patients with AF (mean age 83 years, 51% women), 90% had at least one or more additional chronic conditions. The mean (SD) number of conditions per participant was 1.8 (0.9) for CV conditions and 2.1 (1.2) for non-CV conditions. Over a mean follow-up of 23 months, 7,814 strokes, 13,622 severe bleeds, and 19,252 HF events occurred. After adjustment for age, sex, the number of conditions in the other comorbidity group, an increase of one CV condition was associated with greater risk of stroke, severe bleeding, and HF (Table). In contrast, an increase in one non-CV condition was associated with a lower risk of stroke, and a small increase in bleeding and HF risk (Table). After further adjustments for frailty and medications, the strength of the associations within each group decreased across outcomes. Conclusion: CV conditions in AF patients 75 years and older are more strongly associated with stroke, HF, and bleeding than non-CV conditions. This underscores the effect of CV conditions on CV outcomes in a population in which multimorbidity is most common and health care management and delivery is complex.

Background: Multimorbidity is common in atrial fibrillation (AF); however, the impact of the number and type of comorbid conditions on death and hospitalizations is uncertain. Methods: The prevalence of 17 chronic conditions was obtained in 1430 patients with incident AF from 2000-2010 from Olmsted County, MN. Chronic conditions were ascertained electronically prior to AF and were classified into 3 groups: cardiovascular (CV), other physical, and mental. All hospitalizations and deaths were obtained through 12/31/2014. Associations of the number and type of condition and each individual condition with hospitalizations and death were determined using Andersen-Gill and Cox regression, respectively. Results: Among the 1430 patients with AF (median age 76 years, 48.6% men), the mean (SD) number of chronic conditions was 4.7 (2.7). A total of 4496 hospitalizations and 812 deaths occurred over a mean (SD) follow-up of 5.4 (4.1) years. An increase in the number of conditions of each type was associated with increased risks of death and hospitalizations (Table). Mental conditions (which included depression, anxiety, dementia, schizophrenia, and substance abuse) exhibited the strongest association with death, whereas other physical conditions exhibited the strongest association with hospitalizations. Individual predictors of death included heart failure (HF), hypertension, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), depression, dementia, and substance abuse. Predictors of hospitalizations included HF, coronary artery disease, diabetes, COPD, CKD, arthritis, osteoporosis, and substance abuse. Conclusions: Patients with AF have many comorbid conditions which are associated with death and hospitalizations. Although conditions of each type were associated with outcomes, mental conditions exhibited strongest association with death. These data highlight the importance of management of not only CV comorbidities but other physical and mental comorbidities in patients with AF.

Background and Purpose— Despite modest predictive ability for ischemic stroke (IS), the CHA 2 DS 2 -VASc score is widely used for stroke prediction in atrial fibrillation. Among patients with atrial fibrillation, we aimed to (1) compare the IS or transient ischemic attack (TIA) incidence by CHA 2 DS 2 -VASc in blacks and Hispanics versus whites; (2) compare predictive ability of CHA 2 DS 2 -VASc score for IS or TIA in blacks and Hispanics versus whites; and (3) determine improvement in predictive ability of CHA 2 DS 2 -VASc score from addition of race/ethnicity. Methods— Using data from Optum Clinformatics, a large administrative claims database, we analyzed patients with atrial fibrillation enrolled in commercial and Medicare Advantage health plans from 2009 to 2015. We computed IS or TIA incidence rates, improvement in C statistic, continuous and categorical net reclassification improvement, and relative integrated discrimination improvement from addition of race/ethnicity to CHA 2 DS 2 -VASc. Results— A total of 267 419 patients (mean age, 73.1 [SD, 12.3] years; 46.6% women; 84.2% white, 8.5% black, 7.3% Hispanic) were studied. After a mean follow-up of 22 months, there were 6202 IS or TIA events. IS or TIA incidence rates were higher in blacks than Hispanics or whites (1.65, 1.40, and 1.22 cases per 100 person-years, respectively) and increased with higher CHA 2 DS 2 -VASc, with no race/ethnicity-based differences ( P for interaction=0.17). The CHA 2 DS 2 -VASc and CHA 2 DS 2 -VASc+race/ethnicity C statistic (95% CI) were 0.679 (0.670–0.686) and 0.679 (0.671–0.688). The CHA 2 DS 2 -VASc C statistic in the 3 groups were comparable. With addition of race/ethnicity, the categorical net reclassification improvement, continuous net reclassification improvement, and relative integrated discrimination improvement were −0.045 (95% CI, −0.067 to −0.025), 0.045 (95% CI, 0.025–0.068), and 0.016 (95% CI, 0.014–0.018). Conclusions— The predictive ability of CHA 2 DS 2 -VASc for IS or TIA in atrial fibrillation is comparable among whites, blacks, and Hispanics; hence, it can be used in the latter 2 groups. Addition of race/ethnicity to the CHA 2 DS 2 -VASc does not improve its predictive ability.

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.

Background Differences in anticoagulation rates and direct oral anticoagulant use by provider specialty may identify an area of practice improvement to reduce future stroke events in patients with atrial fibrillation ( AF ). Methods and Results We examined anticoagulant prescription fills in 388 045 (mean age, 68±15 years; 59% male) patients with incident AF from the MarketScan databases between 2009 and 2014. Provider specialty and filled anticoagulant prescriptions around the time of AF diagnosis (3 months before through 6 months after) were obtained from outpatient services and pharmacy claims. We estimated the association of provider specialty (cardiology versus primary care) with filling oral anticoagulant prescriptions, adjusting for patient characteristics. The risk of stroke and bleeding events also was explored. A total of 235 739 patients (61%) had a cardiology provider claim, whereas 152 306 (39%) were exclusively managed by primary care. Patients seen by cardiology providers were more likely to fill anticoagulant prescriptions than those seen by primary care (39% versus 27%; relative risk, 1.39; 95% confidence interval [ CI ], 1.37–1.40). Differences were observed for direct oral anticoagulants (relative risk, 1.74; 95% CI , 1.71–1.78) and warfarin (relative risk, 1.24; 95% CI , 1.22–1.26). A reduced risk of stroke events was observed among those seen by cardiology providers (hazard ratio, 0.90; 95% CI , 0.86–0.94) compared with primary care, without an increased bleeding risk (hazard ratio, 1.03; 95% CI , 0.98–1.07). Conclusions Patients seen by an outpatient cardiology provider shortly after AF diagnosis were more likely to initiate oral anticoagulation and were at lower risk of future stroke events without a higher rate of bleeding. Early referral to cardiology specialists may increase initiation of anticoagulant therapies and improve outcomes in AF .

Abstract Introduction This study tested the hypotheses that late‐midlife obstructive sleep apnea (OSA) and short and long sleep duration are associated with dementia over 15 years of follow‐up. Methods A total of 1667 Atherosclerosis Risk in Communities Study participants underwent in‐home polysomnography (1996–1998) and were followed for dementia. Dementia was defined by (1) hospitalization diagnosis codes (1996–2012) and (2) a comprehensive neurocognitive examination (2011–2013) with adjudication. Results OSA and sleep duration were not associated with risk of incident dementia. When using adjudicated outcomes, severe OSA (≥30 vs. <5 apnea‐hypopnea events/hour) was associated with higher risk of all‐cause dementia (risk ratio [95% confidence interval], 2.35 [1.06–5.18]) and Alzheimer's disease dementia (1.66 [1.03–2.68]); associations were attenuated with cardiovascular risk factor adjustment. Sleeping <7 versus 8 to ≤9 hours was associated with higher risk of all‐cause dementia (2.00 [1.03–3.86]). Discussion When adjudicated outcome definitions were used, late‐midlife OSA and short sleep duration were associated with all‐cause and Alzheimer's disease dementia in later life.

Objective To assess the risk of liver injury hospitalisation in patients with atrial fibrillation (AF) after initiation of direct oral anticoagulants (DOACs) or warfarin and to determine predictors of liver injury hospitalisation in this population. Methods We studied 113 717 patients (mean age 70, 39% women) with AF included in the MarketScan Commercial and Medicare Supplemental databases with a first prescription for oral anticoagulation after 4 November 2011, followed through 31 December 2014. Of these, 56 879 initiated warfarin, 17 286 initiated dabigatran, 30 347 initiated rivaroxaban and 9205 initiated apixaban. Liver injury hospitalisation and comorbidities were identified from healthcare claims. Results During a median follow-up of 12 months, 960 hospitalisations with liver injury were identified. Rates of liver injury hospitalisation (per 1000 person-years) by oral anticoagulant were 9.0 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban) and 5.6 (apixaban). After multivariable adjustment, liver injury hospitalisation rates were lower in initiators of DOACs compared with warfarin: HR (95% CI) of 0.57 (0.46 to 0.71), 0.88 (0.75 to 1.03) and 0.70 (0.50 to 0.97) for initiators of dabigatran, rivaroxaban, and apixaban, respectively (vs. warfarin). Compared with dabigatran initiators, rivaroxaban initiators had a 56% increased risk of liver injury hospitalisation (HR 1.56, 95% CI 1.22 to 1.99). In addition to type of anticoagulant, prior liver, gallbladder and kidney disease, cancer, anaemia, heart failure and alcoholism significantly predicted liver injury hospitalisation. A predictive model including these variables had adequate discriminative ability (C-statistic 0.67, 95% CI 0.64 to 0.70). Conclusions Among patients with non-valvular AF, DOACs were associated with lower risk of liver injury hospitalisation compared with warfarin, with dabigatran showing the lowest risk.