Chamberlain, Alanna M

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.

Objectives To investigate the effect of the number and type of comorbid conditions on death and hospitalizations in individuals with incident heart failure ( HF ). Design Population‐based cohort study. Setting Olmsted County, Minnesota. Participants Olmsted County, Minnesota, residents with incident HF from 2000 to 2010 (mean age 76 ± 14, 56% female) (N = 1,714). Measurements The prevalence of 16 chronic conditions obtained at HF diagnosis classified into three groups: cardiovascular ( CV ) related, other physical, and mental. Results The mean number of conditions per participant was 2.6 ± 1.5 for CV ‐related conditions, 1.3 ± 1.1 for other physical conditions, and 0.30 ± 0.61 for mental conditions. After a mean follow‐up of 4.2 years, 1,073 deaths and 6,306 hospitalizations had occurred. After adjustment for age, sex, ejection fraction, in‐ or outpatient status, and number of other conditions, an increase of one other physical condition was associated with a 14% ( HR = 1.14, 95% CI = 1.08–1.20) greater risk of death and a 26% ( HR = 1.26, 95% CI = 1.20–1.32) greater risk of hospitalization, and an increase of one mental condition was associated with a 31% ( HR = 1.31, 95% CI = 1.19–1.44) greater risk of death and an 18% ( HR = 1.18, 95% CI = 1.07–1.29) greater risk of hospitalization. In contrast, an increase of one CV ‐related condition was not associated with greater risk of death and was associated with a 10% ( HR = 1.10, 95% CI = 1.06–1.15) greater risk of hospitalization. Conclusion CV ‐related conditions are the most common type of comorbid conditions in individuals with HF , but other physical and mental conditions are more strongly associated with death and hospitalizations. This underscores the effect of non‐ CV conditions on outcomes in HF .

Background While atrial fibrillation is a recognized risk factor for stroke, contemporary data on trends in stroke incidence after the diagnosis of atrial fibrillation are scarce. Methods and Results Olmsted County, MN residents with incident atrial fibrillation or atrial flutter (collectively referred to as AF ) from 2000 to 2010 were identified. Cox regression determined associations of year of AF diagnosis with ischemic stroke and transient ischemic attack ( TIA ) occurring through 2013. Among 3247 AF patients, 321 (10%) had an ischemic stroke/ TIA over a mean of 4.6 years (incidence rate [95% CI ] per 100 person‐years: 2.14 [1.91–2.38]). Two hundred thirty‐nine (7%) of 3265 AF patients experienced an ischemic stroke (incidence rate: 1.54 [1.35–1.75]). The risk of both outcomes remained unchanged over time after adjusting for demographics and comorbidities (hazard ratio [95% CI ] per year of AF diagnosis: 1.00 [0.96–1.04] for ischemic stroke/ TIA ; 1.01 [0.96–1.06] for ischemic stroke only). In analyses restricted to patients with prescription information, the rates of anticoagulation use did not change over time, reaching 50.8% at 1 year after AF diagnosis. Further adjustment for anticoagulation use did not alter the temporal trends in stroke incidence (hazard ratio [95% CI ] per year of AF diagnosis: 1.06 [0.97–1.15] for ischemic stroke/ TIA ; 1.08 [0.98–1.20] for ischemic stroke only). Conclusions Strokes/ TIA s are frequent after AF , occurring in 10% of patients after 5 years of follow‐up. The occurrence of stroke/ TIA did not decline over the last decade, which may be influenced by a leveling off of anticoagulation use. This concerning trend has major public health implications.

Objective The goal of this study was to identify distinct frailty trajectories (clusters of individuals following a similar progression of frailty over time) in an ageing population and to determine social and behavioural factors associated with frailty trajectories. Design Population-based cohort study. Setting Olmsted County, Minnesota. Participants Olmsted County, Minnesota residents aged 60–89 in 2005. Primary outcome measure Changes in frailty over an 8-year period from 2005 to 2012, measured by constructing a yearly frailty index. Frailty trajectories by decade of age were determined using k-means cluster modelling for longitudinal data. Results After adjustment for age and sex, all social and behavioural factors (education, marital status, living arrangements, smoking status and alcohol use) were significantly associated with frailty trajectories in those aged 60–69 and 70–79 years. After further adjustment for baseline frailty, the likelihood of being in the high frailty trajectory was greatest among those reporting concerns from relatives/friends about alcohol consumption (OR (95% CI) 2.26 (1.19 to 4.29)) and those with less than a high school education (OR (95% CI) 1.98 (1.32 to 2.96)) in the 60–69 year olds. In the 70–79 year olds, the largest associations were observed among those with concerns from oneself about alcohol consumption (OR (95% CI) 1.92 (1.23 to 3.00)), those with less than a high school education (OR (95% CI) 1.57 (1.12 to 2.22)), and those living with family (vs spouse; OR (95% CI) 1.76 (1.05 to 2.94)). No factors remained associated with frailty trajectories in the 80–89 year olds after adjustment for baseline frailty. Conclusions Social and behavioural factors are associated with frailty, with stronger associations observed in younger ages. Recognition of social and behavioural factors associated with increasing frailty may inform interventions for individuals at risk of worsening frailty, specifically when targeted at younger individuals.

Objectives To identify distinct frailty trajectories (clusters of individuals following a similar progression of frailty over time) in an aging population and to estimate associations between frailty trajectories and emergency department visits, hospitalizations, and all‐cause mortality. Design Population‐based cohort study. Setting Olmsted County, Minnesota. Participants Olmsted County, Minnesota residents aged 60–89 in 2005. Measurements Longitudinal changes in frailty between 2005 and 2012 were measured by constructing a yearly Rockwood frailty index incorporating body mass index, 17 comorbidities, and 14 activities of daily living. The frailty index measures variation in health status as the proportion of deficits present of the 32 considered (range 0–1). Results Of the 16,443 Olmsted County residents aged 60–89 in 2005, 12,270 (74.6%) had at least 3 years of frailty index measures and were retained for analysis. The median baseline frailty index increased with age (0.11 for 60–69, 0.14 for 70–79, 0.19 for 80–89). Three distinct frailty trajectories were identified in individuals aged 60–69 at baseline and two trajectories in those aged 70–79 and 80–89. Within each decade of age, increasing frailty trajectories were associated with greater risks of emergency department visits, hospitalization, and all‐cause mortality, even after adjustment for baseline frailty index. Conclusion The number of frailty trajectories differed according to age. Within each age group, those in the highest frailty trajectory had greater healthcare use and worse survival. Frailty trajectories may offer a way to target aging individuals at high risk of hospitalization or death for therapeutic or preventive interventions.

Background— Contemporary data are lacking on the prognostic importance of heart failure (HF) after myocardial infarction (MI). We evaluated the prognostic impact of HF post MI according to preserved/reduced ejection fraction and the timing of its occurrence. Methods and Results— All Olmsted County, Minnesota, residents (n=2596) with incident MI diagnosed in 1990 to 2010 and no prior HF were followed through March 2013. Cox models were used to examine (1) the hazard ratios for death associated with HF type and timing and (2) secular trends in survival by HF status. During a mean follow-up of 7.6 years, there were 1116 deaths, 634 in the 902 patients who developed HF (70%) and 482 in the 1694 patients who did not develop HF (28%). After adjustment for age and sex, HF as a time-dependent variable was strongly associated with mortality (hazard ratio =3.31, 95% confidence interval: 2.93–3.75), particularly from cardiovascular causes (hazard ratio =4.20, 95% confidence interval: 3.50–5.03). Further adjustment for MI severity and comorbidity, acute treatment, and recurrent MI moderately attenuated these associations (hazard ratio =2.49 and 2.94 for all-cause and cardiovascular mortality, respectively). Mortality did not differ by ejection fraction, but was higher for delayed- versus early-onset HF ( P for heterogeneity =0.002). The age- and sex-adjusted 5-year survival estimates in 2001 to 2010 versus 1990 to 2000 were 82% and 81% among HF-free and 61% and 54% among HF patients, respectively ( P for heterogeneity of trends =0.05). Conclusions— HF markedly increases the risk of death after MI. This excess risk is similar regardless of ejection fraction but greater for delayed- versus early-onset HF. Mortality after MI declined over time, primarily as a result of improved HF survival.

ABSTRACTBackgroundThe authors sought to estimate incremental economic impact of atrial fibrillation (AF) and the timing of its onset in myocardial infarction (MI) patients.HypothesisConcurrent AF and its timing are associated with higher costs in MI patients.MethodsThis retrospective cohort study included incident MI patients from Olmsted County, Minnesota, treated between November 1, 2002, and December 31, 2010. We compared inflation‐adjusted standardized costs accumulated between incident MI and end of follow‐up among 3 groups by AF status and timing: no AF, new‐onset AF (within 30 days after index MI), and prior AF. Multivariate adjustment of median costs accounted for right‐censoring in costs.ResultsThe final study cohort had 1389 patients, with 989 in no AF, 163 in new‐onset AF, and 237 in prior AF categories. Median follow‐up times were 3.98, 3.23, and 2.55 years, respectively. Mean age at index was 67 years, with significantly younger patients in the no AF group (64 years vs 76 and 77 years, respectively; P < 0.001). New‐onset and prior AF patients had more comorbid conditions (hypertension, heart failure, and chronic obstructive pulmonary disease). After accounting for differences in baseline characteristics, we found adjusted median (95% confidence interval) costs of $73 000 ($69 000‐$76 000) for no AF; $85 000 ($81 000‐$89 000) for new‐onset AF; and $97 000 ($94 000‐$100 000) for prior AF. Inpatient costs composed the largest share of total median costs (no AF, 82%; new‐onset AF, 84%; prior AF, 83%).ConclusionsAtrial fibrillation frequently coexists with MI and imposes incremental costs, mainly attributable to inpatient care. Timing of AF matters, as prior AF was found to be associated with higher costs than new‐onset AF.