Rate or Rhythm Control in Older Atrial Fibrillation Patients: Risk of Fall-Related Injuries and Syncope.

OBJECTIVES: Management of atrial fibrillation (AF) with rate and/or rhythm control could lead to fall-related injuries and syncope, especially in the older AF population. We aimed to determine the association of rate and/or rhythm control with fall-related injuries and syncope in a real-world older AF cohort. DESIGN: A retrospective cohort study. SETTING: Danish nationwide administrative registries from 2000 to 2015. PARTICIPANTS: A total of 100 935 patients with AF aged 65 years or older claiming prescription of rate-lowering drugs (RLDs) and/or anti-arrhythmic drugs (AADs) were included. We compared the use of rate-lowering monotherapy with rate-lowering dual therapy, AAD monotherapy, and AAD combined with rate-lowering therapy. MEASUREMENTS: Outcomes were fall-related injuries and syncope as a composite end point (primary) or separate end point (secondary). RESULTS: In this population, the median age was 78 years (interquartile range [IQR] = 72-84 y), and 53 481 (53.0%) were women. During a median follow-up of 2.1 years (IQR = 1.0-5.1), 17 132 (17.0%) experienced a fall-related injury, 5745 (5.7%) had a syncope, and 21 093 (20.9%) experienced either. Compared with rate-lowering monotherapy, AADs were associated with a higher risk of fall-related injuries and syncope. The incidence rate ratio (IRR) for the composite end point was 1.29 (95% confidence interval [CI]: 1.17-1.43) for AAD monotherapy and 1.46 [95% CI = 1.34-1.58] for AAD combined with rate-lowering therapy. When stratifying by individual drugs, amiodarone significantly increased the risk of fall-related injuries and syncope (IRR = 1.40 [1.26-1.55]). Compared with more than 180 days of rate-lowering monotherapy, a higher risk of all outcomes was seen in the first 90 days of any treatment; however, the greatest risk was in the first 14 days for those treated with AADs. CONCLUSION: In AF patients aged 65 years and older, AAD use was associated with a higher risk of fall-related injuries and syncope, and the risk was highest within the first 14 days for those treated with AADs. Only amiodarone use was associated with a higher risk. J Am Geriatr Soc 67:2023-2030, 2019.

Risk of post-discharge fall-related injuries among adult patients with syncope: A nationwide cohort study.

BACKGROUND: Syncope could be related to high risk of falls and injury in adults, but documentation is sparse. We examined the association between syncope and subsequent fall-related injuries in a nationwide cohort. METHODS: By cross-linkage of nationwide registers, all residents ≥18 years with a first-time diagnosis of syncope were identified between 1997-2012. Syncope patients were matched 1:1 with individuals from the general population. The absolute one-year risk of fall-related injuries, defined as fractures and traumatic head injuries requiring hospitalization, was calculated using Aalen-Johansen estimator. Ratios of the absolute one-year risk of fall-related injuries (ARR) were assessed by absolute risk regression analysis. RESULTS: We identified 125,763 patients with syncope: median age 65 years (interquartile range 46-78). At one year, follow-up was complete for 99.8% where a total of 8394 (6.7%) patients sustained a fall-related injury requiring hospitalization, of which 1606 (19.1%) suffered hip fracture. In the reference group, 4049 (3.2%) persons had a fall-related injury. The one-year ARR of a fall-related injury was 1.79 (95% confidence interval 1.72-1.87, P<0.001) in patients with syncope compared with the reference group; however, increased ARR was not exclusively in older patients. Factors independently associated with increased ARR of fall-related injuries in the syncope population were: injury in past 12 months, 2.39 (2.26-2.53, P<0.001), injury in relation to the syncope episode, 1.62 (1.49-1.77, P<0.001), and depression, 1.37 (1.30-1.45, P<0.001). CONCLUSION: Patients with syncope were at 80% increased risk of severe fall-related injuries within the year following discharge. Notably, increased risk was not exclusively in older patients.

Nursing home admission after myocardial infarction in the elderly: A nationwide cohort study.

BACKGROUND: Data on nursing home admission after myocardial infarction (MI) in the elderly are scarce. We investigated nursing home admission within 6 months and 2 years after MI including predictors for nursing home admission in a nationwide cohort of elderly patients. METHODS: Using Danish nationwide registries, we identified all subjects 65 years or older residing at home who were discharged following first-time MI in the period 2008-2015. We determined sex- and age-stratified incidence rates per 1000 person years (IRs) and incidence rate ratios (IRRs) of nursing home admissions using Poisson regression models compared to the Danish population 65 years or older with no prior MI. Poisson regression models were also applied to identify predictors of nursing home admission. RESULTS: The 26,539 patients who were discharged after MI had a median age of 76 (quartile 1-quartile 3: 70-83) years. The IRs of nursing home admission after MI increased with increasing age and for 80-84-year-old women IRs after 6 months and 2 years were 113.9 and 62.9, respectively, compared to 29.4 for women of the same age with no prior MI. The IRs for 80-84-year-old men after MI were 56.0 and 36.2, respectively, compared to 24.3 for men of the same age with no prior MI. In adjusted analyses the 6 months and 2 years IRRs for 80-84-year-old subjects were 2.56 (95% CI 2.11-3.10) and 1.41 (95% CI 1.22-1.65) for women and 1.74 (95% CI 1.34-2.25) and 1.05 (95% CI 0.88-1.26) for men, respectively. Predictors were advanced age, dementia, home care, Parkinson's disease, cerebrovascular disease, living alone, depression, and arrhythmia. CONCLUSION: In elderly patients discharged following first-time MI, the risk of subsequent nursing home admission within 6 months was 2-fold higher compared to an age-stratified population with no prior MI. After 2 years this risk remained higher in women.

Prevalence of Pulmonary Embolism in Patients With Syncope.

Importance: Sparse data and conflicting evidence exist on the prevalence of pulmonary embolism (PE) in patients with syncope. Objective: To estimate the prevalence of PE among patients presenting to the emergency department (ED) for evaluation of syncope. Design, Setting, and Participants: This retrospective, observational study analyzed longitudinal administrative data from 5 databases in 4 different countries (Canada, Denmark, Italy, and the United States). Data from all adult patients (aged ≥18 years) who presented to the ED were screened to identify those with syncope codes at discharge. Data were collected from January 1, 2000, through September 30, 2016. Main Outcomes and Measures: The prevalence of PE at ED and hospital discharge, identified using codes from the International Classification of Diseases, was considered the primary outcome. Two sensitivity analyses considering prevalence of PE at 90 days of follow-up and prevalence of venous thromboembolism were performed. Results: A total of 1 671 944 unselected adults who presented to the ED for syncope were included. The prevalence of PE, according to administrative data, ranged from 0.06% (95% CI, 0.05%-0.06%) to 0.55% (95% CI, 0.50%-0.61%) for all patients and from 0.15% (95% CI, 0.14%-0.16%) to 2.10% (95% CI, 1.84%-2.39%) for hospitalized patients. The prevalence of PE at 90 days of follow-up ranged from 0.14% (95% CI, 0.13%-0.14%) to 0.83% (95% CI, 0.80%-0.86%) for all patients and from 0.35% (95% CI, 0.34%-0.37%) to 2.63% (95% CI, 2.34%-2.95%) for hospitalized patients. Finally, the prevalence of venous thromboembolism at 90 days ranged from 0.30% (95% CI, 0.29%-0.31%) to 1.37% (95% CI, 1.33%-1.41%) for all patients and from 0.75% (95% CI, 0.73%-0.78%) to 3.86% (95% CI, 3.51%-4.24%) for hospitalized patients. Conclusions and Relevance: Pulmonary embolism was rarely identified in patients with syncope. Although PE should be considered in every patient, not all patients should undergo evaluation for PE.

Employment status at time of first hospitalization for heart failure is associated with a higher risk of death and rehospitalization for heart failure.

AIMS: Employment status at time of first heart failure (HF) hospitalization may be an indicator of both self-perceived and objective health status. In this study, we examined the association between employment status and the risk of all-cause mortality and recurrent HF hospitalization in a nationwide cohort of patients with HF. METHODS AND RESULTS: We identified all patients of working age (18-60 years) with a first HF hospitalization in the period 1997-2015 in Denmark, categorized according to whether or not they were part of the workforce at time of the index admission. The primary outcome was death from any cause and the secondary outcome was readmission for HF. Cumulative incidence curves, binomial regression and Cox regression models were used to assess outcomes. Of 25 571 patients with a first hospitalization for HF, 15 428 (60%) were part of the workforce at baseline. Patients in the workforce were significantly younger (53 vs. 55 years) more likely to be male (75% vs 64%) and less likely to have diabetes (13% vs 22%) and chronic obstructive pulmonary disease (5% vs 10%) (all P < 0.0001). Not being part of the workforce was associated with a significantly higher risk of death [hazard ratio (HR) 1.59; 95% confidence interval (CI) 1.50-1.68] and rehospitalization for HF (HR 1.09; 95% CI 1.05-1.14), in analyses adjusted for age, sex, co-morbidities, education level, calendar time, and duration of first HF hospitalization. CONCLUSION: Not being part of the workforce at time of first HF hospitalization was independently associated with increased mortality and recurrent HF hospitalization.

Return to Work and Risk of Subsequent Detachment From Employment After Myocardial Infarction: Insights From Danish Nationwide Registries.

BACKGROUND: Limited data are available on return to work and subsequent detachment from employment after admission for myocardial infarction (MI). METHODS AND RESULTS: Using individual-level linkage of data from nationwide registries, we identified patients of working age (30-65 years) discharged after first-time MI in the period 1997 to 2012, who were employed before admission. To assess the cumulative incidence of return to work and detachment from employment, the Aalen Johansen estimator was used. Incidences were compared with population controls matched on age and sex. Logistic regression was applied to estimate odds ratios for associations between detachment from employment and age, sex, comorbidities, income, and education level. Of 39 296 patients of working age discharged after first-time MI, 22 394 (56.9%) were employed before admission. Within 1 year 91.1% (95% confidence interval [CI], 90.7%-91.5%) of subjects had returned to work, but 1 year after their return 24.2% (95% CI, 23.6%-24.8%) were detached from employment and received social benefits. Detachment rates were highest in patients aged 60 to 65 and 30 to 39 years, and significantly higher in patients with MI compared with population controls. Predictors of detachment were heart failure (odds ratio 1.20 [95% CI, 1.08-1.34]), diabetes mellitus (odds ratio 1.13 [95% CI, 1.01-1.25]), and depression (odds ratio 1.77 [95% CI, 1.55-2.01]). High education level and high income favored continued employment. CONCLUSIONS: Despite that most patients returned to work after first-time MI, about 1 in 4 was detached from employment after 1 year. Several factors including age and lower socioeconomic status were associated with risk of detachment from employment.

Syncope and Its Impact on Occupational Accidents and Employment: A Danish Nationwide Retrospective Cohort Study.

BACKGROUND: First-time syncopal episodes usually occur in adults of working age, but their impact on occupational safety and employment remains unknown. We examined the associations of syncope with occupational accidents and termination of employment. METHODS AND RESULTS: Through linkage of Danish population-based registers, we included all residents 18 to 64 years from 2008 to 2012. Among 3 410 148 eligible individuals, 21 729 with a first-time diagnosis of syncope were identified, with a median age 48.4 years (first to third quartiles, 33.0-59.5), and 10 757 (49.5%) employed at time of the syncope event. Over a median follow-up of 3.2 years (first to third quartiles, 2.0-4.5), 622 people with syncope had an occupational accident requiring hospitalization (2.1/100 person-years). In multiple Poisson regression analysis, the incidence rate ratio in the employed syncope population was higher than in the employed general population (1.44; 95% confidence interval [CI], 1.33-1.55) and more pronounced in people with recurrences (2.02; 95% CI, 1.47-2.78). The 2-year risk of termination of employment was 31.3% (95% CI, 30.4%-32.3%), which was twice the risk of the reference population (15.2%; 95% CI, 14.7%-15.7%), using the Aalen-Johansen estimator. Factors associated with termination of employment were age <40 years (incidence rate ratio, 1.48; 95% CI, 1.37-1.59), cardiovascular disease (1.20; 95% CI, 1.06-1.36), depression (1.72; 95% CI, 1.55-1.90), and low educational level (2.61; 95% CI, 2.34-2.91). CONCLUSIONS: In this nationwide cohort, syncope was associated with a 1.4-fold higher risk of occupational accidents and a 2-fold higher risk of termination of employment compared with the employed general population.

Syncope and Motor Vehicle Crash Risk: A Danish Nationwide Study.

IMPORTANCE: Syncope may have serious consequences for traffic safety. Current clinical guideline recommendations on driving following syncope are primarily based on expert consensus. OBJECTIVE: To identify whether there is excess risk of motor vehicle crashes among patients with syncope compared with the general population. DESIGN, SETTING, AND PARTICIPANTS: Danish nationwide cohort study from January 1, 2008, to December 31, 2012. Through individual-level linkage of nationwide administrative registers, all Danish residents 18 years or older were identified. Of 4 265 301 eligible Danish residents, we identified 41 039 individuals with a first-time diagnosis of syncope from emergency department or hospital. MAIN OUTCOMES AND MEASURES: Rate of motor vehicle crashes (including nonfatal and fatal crashes), based on multivariate Poisson regression models, using the total Danish population as reference. RESULTS: The 41 039 patients with syncope had a median age of 66 years (interquartile range [IQR], 47-78 years); 51.0% were women; and 34.8% had cardiovascular disease. Through a median follow-up of 2.0 years (IQR, 0.8-3.3 years), 1791 patients with syncope (4.4%) had a motor vehicle crash, 78.1% of which led to injury (n = 1398) and 0.3% to death (n = 6). The crude incidence rate of motor vehicle crashes was almost doubled among patients with syncope (20.6 per 1000 person-years; 95% CI, 19.7-21.6) compared with the general population (12.1; 95% CI, 12.0-12.1), with a rate ratio (RR) of 1.83 (95% CI, 1.74-1.91) after adjustment for age, sex, socioeconomic position, and relevant comorbidities and pharmacotherapy. Men had a relatively higher rate of motor vehicle crashes (RR, 1.91; 95% CI, 1.79-2.03) than women (RR, 1.74; 95% CI, 1.63-1.87). The excess risk of motor vehicle crashes persisted throughout the follow-up period. The 5-year crash risk following syncope was 8.2% (95% CI, 7.5%-8.8%) among the population aged 18 to 69 years compared with 5.1% (95% CI, 4.7%-5.4%) in the general population. CONCLUSIONS AND RELEVANCE: Prior hospitalization for syncope was associated with increased risk of motor vehicle crashes throughout the follow-up period. This study suggests that syncope should be considered as one of several factors in a broad assessment of fitness to drive.

Comparison of antiplatelet regimens in secondary stroke prevention: a nationwide cohort study.

BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent stroke associated with these three treatments. METHODS: Patients who were discharged with first-time ischemic stroke from 2007-2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus the combination of acetylsalicylic acid and dipyridamole were 1.02 (95% confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95% CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95% CI: 1.31-1.67) for stroke and 1.47 (95% CI: 1.18-1.82) for bleeding. Clopidogrel versus acetylsalicylic acid yielded HRs of 0.69 (95% CI: 0.59-0.81) and 0.72 (95% CI: 0.55-0.96) for stroke and bleeding, respectively. The 1-year predicted risks associated with acetylsalicylic acid, the combination of acetylsalicylic acid and dipyridamole, and clopidogrel were 11.1 (95% CI: 10.2-12.2), 7.7 (95% CI: 7.3-8.3), and 8.0 (95% CI: 6.9-8.7) for ischemic stroke, respectively; while, the risks for bleeding were 3.4 (95% CI: 2.8-3.9), 2.4 (95% CI: 2.1-2.7), and 2.4 (95% CI: 1.9-2.9), respectively. CONCLUSION: Clopidogrel and the combination of acetylsalicylic acid and dipyridamole were associated with similar risks for recurrent ischemic stroke and bleeding; whereas acetylsalicylic acid was associated with higher risks for both ischemic stroke and bleeding. The latter finding may partially be explained by selection bias.

Incidence and influence of hospitalization for recurrent syncope and its effect on short- and long-term all-cause and cardiovascular mortality.

Recurrence of syncope is a common event, but the influence of recurrent syncope on the risk of death has not previously been investigated on a large scale. We examined the prognostic impact of recurrent syncope in a nationwide cohort of patients with syncope. All patients (n = 70,819) hospitalized from 2001 to 2009 in Denmark with a first-time diagnosis of syncope aged from 15 to 90 years were identified from national registries. Recurrence of syncope was incorporated as a time-dependent variable in multivariable-adjusted Cox models on the outcomes of 30-day, 1-year, and long-term all-cause mortality and cardiovascular death. During a mean follow-up of 3.9 ± 2.6 years, a total of 11,621 patients (16.4%) had at least 1 hospitalization for recurrent syncope, with a median time to recurrence of 251 days (33 to 364). A total of 14,270 patients died, and 3,204 deaths were preceded by a hospitalization for recurrent syncope. The long-term risk of all-cause death was significantly associated with recurrent syncope (hazard ratio 2.64, 95% confidence interval 2.54 to 2.75) compared with those with no recurrence. On 1-year mortality, recurrent syncope was associated with a 3.2-fold increase in risk and on 30-day mortality associated with a threefold increase. The increased mortality risk was consistent over age groups 15 to 39, 40 to 59, and 60 to 89 years, and a similar pattern of increase in both long-term and short-term risk of cardiovascular death was evident. In conclusion, recurrent syncope is independently associated with all-cause and cardiovascular mortality across all age groups exhibiting a high prognostic influence. Increased awareness on high short- and long-term risk of adverse events in subjects with recurrent syncope is warranted for future risk stratification.

Comparison of incidence, predictors, and the impact of co-morbidity and polypharmacy on the risk of recurrent syncope in patients <85 versus ≥85 years of age.

Recurrent syncope is a major cause of hospitalizations and may be associated with cardiovascular co-morbidities. Despite this, prognostic factors and the clinical characteristics among patients are not well described. Therefore, we identified and analyzed data on all patients >50 years of age discharged after a first-time episode of syncope in the period 2001 to 2009 through nationwide administrative registries. We identified the clinical characteristics of 5,141 patients ≥85 years of age and 23,454 patients <85 years of age. Multivariate Cox models were used to assess prognostic factors associated with the end point of recurrent syncope according to age. We found that those with syncope and ≥85 years were more often women (65% vs 47%) and generally had a greater prevalence of noncardiovascular co-morbidities, whereas the prevalence of cardiovascular co-morbidities was more heterogeneously distributed across age groups. Overall, significant baseline predictors of recurrent syncope were aortic valve stenosis (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.31 to 1.68), impaired renal function (HR 1.34, 95% CI 1.15 to 1.58), atrioventricular or left bundle branch block (HR 1.32, 95% CI 1.16 to 1.51), male gender (HR 1.18, 95% CI 1.12 to 1.24), chronic obstructive pulmonary disorder (HR 1.10, 95% CI 1.02 to 1.19), heart failure (HR 1.10, 95% CI 1.02 to 1.21), atrial fibrillation (HR = 1.09, 95% CI 1.01 to 1.19), age per 5-year increment (HR 1.09, 95% CI 1.07 to 1.10), and orthostatic medications per increase (HR 1.06, 95% CI 1.03 to 1.09). Atrial fibrillation and impaired renal function both exhibited less prognostic importance for recurrent syncope in the elderly compared with younger population (p for interactions <0.01). In conclusion, predictive factors of recurrent syncope were closely associated with increased cardiovascular risk profile age and gender. The use of multiple orthostatic medications additively increased the risk of recurrences representing a need for strategies to reduce unnecessary polypharmacy.