Drivers of Hospitalization for Patients With AF
The overall ORBIT-AF population included 10,132 patients from 174 sites. After excluding 648 patients who did not have 6- or 12-month follow-up, this yielded a study population of 9,484 patients from 174 sites, enrolled from June 29, 2010, to August 9, 2011. During the follow-up period, these patients experienced a total of 4,548 hospitalizations; 69% had no hospitalization, 21% had exactly 1 hospitalization, and 10.4% had 2 or more hospitalizations during the follow-up period (Figure 1). Overall, 2,963 (31%) patients had at least 1 hospitalization during follow-up; baseline characteristics, stratified by occurrence of any hospitalization, are shown in Table I . Patients hospitalized were slightly older (median 76 vs 75 years, P < .0001), tended to be female (44% vs 42%, P = .046), and were more likely to have a government payer (Medicare/Medicaid 73% vs 69%, P = .0002). Overall, patients who experienced hospitalization were more likely to have significant cardiovascular risk factors and noncardiovascular disease or comorbidities. Compared with patients not hospitalized, those hospitalized were more likely to have concomitant cardiovascular disease, including peripheral vascular disease, coronary artery disease, and cerebrovascular disease (P < .0001 for each).
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Figure 1.
Distribution of number of hospitalizations at 1 year of follow-up.
Type of AF at baseline was not associated with hospitalization; however, patients hospitalized had worse European Heart Rhythm Association (EHRA) symptom scores (18% with severe symptoms vs 13%, P < .0001) and higher CHADS2 scores (mean 2.5 vs 2.2, P < .0001). Use of any oral anticoagulant (78% vs 76%, 0.14) was not different across patients based on hospitalization. Patients who experienced hospitalization were more likely to have warfarin monitored by an anticoagulation clinic (35% vs 30%, P = .0001), had their INR tested more frequently (4.7% monitored weekly vs 3.3%, P < .0001), and had lower TTR (54% vs 65%, P < .0001). Use of both aspirin (47% vs 43%, P = .001) and clopidogrel (9.5% vs 6.1%, P < .0001) was more common in patients with at least 1 hospitalization. Characteristics of patients hospitalized multiple times during the follow-up period, compared with those hospitalized none or one time, are shown in the Supplementary Material ( Table S1 ).
Of 4,548 hospitalizations, 2,242 (49%) were for cardiovascular reasons, 345 (7.6%) were for bleeding, and 1,961 (43%) were for other reasons. Cause-specific hospitalization rates, by subgroup, are shown in Figure 2. Patients with heart failure had the highest rates of hospitalization, for any cause, and proportions of cardiovascular, bleeding, and other hospitalizations appeared stable across subgroups.
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Figure 2.
Rates of cause-specific hospitalization in patients with AF, by subgroup. P values presented are for the comparison of first all-cause hospitalization between the subgroups. HF, heart failure.
Patients with any hospitalization during follow-up died at a rate of 10.81 events per 100 patient-years vs 1.92 deaths per 100 patient-years for patients without any hospitalization during follow-up. Mortality was highest among patients hospitalized multiple times during follow-up (14.8 per 100 patient-years), compared with 8.9 per 100 patient-years in patients hospitalized once during follow-up.
All-cause first hospitalization occurred in at a rate of 38.8 per 100 patient-years (cardiovascular: 20.1 per 100 patient-years; bleeding: 3.3 per 100 patient years; other: 17.5 per 100 patient-years). Kaplan-Meier curves for cause-specific first hospitalization, calculated independently, are shown in Figure 3.
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Figure 3.
Kaplan-Meier rates of first hospitalization, by cause.
In multivariable analysis, patients with significant heart failure at baseline (New York Heart Association [NYHA] class II or III/IV) had the highest hazards of all-cause (adjusted HR 1.57 for NYHA III/IV, 95% CI 1.38–1.78) and cardiovascular (adjusted HR 1.72, 95% CI 1.46–2.04) hospitalization. Severe symptoms of AF by EHRA classification (those affecting daily activities) were also significantly predictive of all-cause (adjusted HR 1.37 EHRA severe symptoms, 95% CI 1.21–1.55), as was elevated heart rate at baseline (adjusted HR 1.11 per every 10-beats/min increase over 66, 95% CI 1.07–1.16). In addition, several measures of AF chronicity and severity (eg, left-atrial size, AF type), as well as several cardiovascular and noncardiovascular comorbidities, were all also significantly associated with hospitalization. Complete model details for first all-cause hospitalization are shown in Table II . In a model of first cardiovascular hospitalization, EHRA symptoms and heart rate persisted as significant factors (see Table S1 , Table S2 , and Table S3 ).
We subsequently modeled predictors of first all-cause and cardiovascular hospitalization after excluding all patients with heart failure (n = 6,369 without heart failure; 67%). For both all-cause and cardiovascular hospitalization, the major predictors were EHRA severe symptoms (adjusted HR for all-cause hospitalization 1.42, 95% CI 1.19–1.69; adjusted HR for cardiovascular hospitalization 1.96, 95% CI 1.57–2.45) and increasing heart rate (adjusted HR per 10 beats/min for all-cause hospitalization 1.11, 95% CI 1.05–1.17; adjusted HR per 10 beats/min for cardiovascular hospitalization 1.17, 95% CI 1.10–1.25). Concomitant disease also contributed to risk of hospitalization among patients with AF without heart failure (see Table S1 , Table S2 , and Table S3 ).
Results
The overall ORBIT-AF population included 10,132 patients from 174 sites. After excluding 648 patients who did not have 6- or 12-month follow-up, this yielded a study population of 9,484 patients from 174 sites, enrolled from June 29, 2010, to August 9, 2011. During the follow-up period, these patients experienced a total of 4,548 hospitalizations; 69% had no hospitalization, 21% had exactly 1 hospitalization, and 10.4% had 2 or more hospitalizations during the follow-up period (Figure 1). Overall, 2,963 (31%) patients had at least 1 hospitalization during follow-up; baseline characteristics, stratified by occurrence of any hospitalization, are shown in Table I . Patients hospitalized were slightly older (median 76 vs 75 years, P < .0001), tended to be female (44% vs 42%, P = .046), and were more likely to have a government payer (Medicare/Medicaid 73% vs 69%, P = .0002). Overall, patients who experienced hospitalization were more likely to have significant cardiovascular risk factors and noncardiovascular disease or comorbidities. Compared with patients not hospitalized, those hospitalized were more likely to have concomitant cardiovascular disease, including peripheral vascular disease, coronary artery disease, and cerebrovascular disease (P < .0001 for each).
(Enlarge Image)
Figure 1.
Distribution of number of hospitalizations at 1 year of follow-up.
Type of AF at baseline was not associated with hospitalization; however, patients hospitalized had worse European Heart Rhythm Association (EHRA) symptom scores (18% with severe symptoms vs 13%, P < .0001) and higher CHADS2 scores (mean 2.5 vs 2.2, P < .0001). Use of any oral anticoagulant (78% vs 76%, 0.14) was not different across patients based on hospitalization. Patients who experienced hospitalization were more likely to have warfarin monitored by an anticoagulation clinic (35% vs 30%, P = .0001), had their INR tested more frequently (4.7% monitored weekly vs 3.3%, P < .0001), and had lower TTR (54% vs 65%, P < .0001). Use of both aspirin (47% vs 43%, P = .001) and clopidogrel (9.5% vs 6.1%, P < .0001) was more common in patients with at least 1 hospitalization. Characteristics of patients hospitalized multiple times during the follow-up period, compared with those hospitalized none or one time, are shown in the Supplementary Material ( Table S1 ).
Causes of Hospitalization
Of 4,548 hospitalizations, 2,242 (49%) were for cardiovascular reasons, 345 (7.6%) were for bleeding, and 1,961 (43%) were for other reasons. Cause-specific hospitalization rates, by subgroup, are shown in Figure 2. Patients with heart failure had the highest rates of hospitalization, for any cause, and proportions of cardiovascular, bleeding, and other hospitalizations appeared stable across subgroups.
(Enlarge Image)
Figure 2.
Rates of cause-specific hospitalization in patients with AF, by subgroup. P values presented are for the comparison of first all-cause hospitalization between the subgroups. HF, heart failure.
Mortality
Patients with any hospitalization during follow-up died at a rate of 10.81 events per 100 patient-years vs 1.92 deaths per 100 patient-years for patients without any hospitalization during follow-up. Mortality was highest among patients hospitalized multiple times during follow-up (14.8 per 100 patient-years), compared with 8.9 per 100 patient-years in patients hospitalized once during follow-up.
Predictors of First Incident Hospitalization
All-cause first hospitalization occurred in at a rate of 38.8 per 100 patient-years (cardiovascular: 20.1 per 100 patient-years; bleeding: 3.3 per 100 patient years; other: 17.5 per 100 patient-years). Kaplan-Meier curves for cause-specific first hospitalization, calculated independently, are shown in Figure 3.
(Enlarge Image)
Figure 3.
Kaplan-Meier rates of first hospitalization, by cause.
In multivariable analysis, patients with significant heart failure at baseline (New York Heart Association [NYHA] class II or III/IV) had the highest hazards of all-cause (adjusted HR 1.57 for NYHA III/IV, 95% CI 1.38–1.78) and cardiovascular (adjusted HR 1.72, 95% CI 1.46–2.04) hospitalization. Severe symptoms of AF by EHRA classification (those affecting daily activities) were also significantly predictive of all-cause (adjusted HR 1.37 EHRA severe symptoms, 95% CI 1.21–1.55), as was elevated heart rate at baseline (adjusted HR 1.11 per every 10-beats/min increase over 66, 95% CI 1.07–1.16). In addition, several measures of AF chronicity and severity (eg, left-atrial size, AF type), as well as several cardiovascular and noncardiovascular comorbidities, were all also significantly associated with hospitalization. Complete model details for first all-cause hospitalization are shown in Table II . In a model of first cardiovascular hospitalization, EHRA symptoms and heart rate persisted as significant factors (see Table S1 , Table S2 , and Table S3 ).
We subsequently modeled predictors of first all-cause and cardiovascular hospitalization after excluding all patients with heart failure (n = 6,369 without heart failure; 67%). For both all-cause and cardiovascular hospitalization, the major predictors were EHRA severe symptoms (adjusted HR for all-cause hospitalization 1.42, 95% CI 1.19–1.69; adjusted HR for cardiovascular hospitalization 1.96, 95% CI 1.57–2.45) and increasing heart rate (adjusted HR per 10 beats/min for all-cause hospitalization 1.11, 95% CI 1.05–1.17; adjusted HR per 10 beats/min for cardiovascular hospitalization 1.17, 95% CI 1.10–1.25). Concomitant disease also contributed to risk of hospitalization among patients with AF without heart failure (see Table S1 , Table S2 , and Table S3 ).