Atrial fibrillation (AF) is associated with stroke and death. We sought to determine whether there are any racial differences in the outcomes of death and stroke in patients with AF. We used Medicare administrative data from January 1, 2010, to December 31, 2011, to identify 517,941 patients with newly diagnosed AF. Of these, 452,986 patients (87%) were non-Hispanic white, 36,425 (7%) were black, and 28,530 (6%) were Hispanic. The association between race and outcomes of death and stroke were measured using Cox proportional hazard models. Over a median follow-up period of 20.3 months, blacks had a significantly higher hazard of death (hazard ratio [HR] = 1.46; 95% confidence interval [CI] 1.43 to 1.48; p <0.001) and stroke (HR = 1.66; 95% CI 1.57 to 1.75; p <0.001), compared with white patients. After controlling for pre-existing co-morbidities, the higher hazard of death in blacks was eliminated (HR 0.95; 95% CI 0.93 to 0.96; p <0.001) and the relative hazard of stroke was reduced (HR = 1.46; 95% CI 1.38 to 1.55; p <0.001). Similarly, Hispanics had a higher risk of death (HR = 1.11; 95% CI 1.09 to 1.14; p <0.001) and stroke (HR = 1.21; 95% CI 1.13 to 1.29; p <0.001) compared with whites. The relative hazard of death was lower in Hispanics (HR 0.82; 95% CI 0.80 to 0.84; p <0.001) compared with whites, after controlling for pre-existing co-morbidities, and the relative hazard of stroke was also attenuated (HR = 1.11; 95% CI 1.03 to 1.18; p <0.001). In conclusion, in patients >65 years with newly diagnosed AF, the risks of death and stroke are higher in blacks and Hispanics compared with whites. The increased risk was eliminated or significantly reduced after adjusting for pre-existing co-morbidities. AF may be a marker for underlying co-morbidities in black and Hispanic patients who may be at a higher mortality risk.
Several studies have shown that despite having higher risk factors for developing atrial fibrillation (AF), the risk of AF is lower in black Americans compared with white Americans. A recent study found similar results in Hispanics. However, less is known about differences in AF-related outcomes by race and ethnicity. Race-based differences in outcomes have been reported in other cardiovascular conditions, such as acute myocardial infarction (AMI) and cardiac arrest, where blacks had worse outcomes than the whites. Although both AMI and cardiac arrest are acute conditions, AF is a chronic condition and racial differences in outcomes with AF have not been adequately studied. To address this gap in knowledge, we used Medicare data to examine whether the risk of death and stroke in patients with newly diagnosed AF differed by a patient’s race.
Methods
We used data obtained from the Centers for Medicare and Medicaid (CMS) for years 2009 through 2012, including (1) Beneficiary Summary File Base and Chronic Condition segments, (2) Inpatient (part A) and Carrier (part B) Standard Analytic Files, and (3) Pharmacy Drug Event (part D). Patients were included in the study if they had a new AF diagnosis during the period January 2010 to December 31, 2011. New AF was defined based on previously published algorithms (i.e., 1 inpatient claim or 2 outpatient claims within a year with International Classification of Diseases, Ninth Revision, Clinically Modification ( ICD-9-CM ) code 427.31 as primary or first secondary diagnosis, with no previous AF diagnoses during the previous 12 months). Patients were excluded if they were <66 years at the time of diagnosis (to ensure at least 12 months of Medicare eligibility before diagnosis), were enrolled in a Medicare managed care during the observation period, or were not enrolled in a Part D drug prescription plan at the time of AF diagnosis.
Patient race or ethnicity was determined using the race code developed by the Research Triangle Institute (RTI) that is available on the CMS Beneficiary Summary File. The RTI race code is an enhanced race/ethnicity designation based on first and last name algorithms. The RTI race code agrees excellently with self-reported race, with kappa coefficients ≥0.80 for Hispanic beneficiaries and ≥0.90 for black beneficiaries.
Additional patient characteristics were identified in the CMS enrollment and encounter data. Dual enrollment in Medicaid at the time of AF diagnosis was identified from the CMS Beneficiary Enrollment Summary. Co-morbid conditions were identified in inpatient and outpatient claims during the 12 months before the first AF diagnosis date and were defined using algorithms originally developed by Elixhauser et al. Previous cerebrovascular events were identified using previously published algorithms, as were previous bleeding episodes.
Risk scoring systems were used to assess the risk of stroke and bleeding. To assess the risk of stroke, the CHA 2 DS 2 -VASc risk scores were calculated based on a point system reflecting the presence of congestive heart failure (1 point), hypertension (1 point), age more than or equal to 75 years (2 points), diabetes (1 point), previous stroke (2 points), vascular disease (1 point), age 65 to 74 (1 point), and female gender (1 point). A modified HAS-BLED risk score was also calculated to assess bleeding risk based on the presence of hypertension, previous stroke, advanced age, renal disease, liver disease, and alcohol abuse. Finally, we identified the date of first oral anticoagulant prescription fill after initial AF diagnosis in part D event data to control for potential confounding because of differences in the use of oral anticoagulants by race.
Our primary outcome was death through December 31, 2012. The secondary outcome was stroke, as identified on inpatient Standard Analytic Files claims for years 2010 to 2012 and included acute hospitalizations admitted as emergent or urgent with a primary diagnosis of cerebral infarction ( ICD-9-CM codes 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, and 434.91). Dates of death were identified on the Beneficiary Summary File. For each patient, the date of the first occurrence of each outcome after AF diagnosis was identified. Patients who did not experience the outcome of interest were censored on December 31, 2012.
Data analysis encompassed bivariable and multivariable methods. First, characteristics of patients as of the date of first AF diagnosis were compared by race and ethnicity. Categorical variables (e.g., presence of hypertension) were compared using the chi-square statistic, whereas continuous or interval variables (e.g., age), were compared using analysis of variance. Subsequently, we created for each patient a longitudinal record that included the date of first AF diagnosis, pre-existing patient characteristics and co-morbidities, oral anticoagulant use, and number of days to first stroke and death. Cox regression models were used to evaluate the relative hazard of stroke and death by race. The exponentiated value of the regression coefficients associated with black race or Hispanic ethnicity provides the relative hazard of each outcome in black patients (or Hispanic), relative to non-Hispanic white patients. Initial models included race/ethnicity indicators only, whereas subsequent models controlled for the patient demographic and co-morbid conditions displayed in Table 1 , using a statistical criterion of p <0.05 to identify variables eligible for inclusion in multivariable models. A second set of risk adjustment models were estimated that further controlled for the use of oral anticoagulants after initial AF diagnosis, treating oral anticoagulant use as a time-dependent indicator variable set to 1 after the first prescription fill. We also examined the interaction between race or ethnicity and gender to determine whether racial differences are consistent for men and women. The final risk adjustment models for stroke and death are shown in the Supplementary Table 1 . Finally, we conducted sensitivity analyses to examine the consistency of our findings across patient strata defined by age category (age 66 to74, 75 to 84, and ≥85 years), stroke risk (i.e., CHA 2 DS 2 -VASc score 0 to 4, 5 to 6, and ≥7), and setting of initial AF diagnosis (inpatient vs outpatient).
| Whites (N=452,986) | Blacks (N=36,425) | Hispanics (N= 28,530) | |
|---|---|---|---|
| Variables | |||
| Age (years), mean (SD) | 79.2 (8.07) | 78.8 (8.3) | 79.1 (7.83) |
| Age Category (years): | |||
| 66 to 74 | 149,339 (43.5%) | 13,134 (46.8%) | 9,202 (41.4%) |
| 75 to 84 | 177,038 (51.6%) | 13,694 (48.8%) | 11,953 (53.7%) |
| ≥ 85 years | 16,654 (4.9%) | 1,229 (4.4%) | 1,087 (4.9%) |
| Males | 185,935 (41.1%) | 12,476 (34.3%) | 11,415 (40%) |
| Dual enrollment in Medicaid | 114,966 (25.4%) | 25,543 (70%) | 21,779 (76%) |
| Hypertension | 37,097 (82%) | 33,546 (92%) | 25,128 (88%) |
| Heart failure | 164,571 (36.3%) | 19,349 (53.1%) | 13,436 (47.1%) |
| Pulmonary circulatory disease | 53342 (11.8%) | 6638 (18.2%) | 3531 (12.4%) |
| Prior stroke | 74,025(16.3%) | 10,360(28.4%) | 6490 (22.7%) |
| Prior myocardial infarction | 60,192 (13%) | 5,825 (16%) | 6,490 (22.7%) |
| Prior bleeding | 120,371 (27%) | 12,229 (34%) | 9,130 (32%) |
| Malignancy | 81,376 (18%) | 6,473 (17.8%) | 4,121 (14.4%) |
| Renal failure | 85,902 (19%) | 13,448 (37%) | 7,962 (28%) |
| Diabetes Mellitus | 149,114 (33%) | 18,858 (52%) | 15,600 (55%) |
| Dementia | 40,378 (9%) | 6,379 (18%) | 3,745 (13%) |
| Obesity | 35,592 (7.9%) | 4,439 (12.2%) | 3,202 (11.2%) |
| HAS-BLED score, mean (SD) | 2.55 (1.02) | 3.03 (1.12) | 2.89 (1.13) |
| CHA 2 DS 2 -VASc score, mean (SD) | 4.75 (1.58) | 5.49 (1.58) | 5.34 (1.58) |
| CHA 2 DS 2 –VASc score | |||
| 0-2 | 35,665 (7.9%) | 1,085 (3.0%) | 1,168 (4.1%) |
| 3 | 60,245 (13.3%) | 2,650 (7.3%) | 2,277 (8.0%) |
| 4 | 98,820 (21.8%) | 5,667 (15.6%) | 4,620 (16.2%) |
| 5 | 116,117 (25.6%) | 8,910 (24.5%) | 7,110 (24.9%) |
| 6 | 84,570 (18.7%) | 8,904 (14.4%) | 7,044 (24.7%) |
| 7 or more | 57,569 (12.7%) | 9,209 (25.3%) | 6,311 (22.1%) |
∗ p< 0.001 for all comparisons based on Chi-square test for categorical variables and analysis for variance for mean CHA 2 DS 2 -VASc, HAS-BLED, and patient age.
Results
A total of 517,941 non-Hispanic white, non-Hispanic black, or Hispanic patients met criteria for newly diagnosed AF and were included in the study. Of these, 452,986 (87%) were whites, 36,425 (7%) were blacks, and 28,530 (6%) were Hispanics. Patient baseline demographics by race are presented in Table 1 . Although the mean age was similar across groups, the prevalence of several co-morbid conditions was significantly higher for blacks and Hispanics compared with whites. The mean CHA 2 DS 2 -VASc score was higher in blacks and Hispanics, compared with whites, indicating higher risk of stroke. Black and Hispanic patients were also significantly more likely to be dually enrolled in Medicaid compared with white patients. White patients were more likely to receive oral anticoagulants within 90 days of the initial AF diagnosis, compared with black or Hispanic patients (40% vs 35% and 34%, respectively).
Over a median follow-up period of 20.3 months per patient (interquartile range 13.1 to 27.4 months), 136,271 whites (30%), 14,850 blacks (41%), and 9,343 Hispanics (33%) died. Overall, 12,337 whites (2.7%), 1,504 blacks (4.1%), and 910 Hispanics (3.2%) experienced stroke. Table 2 lists unadjusted rates of death and stroke per 100 person-years of follow-up for white, black, and Hispanic patients.
| Events (Total and per 100 person-years) ∗ | |||
|---|---|---|---|
| Whites | Blacks | Hispanics | |
| Death – Number Events | 136,271 | 14,850 | 9,343 |
| – Per 100 Person-years | 18.48 (95% CI, 18.39-18.58) | 27.72 (95% CI, 27.27-28.16) | 20.76 (95% CI, 20.34-21.18) |
| Stroke – Number Events | 12,337 | 1,504 | 910 |
| – Per 100 Person-Years | 1.70 (95% CI, 1.68-1.74) | 2.89 (95% CI, 2.75-3.05) | 2.06 (95% CI, 1.94-2.21) |
∗ Rate calculated as 100*(Number of Events / Total person-years of follow-up). Lower Limit of Confidence Interval calculated as Rate divided by D, and Upper Limit calculated as Rate multiplied by D, where D= exp[1.96*square root of (1/number of events)].
In unadjusted analyses, black patients had a significantly higher hazard of death (hazard ratio [HR] = 1.46; 95% confidence interval [CI] 1.43 to 1.48; p <0.001) and stroke (HR = 1.66; 95% CI 1.57 to 1.75; p <0.001), compared with white patients ( Table 3 ). Hispanic patients also had a higher risk of death (HR = 1.11; 95% CI 1.09 to 1.14; p <0.001) and stroke (HR = 1.21; 95% CI 1.13 to 1.29; p <0.001) compared with white patients.
| Admission for Stroke | |||||
|---|---|---|---|---|---|
| Unadjusted | Risk Adjusted | Risk adjusted plus anticoagulant indicator | |||
| Black vs. White | 1.66 (1.57-1.75; p<.001) | 1.46 (1.39-1.55; p<.001) | 1.44 (1.36-1.52; p<.001) | ||
| Hispanic vs white | 1.21 (1.13-1.29; p<.001) | 1.11 (1.03-1.18; p=.003) | 1.08 (1.01-1.16; p=.02) | ||
| Death | |||||
| Unadjusted | Risk Adjusted | Risk adjusted plus anticoagulant indicator | |||
| Black vs. White | 1.46 (1.43-1.48; p<.001) | 0.95 (0.93-0.96; p<.001) | 0.94 (0.92-0.96; p<.001) | ||
| Hispanic vs white | 1.11 (1.09-1.14; p<.001) | 0.82 (0.80-0.84; p<.001) | 0.81 (0.79-0.83; p<.001) | ||
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