(Circulation. 2000;102:11.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
From the Division of Research, Kaiser Permanente Medical Care Program (Northern California), Oakland, Calif (A.S.G., K.A.P., J.V.S.); the Department of Epidemiology and Biostatistics, University of California at San Francisco (A.S.G.); and the General Medicine Division, Clinical Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Mass (E.M.H., L.H.B., L.E.H., Y.C., D.E.S.).
Correspondence to Alan S. Go, MD, Division of Research, 3505 Broadway St, Oakland, CA 94611. E-mail axg{at}dor.kaiser.org
| Abstract |
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Methods and ResultsWe used clinical and electrocardiographic
databases to identify 13 559 ambulatory patients with NVAF from July
1996 through December 1997. We compared the proportion of patients
classified as having a low enough stroke risk to receive aspirin using
published criteria from the Atrial Fibrillation Investigators (AFI),
American College of Chest Physicians (ACCP), and the Stroke Prevention
in Atrial Fibrillation Investigators (SPAF). In this cohort, AFI
criteria classified 11% as having a low stroke risk, compared with
23% for ACCP and 29% for SPAF (
range, 0.44 to 0.85). This 2-
to-3-fold increase in low stroke risk patients by ACCP and SPAF
criteria primarily resulted from the inclusion of many older subjects
(65 to 75 years±men >75 years) with no additional clinical stroke
risk factors.
ConclusionsThe age threshold for assigning an increased stroke risk has a dramatic impact on whether to recommend warfarin in populations of patients with NVAF. Large, prospective studies with many stroke events are needed to precisely determine the relationship of age to stroke risk in AF and to identify which AF subgroups are at a sufficiently low stroke risk to forego anticoagulation.
Key Words: fibrillation anticoagulants risk factors stroke
| Introduction |
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Stroke risk classification schemes have been proposed by the Atrial
Fibrillation Investigators (AFI), who performed a pooled
analysis of 5 primary prevention trials1 ; the
American College of Chest Physicians Consensus Conference on
Antithrombotic Therapy (ACCP), which used expert committees who
reviewed available published literature3 ; and the Stroke
Prevention in Atrial Fibrillation Investigators (SPAF), who
analyzed patients from a series of clinical
trials.4 These risk classification schemes were based
primarily on post hoc analyses of randomized trial populations.
Resulting treatment recommendations overlap but have several
differences (Table
). The implications of
these differences for the use of warfarin therapy in "real world"
populations of NVAF patients are unknown.
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To address this issue, we evaluated the impact of these 3 stroke risk classification schemes on the anticoagulation decision in a large cohort of ambulatory patients with NVAF.
| Methods |
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1 ECG demonstrating AF, with essentially all
such ECGs performed before the start of the ECG database in 1994. To identify adult NVAF patients with adequate data, we excluded patients without prior health plan membership, an age <18 years, transient AF due to recent cardiac surgery, known valvular heart disease, concomitant hyperthyroidism, or lack of internal medicine or cardiology care after the AF diagnosis.
We defined transient perioperative AF as a single outpatient AF diagnosis occurring up to 30 days after coronary bypass, pericardial, or cardiac repair surgery. Valvular disease was defined as an inpatient or outpatient diagnosis of mitral stenosis or prosthetic valve or previous mitral and/or aortic valve repair or replacement. Hyperthyroidism was defined as an inpatient or outpatient diagnosis of hyperthyroidism or thyrotoxicosis, an antithyroid medication prescription, or a low serum thyroid-stimulating hormone level (<0.03 µg/mL) during the 12 months before the first noted AF diagnosis. Corresponding diagnoses used for exclusion purposes were ascertained from comprehensive hospital discharge, billing claims, and outpatient databases for health plan admissions, out-of-network emergent care, and visits to emergency departments and outpatient clinics, respectively. The codes used have been previously described.5
Patient Characteristics
Proposed risk factors from 3 prominent stroke risk
classification schemes were identified1 3 4
(Table
). We approximated 2 of the SPAF criteria by using a
hypertension diagnosis for a "systolic blood pressure
>160 mm Hg" and a heart failure diagnosis for "recent heart
failure or fractional shortening <25% on
echocardiography."4 We examined the
outpatient database between June 1, 1994 and December 31, 1997 for
diagnoses of previous stroke, hypertension, heart failure, and
diabetes. The utility of this database for these diagnoses ranged from
good to outstanding.5 For previous stroke and heart
failure, we supplemented outpatient data with hospital discharge
diagnoses within 5 years before the AF diagnosis.
Comparison of Stroke Risk Criteria
Using the
statistic,6 we compared, across the
stroke risk criteria, the proportion of patients classified as having a
low enough risk for stroke that aspirin was an acceptable therapy; this
was defined as having none of the risk factors proposed by the
AFI,1 ACCP,3 or SPAF4
criteria.
| Results |
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65 years, and 45% was
75 years. Overall, 9% of patients had a previous ischemic stroke, 31% had previously diagnosed heart failure, 51% had hypertension, 17% had diabetes, and 29% had known coronary disease. Compared with patients in the first 5 primary prevention trials for AF,1 our cohort was older, had a higher proportion of women, and had a higher prevalence of stroke-related comorbidities.
Comparison of Stroke Risk Criteria
We compared the proportion of NVAF patients who would be
categorized as having a "low stroke risk," in which aspirin would
be a reasonable alternative to warfarin, across the 3 stroke risk
criteria (Figure
). The AFI criteria
classified 10.5% (n=1426) as having a low stroke risk, compared with
23.3% (n=3155) for the ACCP criteria and 29.3% (n=3973) for the SPAF
criteria (Figure
). Inclusion of patients with hyperthyroidism
did not change the results significantly. There was fair agreement
between AFI and ACCP (
=0.56) and AFI and SPAF (
=0.44) and
excellent agreement between ACCP and SPAF (
=0.85). More than 90% of
the difference in the proportion of patients considered to have a low
stroke risk by the ACCP and SPAF criteria compared with AFI was
explained by the inclusion of older patients (65 to 75 years and men
>75 years) with no other stroke risk factors.
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| Discussion |
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Previous studies have reported varying estimates of the proportion of patients who should be considered for warfarin therapy,8 9 10 but they were hampered by relatively small sample sizes8 9 or by using randomized trial populations, which are not representative of NVAF patients in actual clinical care.10 The predictive ability of existing stroke risk criteria are based primarily on data from randomized trials that included relatively few stroke events.1 4 11 These classification schemes were variably effective in predicting stroke risk in one relatively small population-based AF cohort.9 We showed that the choice of stroke risk criteria can have substantial impact on treatment recommendations within a large, ambulatory population of NVAF patients in usual clinical care.
Our study had limitations. We approximated 2 of the SPAF criteria (systolic blood pressure>160 mm Hg and left ventricular dysfunction) using diagnoses of hypertension and heart failure, respectively. However, this likely served to categorize fewer patients at low risk than if explicit SPAF criteria were used, which suggests even greater differences exist between the various schemes. We lacked echocardiographic data, which can provide additional relevant clinical information,12 but its marginal benefit above clinical risk factors for determining stroke risk remains unclear.8 It is possible that the exclusion of patients without health plan membership or outpatient follow-up care may affect the generalizability of our results. Finally, we could not distinguish between paroxysmal and persistent/permanent AF, but previous studies suggest that the risk of stroke is similar in these subgroups.13
In conclusion, prominent risk stratification schemes for NVAF patients
differ substantially in the proportion of patients considered to have a
low enough risk of stroke to recommend aspirin instead of warfarin.
These differences depend primarily on whether the age 65 to 75 years,
by itself, is viewed as a sizable risk factor for stroke in NVAF. These
differences have important implications for the
2 200 000
Americans with NVAF. Depending on the risk criteria, the number of US
NVAF patients considered at low risk would range from
225 000 to
nearly 650 000. Further compounding this problem is the more marked
variation in locally produced treatment guidelines for
AF.7 Therefore, large, prospective studies with many
stroke events are needed to precisely specify the risk of stroke
associated with increasing age and its interaction with other stroke
risk factors in the setting of NVAF.
| Acknowledgments |
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| Footnotes |
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Received April 4, 2000; revision received May 15, 2000; accepted May 15, 2000.
| References |
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