Study Overview
Objective. To determine if CHA 2DS2-VASc score, a score commonly used to assess risk of cerebrovascular events among adults with atrial fibrillation, predicts ischemic stroke, thromboembolism, and death in a cohort of patients with heart failure with and without atrial fibrillation.
Design. Prospective cohort study.
Setting and participants . Patients in Denmark aged 50 years or older discharged with a primary diagnosis of incident heart failure between 1 Jan 2000 and 31 December 2012. Patients with atrial fibrillation were identified by a hospital diagnosis of atrial fibrillation or atrial flutter from 1994 onwards. The study excluded patients treated with vitamin K antagonist within 6 months prior to heart failure diagnosis and patients with a diagnosis of cancer or chronic obstructive pulmonary disease. The study utilized 3 national Danish registries: the National Patient Registry (which records all hospital admissions and diagnoses using ICD-10), the National Prescription Registry (prescription data), and the Civil Registry System (demographics and vital statistics). The registries were linked and have been well validated.
Main outcome measure . The primary outcome measure was defined as a hospital diagnosis of ischemic stroke or thromboembolic events, transient ischemic attack, systemic embolism, pulmonary embolism or myocardial infarction within 1 year after heart failure diagnosis. A secondary outcome measure was all-cause death at 1 year.
Analysis. Patients were risk stratified using the CHA 2DS2-VASc score. Patients were given 1 point for congestive heart failure, hypertension, age 65 to 74 years, diabetes mellitus, vascular disease, and female sex and 2 points for age 75 years or older and previous thromboembolic events. The authors conducted a time-to-event analysis to examine the relationship between CHA 2DS2-VASc score and the risk of ischemic stroke, thromboembolic event, and death separately among those with atrial fibrillation and without. Patients were censored if they began anticoagulation therapy during follow-up. The properties of CHA 2DS2-VASc score in predicting the risk of outcomes were quantified using C statistics. Multiple sensitivity analyses were conducted to account for patients who had a diagnosis of atrial fibrillation shortly after diagnosis of heart failure, to include patients with chronic obstructive pulmonary disease, and split sample analysis by date of heart failure diagnosis was conducted.
Main results . A total of 42,987 patients with incident heart failure during 2000–2012 were included in the cohort, with 21.9% of these having atrial fibrillation at baseline. The median follow-up period was 1.8 years. For patients with heart failure with or without a diagnosis of atrial fibrillation, the 1-year absolute risk for all outcomes were high and increased with increasing CHA 2DS2-VASc score. For ischemic stroke and death, absolute risks were higher among patient with heart failure and atrial fibrillation when compared with patients without atrial fibrillation. At high CHA 2DS2-VASc score, the risk of thromboembolism was higher among patients without atrial fibrillation when compared with those with atrial fibrillation. CHA 2DS2-VASc score predicted the end point of ischemic stroke at 1 and 5 years modestly with C statistics 0.67 and 0.69 among those without atrial fibrillation and 0.64 and 0.71 among those with atrial fibrillation. The negative predictive value for all events at 1 year was around 90% when using a cutoff score of 1 for patients without atrial fibrillation, but only around 75% at 5 years.
Conclusions. Although the CHA 2DS2-VASc score was developed to predict ischemic stroke among patients with atrial fibrillation, it also has modest predictive accuracy when applied to patients with heart failure without atrial fibrillation. Among patients with heart failure with a high CHA 2DS2-VASc score, the risks of all adverse outcomes were high regardless of whether concomitant atrial fibrillation was present, and the risk of thromboembolism was higher among those without atrial fibrillation than those with concomitant atrial fibrillation. Because of the modest predictive accuracy, the clinical utility of CHA 2DS2-VASc among patients with heart failure needs to be further determined.
Commentary
Clinical prediction rules are increasingly relied upon in clinical setting to drive medical decision making, allowing clinicians to weigh risks and benefits of interventions in a concrete, evidence-based manner [1]. The CHA 2DS2-VASc score, endorsed in guidelines for assessing risk of stroke among patients with atrial fibrillation, is widely used in clinical practice [2,3] in helping make decisions about treatment, such as use of anticoagulation. The use of the clinical prediction rule for patients with heart failure but without atrial fibrillation is a novel application of the widely used rule. The rationale is that the CHA 2DS2-VASc score includes within it a cluster of stroke risk factors that increases risk of stroke whether atrial fibrillation is present or not and thus perhaps capture stroke risk beyond whether a patient has atrial fibrillation [4]. The authors selected a patient group with high rate of mortality—those with incident heart failure—to evaluate the hypothesis that the CHA 2DS2-VASc score could predict stroke outcomes in heart failure patients without atrial fibrillation in a manner similar to that in atrial fibrillation populations, and that at high CHA 2DS2-VASc scores, the risk for stroke would be comparable among heart failure patients.
What the authors found is that the scoring algorithm was able to predict stroke occurrence modestly whether or not atrial fibrillation was present, and that stroke risk was high among those at the highest scores regardless of whether patients had atrial fibrillation. These findings underscore the potential use of the scoring algorithm beyond the population with atrial fibrillation, and also highlighted the need for further research in the highest risk group of heart failure patients without atrial fibrillation to determine whether anticoagulation may reduce stroke risk in this population. Minor study limitations included the use of an administrative dataset, in which diagnosis information may be incomplete or erroneous, and the potential limited generalizability of the study, given differences in the makeup of the Danish study population compared with other populations.
Applications for Clinical Practice
The study explores the use of clinical predication rule beyond the condition for which it is developed and found that particularly in high-risk groups, risk scores still predicted adverse events, albeit modestly. For clinicians, it highlights both the utility of the risk scores and the current gap in knowledge about stroke prevention in the highest-risk group of patients without atrial fibrillation. Further studies are needed to determine if anticoagulation therapy applies to this high-risk group for stroke prevention.
—William W. Hung, MD, MPH