Comparison of risk stratification schemes to predict thromboembolism in people with nonvalvular atrial fibrillation

Margaret C Fang, Alan S Go, Yuchiao Chang, Leila Borowsky, Niela K Pomernacki, Daniel E Singer, ATRIA Study Group, Margaret C Fang, Alan S Go, Yuchiao Chang, Leila Borowsky, Niela K Pomernacki, Daniel E Singer, ATRIA Study Group

Abstract

Objectives: We assessed 5 risk stratification schemes for their ability to predict atrial fibrillation (AF)-related thromboembolism in a large community-based cohort.

Background: Risk schemes can help target anticoagulant therapy for patients at highest risk for AF-related thromboembolism. We tested the predictive ability of 5 risk schemes: the Atrial Fibrillation Investigators, Stroke Prevention in Atrial Fibrillation, CHADS(2) (Congestive heart failure, Hypertension, Age >or= 75 years, Diabetes mellitus, and prior Stroke or transient ischemic attack) index, Framingham score, and the 7th American College of Chest Physicians Guidelines.

Methods: We followed a cohort of 13,559 adults with AF for a median of 6.0 years. Among non-warfarin users, we identified incident thromboembolism (ischemic stroke or peripheral embolism) and risk factors from clinical databases. Each scheme was divided into low, intermediate, and high predicted risk categories and applied to the cohort. Annualized thromboembolism rates and c-statistics (to assess discrimination) were calculated for each risk scheme.

Results: We identified 685 validated thromboembolic events that occurred during 32,721 person-years off warfarin therapy. The risk schemes had only fair discriminating ability, with c-statistics ranging from 0.56 to 0.62. The proportion of patients assigned to individual risk categories varied widely across the schemes. The proportion categorized as low risk ranged from 11.7% to 37.1% across schemes, and the proportion considered high risk ranged from 16.4% to 80.4%.

Conclusions: Current risk schemes have comparable, but only limited, overall ability to predict thromboembolism in persons with AF. Recommendations for antithrombotic therapy may vary widely depending on which scheme is applied for individual patients. Better risk stratification is crucially needed to improve selection of AF patients for anticoagulant therapy.

Figures

Figure 1. Annual TE Rates Across Risk…
Figure 1. Annual TE Rates Across Risk Groups Using 5 Risk Stratification Schemes Used to Predict AF-Related TE
The double-barred lines represent 95% confidence intervals. ACCP = American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy; AF = atrial fibrillation; AFI = Atrial Fibrillation Investigators; CHADS2 = congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; SPAF = stroke prevention in atrial fibrillation; TE = thromboembolism.
Figure 2. Proportion of ATRIA Cohort Off…
Figure 2. Proportion of ATRIA Cohort Off Warfarin and Categorized by CHADS2 Scores, Stratified by Development of TE
The distribution of person-years contributed by patients not sustaining a TE is in blue and the distribution of person-years contributed by patients sustaining a TE is in yellow. Abbreviations as in Figure 1.
Figure 3. ROC Curves for 5 Risk…
Figure 3. ROC Curves for 5 Risk Stratification Schemes Used to Predict AF-Related Thromboembolism
The 45° dotted line represents the line of no information. ROC = receiver-operating characteristic; other abbreviations as in Figure 1.

References

    1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study. Arch Intern Med. 1987;147:1561–1564.
    1. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from 5 randomized controlled trials. Arch Intern Med. 1994;154:1449–1457.
    1. Gage BF, van Walraven C, Pearce L, et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation. 2004;110:2287–2292.
    1. Pearce L, Hart R, Halperin J. Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation. Am J Med. 2000;109:45–51.
    1. Go AS, Hylek EM, Phillips KA, et al. Implications of stroke risk criteria on the anticoagulation decision in nonvalvular atrial fibrillation: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. Circulation. 2000;102:11–13.
    1. Hart R, Pearce L, McBride R, Rothbart R, Asinger R. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. Stroke. 1999;30:1223–1229.
    1. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285:2864–2870.
    1. Wang TJ, Massaro JM, Levy D, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA. 2003;290:1049–1056.
    1. Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:429S–456S.
    1. Go AS, Hylek EM, Borowsky LH, Phillips KA, Selby JV, Singer DE. Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. Ann Intern Med. 1999;131:927–934.
    1. Go AS, Hylek EM, Chang Y, et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? JAMA. 2003;290:2685–2692.
    1. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.
    1. Hosmer D, Lemeshow S. Applied Logistic Regression. 2nd Edition. New York, NY: Wiley; 2000.
    1. Fang MC, Singer DE, Chang Y, et al. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) study. Circulation. 2005;112:1687–1691.
    1. Conway DS, Pearce LA, Chin BS, Hart RG, Lip GY. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation. 2003;107:3141–3145.
    1. Lip GY, Lane D, Van Walraven C, Hart RG. Additive role of plasma von Willebrand factor levels to clinical factors for risk stratification of patients with atrial fibrillation. Stroke. 2006;37:2294–2300.
    1. Go AS, Reed GL, Hylek EM, et al. Factor V Leiden and risk of ischemic stroke in nonvalvular atrial fibrillation: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. J Thromb Thrombolysis. 2003;15:41–46.
    1. Chambless LE, Folsom AR, Sharrett AR, et al. Coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC) study. J Clin Epidemiol. 2003;56:880–890.
    1. Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006;355:2631–2639.
    1. Blankenberg S, McQueen MJ, Smieja M, et al. Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) study. Circulation. 2006;114:201–208.
    1. Folsom AR, Chambless LE, Ballantyne CM, et al. An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study. Arch Intern Med. 2006;166:1368–1373.
    1. Cook NR. Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation. 2007;115:928–935.
    1. Levine MN, Raskob G, Beyth RJ, Kearon C, Schulman S. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(Suppl 3):287S–310S.
    1. Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL. National surveillance of emergency department visits for outpatient adverse drug events. JAMA. 2006;296:1858–1866.
    1. Fang MC, Chang Y, Hylek EM, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med. 2004;141:745–752.
    1. Fang MC, Go AS, Chang Y, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med. 2007;120:700–705.
    1. Arima H, Hart RG, Colman S, et al. Perindopril-based blood pressure-lowering reduces major vascular events in patients with atrial fibrillation and prior stroke or transient ischemic attack. Stroke. 2005;36:2164–2169.
    1. Albers GW, Diener HC, Frison L, et al. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA. 2005;293:690–698.
    1. Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367:1903–1912.

Source: PubMed

3
購読する