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Gregory Y. H. Lip, MD; Robby Nieuwlaat, PhD; Ron Pisters, MD; Deirdre A. Lane, PhD; Harry J. G. M. Crijns, MD
Author and Funding Information

From the University of Birmingham Centre for Cardiovascular Sciences (Drs Lip and Lane), City Hospital; and the Department of Cardiology (Drs Nieuwlaat, Pisters, and Crijns), Maastricht University Medical Centre.

Correspondence to: Gregory Y. H. Lip, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, England; e-mail: g.y.h.lip@bham.ac.uk


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Lip has served as a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, Aryx, and Boehringher and has been on the speakers bureau for Bayer, Boehringher, and Sanofi. Dr Pisters has served on the Roche advisory board. Dr Lane has received assistance to travel to the European Society of Cardiology from AstraZeneca. Drs Nieuwlaat and Crijns have reported no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(4):1020-1021. doi:10.1378/chest.10-0938
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To the Editor:

Singer et al feel that the CHA2DS2-VASc (Cardiac failure or dysfunction, Hypertension, Age ≥ 75[Doubled], Diabetes, Stroke[Doubled] - Vascular disease, Age 65-74 and Sex category [Female]) (Birmingham 2009) schema is too premature for clinical application, but our schema is essentially an adaptation/refinement of the widely applied 2006 American College of Cardiology (ACC)/American Heart Association (AHA)/European Society of Cardiology (ESC) guidelines risk schema1 that takes into account recent research evidence.

Recent schema largely incorporates the same risk factors, and small differences in C statistics are shown by us2 and Fang et al.3 Differences might only be statistically different when using a very large cohort, especially when correcting for multiple comparisons. Our aim was to fine-tune risk stratification by adding evidence from our cohort (and other recent research) to current known-risk factors in a practically useful schema. The desirable large C statistic improvements might only be expected when making a schema substantially more complex or adding multiple biomarkers/genes. Although the Framingham score performed better than chance when (artificially) categorized into three risk strata, this schema requires a risk calculator, categorizes many as low (48.3%) or intermediate (41.5%) risk, and is impractical for everyday use.

We have “validated” the schema in the sense that we used a combination of the existing CHADS2 score added to gender, age 65 to 74 years, and vascular disease (all already listed in the 2006 ACC/AHA/ESC guidelines as “less validated” moderate risk factors). In keeping with new data, the CHA2DS2-VASc score recognizes the importance of age ≥ 75 years as a major risk factor.

We stated that ongoing validations of the CHA2DS2-VASc score in other populations will confirm its true value, and one presented analysis in ~80,000 atrial fibrillation (AF) patients confirms the usefulness of CHA2DS2-VASc.4 We initially used the stepwise approach to test which factors were significantly associated with thromboembolism in the Euro Heart Survey “derivation cohort,” which were gender and vascular disease. However, in the final analysis of the CHA2DS2-VASc score, we kept all risk factors in the model and reported their performance in Table 4 (no stepwise method was applied).

We apologize for the typo in the 95% CI of (0-0) in Table 6; the correct 95% CI should read (0.0-3.5), which reflects the modest statistical power of our analysis. For everyday clinical use, it is still preferable to have a small intermediate-risk group (avoiding the “aspirin or warfarin” uncertainty) and to be better at filtering out the “truly low-risk” patients who will receive less benefit from antithrombotic therapy (with potential harm from bleeding).

We have already acknowledged that a major limitation was the absence of information on thromboembolism for 31% of the patients, but a strength of our analysis was its prospective nature, which allowed better standardization of definitions and identification of events, compared with retrospective record linkage data. Patients lost to follow-up were more diseased and, if anything, we have probably underestimated the overall thromboembolic event rate.

Overall, a valuable risk stratification tool should have good predictive ability, be practically useful, and take into account acceptable absolute event rates and the net risk-benefit for linking risk scores to treatment recommendations. Regarding the last, most patients in randomized trials that show the efficacy of oral anticoagulation have only one or two stroke risk factors, and in clinical practice, more of such patients are being considered for anticoagulant therapy. We feel the CHA2DS2-VASc score improves identification of “truly low-risk” patients, without increasing the “intermediate-risk” category (with the uncertainty of “warfarin or aspirin”), and will assist in delivering oral anticoagulation (especially with new agents on the horizon) to more patients with AF who are likely to benefit.

Fuster V, Rydén LE, Cannom DS, et al; Task Force on Practice Guidelines, American College of Cardiology/American Heart Association Task Force on Practice Guidelines, American College of Cardiology/American Heart Association Committee for Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Society of Cardiology European Heart Rhythm Association European Heart Rhythm Association Heart Rhythm Society Heart Rhythm Society ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Eur Heart J. 2006;2716:1979-2030. [CrossRef] [PubMed]
 
Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest. 2010;1372:263-272. [CrossRef] [PubMed]
 
Fang MC, Go AS, Chang Y, Borowsky L, Pomernacki NK, Singer DE. ATRIA Study Group ATRIA Study Group Comparison of risk stratification schemes to predict thromboembolism in people with nonvalvular atrial fibrillation. J Am Coll Cardiol. 2008;518:810-815. [CrossRef] [PubMed]
 
van Staa TP, Zhang B, Setakis E, Lane D, Lip GY. Comparison of risk stratification schemes for stroke in atrial fibrillation. Circulation. 2009;120:S521
 

Figures

Tables

References

Fuster V, Rydén LE, Cannom DS, et al; Task Force on Practice Guidelines, American College of Cardiology/American Heart Association Task Force on Practice Guidelines, American College of Cardiology/American Heart Association Committee for Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Society of Cardiology European Heart Rhythm Association European Heart Rhythm Association Heart Rhythm Society Heart Rhythm Society ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Eur Heart J. 2006;2716:1979-2030. [CrossRef] [PubMed]
 
Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest. 2010;1372:263-272. [CrossRef] [PubMed]
 
Fang MC, Go AS, Chang Y, Borowsky L, Pomernacki NK, Singer DE. ATRIA Study Group ATRIA Study Group Comparison of risk stratification schemes to predict thromboembolism in people with nonvalvular atrial fibrillation. J Am Coll Cardiol. 2008;518:810-815. [CrossRef] [PubMed]
 
van Staa TP, Zhang B, Setakis E, Lane D, Lip GY. Comparison of risk stratification schemes for stroke in atrial fibrillation. Circulation. 2009;120:S521
 
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