JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 65, NO. 3, 2015

ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER INC.

http://dx.doi.org/10.1016/j.jacc.2014.11.013

EDITORIAL COMMENT

Adding Rigor to Stroke Risk Prediction in Atrial Fibrillation* Daniel E. Singer, MD,y Michael D. Ezekowitz, MBCHB, DPHILz

G

uidelines recommend oral anticoagulant

cohort-to-cohort variation in reported CHA2DS 2-VASc–

(OAC) therapy for patients with atrial fibril-

stratified rates of stroke for nonanticoagulated AF

lation (AF) on the basis of ischemic stroke

patients. Second, they reveal how sensitive estimates

risk. Guidelines from both the United States (Amer-

of stroke rates are to variations in interrogating

ican College of Cardiology/American Heart Associa-

administrative databases, which are used repeatedly

tion/Heart Rhythm Society [AHA/ACC/HRS]) (1) and

as sources of “real-world” rates of stroke. Friberg

from Europe (European Society of Cardiology [ESC])

et al. underscore the inappropriate use of TIA as

(2) use the CHA2DS2-VASc risk score (3) and recom-

an outcome, false-positive events when stroke codes

mend a low threshold for OAC use. The ESC guideline

are secondary diagnoses, and the importance of

proposes anticoagulation therapy for patients with $1

excluding stroke events recorded shortly after the

risk factor ($1 point), whereas the AHA/ACC/HRS

first AF diagnosis. They conclude that the true stroke

guideline uses a threshold of 2 points. Because ESC

rate for patients with a CHA 2DS2 -VASc score of 1

does not consider female sex as a stand-alone risk fac-

is #0.7% per year, too low for OAC therapy to benefit

tor, the difference between the recommendations di-

patients with AF.

minishes. In effect, the ESC guideline recommends

Since clinical risk factors for stroke with AF were

anticoagulation therapy for w90% of patients with

first identified (6), guidelines have adopted a risk-

AF and the AHA/ACC/HRS guideline for w85% (4).

based perspective. The underlying principle is that

SEE PAGE 225

the benefit from the expected absolute reduction in ischemic stroke risk from OAC therapy must exceed

In this issue of the Journal, Friberg et al. (5) make

the expected harm from increased bleeding. The

2 important observations regarding risk score thresh-

relative risk reduction estimated from randomized

olds for OAC therapy. First, they highlight the wide

trials of OAC therapy versus no OAC therapy is assumed to be constant across risk groups. The absolute risk reduction then varies according to patients’

*Editorials published in the Journal of the American College of Cardiology

untreated risk of stroke: higher-risk patients should

reflect the views of the authors and do not necessarily represent the

receive anticoagulation therapy, whereas lower-risk

views of JACC or the American College of Cardiology.

patients might avoid it. Unfortunately, randomized

From the yDivision of General Internal Medicine, Massachusetts General

trials provide little information directly bearing on

Hospital and Harvard Medical School, Boston, Massachusetts; and the

how OAC agents affect the lowest-risk patients.

zSidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania. Dr. Singer has served as a consultant or on the

The CHADS 2 score provided a simple summary of

advisory boards of Boehringer Ingelheim, Bristol-Myers Squibb, Johnson

AF stroke risk factors using an easily remembered

& Johnson, Merck & Co., Inc., and St. Jude Medical; and has received

acronym (1 point each for congestive heart failure,

research funding from Boehringer Ingelheim, Bristol-Myers Squibb,

hypertension, age $75 years, and diabetes, plus 2

Johnson & Johnson, and Medtronic. Dr. Singer was supported, in part, by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General

points for prior stroke/TIA) (7) and was widely

Hospital. This funding source had no role in the preparation of the

adopted. Guidelines recommended anticoagulation

manuscript. Dr. Ezekowitz has served as a consultant or on the advisory boards of Boehringer Ingelheim, Pfizer, Sanofi, Bristol-Myers Squibb, Portola, Bayer, Daiichi Sankyo, Medtronic, Janssen Scientific Affairs,

for AF patients with $1 CHADS2 points implicitly using a 2% per year (untreated) stroke risk threshold

Aegerion, Merck & Co., Inc., Johnson & Johnson, Gilead, Pozen, Amgen,

based on the original CHADS 2 cohort. The CHADS2

Coherex, and Armetheon.

score is notably limited by using a single age cutoff,

234

Singer and Ezekowitz

JACC VOL. 65, NO. 3, 2015 JANUARY 27, 2015:233–5

Stroke Risk in Atrial Fibrillation

when age is known to be a strong continuous risk

undergo OAC therapy, but patients with only 1 of

factor (8). In 2010, Lip et al. (3) proposed the

the other factors may be below the 1% per year

CHA2DS 2-VASc score, adding to the CHADS 2 score age

threshold.

65 to 74 years, female sex, and vascular disease

Adding uncertainty is the fact that the point score

(hence “VASc”) counting 1 point each, while age $75

threshold exceeding an untreated annual stroke risk

years was assigned 2 points. Patients between 65 and

of 1% or 2% varies according to the cohort studied. In

74 years of age undoubtedly possess higher risk than

general, biases in measuring AF stroke rates tend to

younger patients, and female sex has generally been

result in overestimates (5). Furthermore, the dramatic

validated as a risk factor for stroke in AF. In contrast,

secular decrease in overall stroke rates seen in recent

multiple large studies have found that vascular dis-

years may apply to AF as well (12). These consider-

ease is either not an independent risk factor for

ations urge caution in setting very low point score

stroke in AF or produces a very small independent

thresholds for anticoagulation therapy.

effect (