Patients with elevated CHADS2 scores were at greater risk for stroke or
systemic embolism, bleeding and death when treated with oral anticoagulants for
atrial fibrillation, according to results of a subgroup analysis of the RE-LY
The CHADS2 score, a validated measure of risk, assigns patients 1 point
for a history of congestive heart failure, hypertension, age of 75 years or
older and diabetes mellitus, and 2 points for a history of stroke or transient
The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY)
trial compared outcomes for patients with atrial fibrillation at increased risk
for stroke assigned to twice daily 150 mg
dabigatran (Pradaxa, Boehringer Ingelheim) or twice daily 110
mg dabigatran vs. open-label
warfarin (Coumadin, Bristol-Meyers Squibb). Patients were
segregated into three groups, according to CHADS2 score: zero to 1
(n=5,775), 2 (n=6,455) or 3 to 6 (n=5,882). Nearly two-thirds of patients with
a score of zero to 1 (58.8%) had hypertension, the most individual component of
the CHADS2 score in that group. In patients with a score of 3 to 6,
more than 90% had hypertension, most had previously experienced a stroke or
transient ischemic attack, and/or were aged 75 years or older.
Overall, rate of stroke or systemic embolism increased for each 1-point
increase in risk score in all groups, ranging from 0.53% per year with a score
of zero, to 5.4% per year with a score of 6 (P=.001). CHADS2
scores were associated with increased event rates in all three study treatment
Researchers observed an increase in the annual rate of major bleeding
for each 1-point increase in the
CHADS2 score, from 1.6% per year in patients with
the lowest score, to 5.4% per year in patients with a score of 6. Major
bleeding also increased in relation to the CHADS2 score in both
Rates of vascular mortality were low in patients with the lowest scores
and rose with every 1-point increase in CHADS2 score, from 1.34% per
year for those with a score of 1, to 10.8% per year for patients with a score
of 6. Similarly, rates of total mortality went up, from 2.28% (95% CI,
2.00-2.58) per year with a score of 1, to 13.5% (CI, 8.24-20.8) per year with a
score of 6.
Writing in an accompanying editorial, Rebecca J. Beyth, MD, with
North Florida/South Georgia Veterans Health System and the University of
Florida, and C. Seth Landefeld, MD, with the University of California,
San Francisco, and the San Francisco VA Medical Center, said the findings
identify an important risk factor for patients with AF.
"Patients with higher CHADS2 scores are at increased risk for stroke,
even with optimal anticoagulation, and have a higher risk for major bleeding
and death," they wrote. "Thus, CHADS2 scores of 3 or higher identify patients
with the most to gain and the most to lose by using anticoagulant therapy.
Whether they receive warfarin or dabigatran, 150 mg twice daily, these patients
have a 2% to 3% annual risk for stroke or systemic embolism, a nearly 5% risk
for major bleeding, and a nearly 6% risk for death."
Disclosure: The researchers report no relevant financial disclosures.