Higher CHADS2 score associated with elevated risk for stroke, death in AF after oral anticoagulant treatment

Oldgren J. Ann Intern Med. 2011;155:660-667.

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 trial.

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 ischemic attack.

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 groups.

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 treatment groups.

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.

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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 trial.

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 ischemic attack.

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 groups.

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 treatment groups.

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.

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