Higher CHADS2 score associated with elevated risk for stroke, death in atrial fibrillation 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 ₂CHADS 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 atrial fibrillation.

"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."

We know that the higher the CHADS2 score, the greater the risk for stroke, whether or not the patient is on an anticoagulant. Patients on dabigatran who had a higher CHADS2 score were at higher risk for stroke than patients with lower scores, but the reduction in stroke was significant compared with warfarin at all CHADS2 scores. People who have higher degrees of stroke risk also are at higher risk for major bleeding or bleeding of any kind. The data demonstrate that, except for GI bleeds, bleeding in patients randomized to dabigatran was lower than in patients randomized to warfarin. While the number of GI bleeds was slightly higher in the dabigatran group, the number of intracranial bleeds was far, far lower. Another way of interpreting this data is as follows: Dabigatran changes the types of bleeds patients might experience from head bleeds to GI bleeds. Head bleeds can be catastrophically debilitating and even life-threatening. GI bleeds might be serious, but they are usually not as life-threatening or as likely to result in irreversible organ dysfunction.

Zayd A. Eldadah, MD, PhD
Director of Cardiac Arrhythmia Research
Washington Hospital Center, Washington, D.C.

Disclosure: Dr. Eldadah reports no relevant financial disclosures.

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