November 22, 2011 — In patients with atrial fibrillation, higher CHADS2 score is associated with increased risk for stroke or systemic embolism, bleeding, and death, even with optimal anticoagulation with warfarin or dabigatran, according to a subgroup analysis of the RE-LY trial.
In anticoagulated patients, "the commonly used CHADS2 risk score not only predicts stroke (as it was developed for) but also mortality and major bleeding," first author Jonas Oldgren, MD, associate professor of cardiology, Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala University Hospital, Sweden, told Medscape Medical News.
The analysis was published November 15 in Annals of Internal Medicine.
Prediction Rule
CHADS2 is a simple and validated clinical prediction rule for estimating stroke risk in patients with atrial fibrillation not receiving anticoagulants, the authors note in their paper. Its value in predicting thrombotic and bleeding complications in patients receiving anticoagulant therapy is unclear.
Dr. Oldgren and colleagues used data from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial to assess thrombotic and bleeding risk according to the baseline CHADS2 score.
The study involved 18,112 patients with atrial fibrillation at risk for stroke who were randomly assigned to treatment with dabigatran (Pradaxa, Boehringer Ingelheim), 110 mg or 150 mg twice daily, or warfarin at a dose adjusted to an international normalized ratio (INR) of 2.0 to 3.0 for a median of 2 years.
The main RE-LY results, published in 2009 in the New England Journal of Medicine, showed that the rates of stroke or systemic embolism and death each decreased by 0.5% per year with dabigatran, 150 mg twice daily, compared with dose-adjusted warfarin. Rates of major bleeding did not differ, but intracranial bleeding was less common with dabigatran.
The CHADS2 risk score assigns 1 point for a history of congestive heart failure, hypertension, diabetes, or age older than 75 years and 2 points for a history of stroke or transient ischemic attack.
In the RE-LY cohort, 5775 patients had CHADS2 scores of 0 to 1, 6455 had scores of 2, and 5882 patients had scores of 3 to 6.
Even with anticoagulation, the risk for the primary outcome of stroke or systemic embolism increased with increasing CHADS2 score, the authors report.
Table 1. Annual Rates of Primary Outcome by CHADS2 Score
There was also a progressive near-linear increase in the risk for other outcomes with increasing CHADS2 score, the authors report.
Table 2. Annual Rates of Other Outcomes by CHADS2 Score
P < .001 for all comparisons.
Regardless of CHADS2 score, "rates of stroke or systemic embolism were lower with dabigatran, 150 mg twice daily, and rates of intracranial bleeding were lower with both dabigatran doses than with warfarin treatment," Dr. Oldgren told Medscape Medical News.
These findings "extend our knowledge in important ways," write the authors of a linked commentary.
"CHADS2 scores of 3 or higher identify patients with the most to gain and the most to lose by using anticoagulant therapy," note Rebecca J. Beyth, MD, University of Florida, Gainesville, and C. Seth Landefeld, MD, University of California, San Francisco.
"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," they add.
Interpret Cautiously
Dr. Oldgren and colleagues caution that these subgroup analyses were not prespecified and "should be deemed exploratory."
Nonetheless, "we believe these results are valuable for clinicians in their daily practice and useful in the decision on oral anticoagulant treatment in patients with atrial fibrillation at risk for stroke," Dr. Oldgren told Medscape Medical News.
Dr. Beyth and Dr. Landefeld agree. They say these data along with other studies performed to date can help physicians choose whether to use dabigatran or warfarin.
"On the one hand, dabigatran is more effective and safer for many patients with nonvalvular atrial fibrillation, especially younger patients, patients with CHADS2 scores of 0 or 1, and those in whom the INR is not maintained within the therapeutic range at least 60% of the time," they point out.
"On the other hand, the relative benefits of warfarin and dabigatran depend on the proportion of time that the INR is maintained within the therapeutic range in patients receiving warfarin and on patients adhering to a twice-daily regimen of dabigatran," they note.
The study was funded by Boehringer Ingelheim Pharmaceuticals. A complete list of disclosures for the RE-LY investigators and editorial writers can be found on the journal's Web site.
Ann Intern Med. 2011;155:660-667, 714-715. Study abstract Editorial extract
In anticoagulated patients, "the commonly used CHADS2 risk score not only predicts stroke (as it was developed for) but also mortality and major bleeding," first author Jonas Oldgren, MD, associate professor of cardiology, Uppsala Clinical Research Centre and Department of Medical Sciences, Uppsala University Hospital, Sweden, told Medscape Medical News.
The analysis was published November 15 in Annals of Internal Medicine.
Prediction Rule
CHADS2 is a simple and validated clinical prediction rule for estimating stroke risk in patients with atrial fibrillation not receiving anticoagulants, the authors note in their paper. Its value in predicting thrombotic and bleeding complications in patients receiving anticoagulant therapy is unclear.
Dr. Oldgren and colleagues used data from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial to assess thrombotic and bleeding risk according to the baseline CHADS2 score.
The study involved 18,112 patients with atrial fibrillation at risk for stroke who were randomly assigned to treatment with dabigatran (Pradaxa, Boehringer Ingelheim), 110 mg or 150 mg twice daily, or warfarin at a dose adjusted to an international normalized ratio (INR) of 2.0 to 3.0 for a median of 2 years.
The main RE-LY results, published in 2009 in the New England Journal of Medicine, showed that the rates of stroke or systemic embolism and death each decreased by 0.5% per year with dabigatran, 150 mg twice daily, compared with dose-adjusted warfarin. Rates of major bleeding did not differ, but intracranial bleeding was less common with dabigatran.
The CHADS2 risk score assigns 1 point for a history of congestive heart failure, hypertension, diabetes, or age older than 75 years and 2 points for a history of stroke or transient ischemic attack.
In the RE-LY cohort, 5775 patients had CHADS2 scores of 0 to 1, 6455 had scores of 2, and 5882 patients had scores of 3 to 6.
Even with anticoagulation, the risk for the primary outcome of stroke or systemic embolism increased with increasing CHADS2 score, the authors report.
Table 1. Annual Rates of Primary Outcome by CHADS2 Score
| CHADS2 Score | Stroke/Systemic Embolism (%) |
| 0 to 1 | 0.93 |
| 2 | 1.22 |
| 3 to 6 | 2.24 |
There was also a progressive near-linear increase in the risk for other outcomes with increasing CHADS2 score, the authors report.
Table 2. Annual Rates of Other Outcomes by CHADS2 Score
| CHADS2 Score | Major Bleeding (%) | Intracranial Bleeding (%) | Vascular Mortality (%) |
| 0 to 1 | 2.26 | 0.31 | 1.35 |
| 2 | 3.11 | 0.40 | 2.39 |
| 3 to 6 | 4.42 | 0.61 | 3.68 |
Regardless of CHADS2 score, "rates of stroke or systemic embolism were lower with dabigatran, 150 mg twice daily, and rates of intracranial bleeding were lower with both dabigatran doses than with warfarin treatment," Dr. Oldgren told Medscape Medical News.
These findings "extend our knowledge in important ways," write the authors of a linked commentary.
"CHADS2 scores of 3 or higher identify patients with the most to gain and the most to lose by using anticoagulant therapy," note Rebecca J. Beyth, MD, University of Florida, Gainesville, and C. Seth Landefeld, MD, University of California, San Francisco.
"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," they add.
Interpret Cautiously
Dr. Oldgren and colleagues caution that these subgroup analyses were not prespecified and "should be deemed exploratory."
Nonetheless, "we believe these results are valuable for clinicians in their daily practice and useful in the decision on oral anticoagulant treatment in patients with atrial fibrillation at risk for stroke," Dr. Oldgren told Medscape Medical News.
Dr. Beyth and Dr. Landefeld agree. They say these data along with other studies performed to date can help physicians choose whether to use dabigatran or warfarin.
"On the one hand, dabigatran is more effective and safer for many patients with nonvalvular atrial fibrillation, especially younger patients, patients with CHADS2 scores of 0 or 1, and those in whom the INR is not maintained within the therapeutic range at least 60% of the time," they point out.
"On the other hand, the relative benefits of warfarin and dabigatran depend on the proportion of time that the INR is maintained within the therapeutic range in patients receiving warfarin and on patients adhering to a twice-daily regimen of dabigatran," they note.
The study was funded by Boehringer Ingelheim Pharmaceuticals. A complete list of disclosures for the RE-LY investigators and editorial writers can be found on the journal's Web site.
Ann Intern Med. 2011;155:660-667, 714-715. Study abstract Editorial extract
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