COPENHAGEN, DENMARK. Atrial fibrillation (AF) with underlying heart disease or other comorbidities is associated with an increased risk of ischemic stroke. Thus, treatment with aspirin or vitamin K antagonists (warfarin) is often recommended for AF patients. The justification for prescribing aspirin or warfarin is based on the results of closely controlled clinical trials, which may or may not reflect the "real world". A study reported in 2003 found that warfarin therapy had no net benefit in AF patients with no risk factors for ischemic stroke, but was of significant benefit to those who had previously suffered an ischemic stroke.
A team of Danish and British researchers now reported on a major study aimed at determining the benefits of aspirin and warfarin therapy in a "real world" setting. The study included 132,372 AF patients discharged from hospital with a diagnosis of non-valvular AF (AF without a previous diagnosis of mitral or aortic valve disease, and absence of mitral or aortic valve surgery). As Danish citizens, all study participants had a unique person registration number which allowed precise linking of databases regarding hospital admissions, drug prescriptions, vital statistics, comorbid conditions, and causes of death. Of the 132,372 AF patients discharged between 1997 and 2008, 44.5% (58,883 patients) were not prescribed aspirin or anticoagulants (no treatment), 28.3% (37,425 patients) were prescribed an anticoagulant (vitamin K antagonist – most likely warfarin), 18.9% (24,984 patients) were prescribed aspirin, and the remaining 8.4% (11,080 patients) were prescribed both aspirin and anticoagulant at discharge.
Access to the comprehensive databases made it possible to construct risk scores for ischemic stroke and bleeding for each of the 132,372 patients. The following risk scores were used:
- CHADS2 – This scoring system assigns 1 point each to the presence of congestive heart failure, hypertension, diabetes, age of 75 years or older, and 2 points for a history of stroke or transient ischemic attack (TIA).
- CHA2DS2-VASc – This score assigns 1 point each to the presence of congestive heart failure, hypertension, diabetes, vascular disease, age 65 to 74 years, female gender, and 2 points for a history of thromboembolism and age 75 years or older.
- HAS-BLED – This scoring system assigns 1 point each for the presence of hypertension, abnormal liver/kidney function, history of thromboembolism, history of bleeding, alcohol or drug abuse, and age above 65 years. One point is also assigned to warfarin-treated patients whose INR values fluctuate excessively (not used in this study).
Primary study outcomes were hospitalizations or deaths from thromboembolism (ischemic stroke, TIA and peripheral artery embolism) or bleeding (gastrointestinal bleeding, intracranial bleeding including hemorrhagic stroke, and bleeding from the urinary tract). The researchers also calculated a net clinical benefit defined as: Net clinical benefit = (ischemic stroke rate with no treatment – ischemic stroke rate with treatment) – 1.5 x (intracranial hemorrhage rate with treatment – intracranial hemorrhage with no treatment)
NOTE: The 1.5 multiplication factor for hemorrhagic stroke reflects the fact that hemorrhagic strokes are usually far more serious than are ischemic strokes.
During the first year following discharge from hospital, 5298 thromboembolic events were recorded among patients who had remained on their prescribed treatment for the entire year. Distribution of these events (%/year) according to CHADS2 and CHA2DS2-VASc scores was as follows: