A retrospective registry analysis in Sweden found patients with nonvavular atrial fibrillation who were treated with warfarin had an annual incidence of 2.19 percent for all-cause mortality and 0.44 percent for intracranial bleeding.

The rates were lower than those observed in pivotal studies of novel anticoagulants. However, the researchers noted that patients taking warfarin should be monitored if they have renal failure, concomitant aspirin use and an individual therapeutic range less than 70 percent or high internationalized normalized ratio (INR) variability.

Lead researcher Fredrik Björck, MD, of Umeå University in Sweden, and colleagues published their results online in JAMA Cardiology on April 20.

The researchers analyzed 40,449 patients who enrolled in a retrospective, multicenter cohort study. They were identified from national registries in Sweden, including AuriculA, a national quality register for atrial fibrillation and oral anticoagulation. AuriculA includes more than 126,000 patients from 224 specialized anticoagulation clinics and primary healthcare centers in Sweden.

Of the patients, 40.0 percent were women. At baseline, the mean age was 72.5 years old and the mean CHA2DS2-VASc score was 3.3.

There was no diagnosis recorded in the Swedish National Patient Register for 27.9 percent of patients, which the researchers said meant the patients received warfarin in primary healthcare settings with no prior hospital visit. For those patients, there was no background data available.

For patients receiving concomitant aspirin therapy, the annual rate of major bleeding was 3.07 percent and the annual rate of thromboembolism was 4.90 percent. The researchers mentioned patients with renal failure had an increased risk of intracranial bleeding.

For patients with an individual therapeutic range less than 70 percent, the annual rates of major bleeding and thromboembolism were 3.81 percent and 4.41 percent. For patients with high INR variability, the rates were 3.04 percent and 3.48 percent, respectively.

The mean individual therapeutic range was 68.6 percent, which was higher than the 55.2 percent to 64.9 percent found in studies involving apixaban, dabigatran, edoxaban and rivaroxaban.

“Our results support previous findings of higher risk of major bleeding when warfarin is combined with aspirin, with a significantly higher annual incidence of any major bleeding, gastrointestinal tract bleeding, and other major bleeding compared with when no additional antiplatelet drugs are used with warfarin,” the researchers wrote. “The baseline data showed overrepresentation of cardiovascular disease in the aspirin group compared with the group receiving only warfarin, and our findings of a high incidence of thromboembolic events in the aspirin group are, therefore, as expected.”

The researchers cited a few limitations of the study, including its retrospective observational design and the fact that it did not include a comparator group of patients receiving other treatments. In addition, this study was limited to patients in Sweden, which is a high-income country with a decreasing stroke rate. Thus, the findings may not be generalizable to other countries or ethnic groups.

They added that it was difficult comparing results and event rates between this study and other novel anticoagulant trials because they had different populations, data collection methods and event definitions.