AF Patients Taking Oral Anticoagulants Have Milder Strokes

Daniel M. Keller, PhD

December 11, 2012

Brasilia, Brazil — In study of stroke patients with atrial fibrillation (AF), those who were receiving oral anticoagulant therapy (OAT) at the time of the stroke had less severe stroke, shorter hospital stays, and lower 30-day mortality than patients not receiving OAT.

Søren Johnsen, MD, PhD, from the Department of Clinical Epidemiology at Aarhus University Hospital in Aarhus, Denmark, said that even though AF is a major risk factor for ischemic stroke and oral anticoagulation is an effective prophylaxis against cardioembolic stroke (as has been seen in other reports), only a minority of the acute stroke patients with AF in this study were receiving it at the time of the stroke.

The findings were presented here at the 8th World Stroke Congress (WSC).

Lower Stroke Severity and Mortality

If preadmission OAT is causally related to less severe stroke and better outcomes, as has been reported previously, it would be a strong argument for making sure that patients with AF receive appropriate OAT, the authors note. However, previous studies have been limited by small sample sizes, a low proportion of OAT users, inclusion of primarily ischemic strokes, and concerns about possible confounding.

Drawing on several Danish national databases that track patients, diagnoses, treatments, prescriptions, vital status, and more, the investigators designed a nationwide, population-based follow-up study of all Danish patients hospitalized with acute stroke and AF from 2003 to 2009. Preadmission OAT use was defined as having filled at least 1 OAT prescription within the previous 90 days before admission.

Of a total cohort of 11,356 stroke patients with AF, 2492 (21.9%) used OAT. Stroke severity was judged according to the Scandinavian Stroke Scale, in which a score less than 30 at the time of admission indicated a severe or very severe stroke. Overall, 28.3% of OAT users had a severe stroke vs 36.5% of the non-OAT group (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.64 - 0.84).

OAT use was significantly associated with lower severity of ischemic stroke (OR, 0.67; 95% CI, 0.57 - 0.78) but not severity of intracerebral hemorrhage. OAT was also associated with lower severity in the older age groups of 70 to 79 years and 80 years and older.

Stroke severity also correlated with the degree of anticoagulation. Compared with no OAT (reference OAT, 1.00), an international normalized ratio (INR) less than 2.00 was associated with a nonsignificant stroke severity OR of 0.88 (95% CI, 0.61 - 1.26).

However, an INR of 2.00 to 3.00 or greater than 3.00 was associated with significant decreases in stroke severity of 48% and 42%, respectively (INR, 2.00 - 3.00: OR, 0.52 [95% CI, 0.37 - 0.75]; INR greater than 3.00: OR, 0.58 [95% CI, 0.37 - 0.90]).

Hospital length of stay was shorter with higher INR. The OR of the relative length of stay adjusted for quality of in-hospital stroke care with an INR of 2.00 to 3.00 was 0.80 (95% CI, 0.66 - 0.98); with an INR greater than 3.00, it was 0.69 (95% CI, 0.54 - 0.89).

The OR adjusted for 30-day mortality among patients with any form of stroke during OAT was 0.84 (95% CI, 0.72 - 0.98), and in patients with ischemic stroke the adjusted OR was 0.70 (95% CI, 0.58 - 0.84). However, the OR among patients with intracerebral hemorrhage was not statistically significant. Compared with no OAT, the 30-day mortality was not significantly associated with any INR values for the patients taking OAT.

More Bleeding Episodes Offset by Better Outcomes

Dr. Johnsen said that of the patients receiving preadmission OAT, the proportion of those with intracerebral hemorrhage was 4 times that (20%) of patients not receiving OAT (5%).

"So there were more bleeds among the OAT users," he told Medscape Medical News. "However, if you looked at the overall outcome of the patients, including stroke severity, length of stay, and mortality, the patients receiving OAT came out on top in all these outcomes, even though they had more bleeds. And some of this was driven by a particularly good prognosis of the ischemic stroke patients."

The 20% of patients with intracerebral hemorrhage while receiving OAT had a shorter length of stay than the ones not receiving OAT, "which was probably driven by a higher in-hospital mortality rate," he said. Mortality data suggested that OAT use was associated with a poorer prognosis in the case of intracerebral hemorrhage compared with nonuse of OAT, although this did not reach statistical significance.

Nonetheless, on the basis of CHA2DS2-VASc scores measured just before patients' strokes, Dr. Johnsen said that "well over 90%" of them had scores of greater than 2, making them candidates for OAT, compared with the 21.9% actually receiving OAT.

Some AF was diagnosed only upon stroke admission, but even for patients with known AF and a high CHA2DS2-VASc score before admission, fewer than 1 in 3 was receiving OAT, "so there was really strong indications of under use," he said. "In patients with a high CHA2DS2-VASc score above 2, you would say that is normally an indication of using OAT unless there are some very strong contraindications."

Reluctance for Treatment

Ralph Sacco, MD, MS, professor and chairman of the Department of Neurology at the University of Miami Miller School of Medicine in Florida and past president of the American Heart Association, commented to Medscape Medical News that undertreatment of patients with AF is still common.

"I still think there are too few patients with good indications for oral anticoagulant therapy who are treated, and remember, this still in the age of just now new oral anticoagulants hitting the shelves," Dr. Sacco said.

He said the proportion of patients observed to be treated with OAT in the study are probably typical of the use of OAT and probably mainly reflect the use of warfarin. "We have known for years that there is a reluctance by physicians to use warfarin. There is a reluctance for patients to take warfarin because of the bleeding risk and the need for monitoring drug-drug interactions [and] drug-diet interactions that make warfarin more difficult to use.

"All of our evidence-based guidelines give oral anticoagulants class 1, grade A evidence that they should be used for stroke prevention, and I think we still too often see that they are underutilized," Dr. Sacco concluded.

Dr. Johnsen is on the advisory board of and has received research grants from Bristol-Myers Squibb, which supported this study. He has received speakers' fees from Pfizer. Dr. Sacco was not involved in the study and has disclosed no relevant financial relationships.

8th World Stroke Congress (WSC). Abstract 921. Presented October 12, 2012.