Stroke Rounds: Afib Stroke Predictor May Overestimate Risk for Some

CT scan slice of the brain showing a right-hemispheric ischemic stroke. (Courtesy Wikipedia.)

Atrial fibrillation patients with a CHA₂DS₂-VASc score of 1 have a lower than reported risk for ischemic stroke and are not likely to benefit from anticoagulation therapy, researchers found.

Findings from a study of atrial fibrillation (AF)-related stroke risk in this population highlight important limitations of the CHA₂DS₂-VASc scoring system, researcher Leif Friberg, MD, PhD, of the Karolinska Institute in Stockholm, and colleagues wrote in the Journal of the American College of Cardiology, published online Jan. 21.

"The risk of ischemic stroke among patients with AF and a CHA₂DS₂-VASc score of 1 seems to be lower than previous studies have indicated," they wrote. "This earlier finding may have led to unnecessary, and potentially harmful, oral anticoagulant (OAC) treatment of low-risk patients."

OAC Use Common in Low-Risk Patients

Oral anticoagulant treatment is recommended for AF patients on the basis of ischemic stroke risk, and guidelines in both Europe and the U.S. advocate use of the CHA₂DS₂-VASc stroke risk scoring system, in which risk is assessed based on the presence of congestive heart failure (C), hypertension (H), age ≥75 (A₂), diabetes mellitus (D), stroke/transient ischemic attack history (S₂), vascular disease (V), age 65-74 years (A) and sex category (Sc).

The maximum CHA₂DS₂-VASc score is 9, with age 75 and over and history of stroke or TIA scoring 2 points and all other risk factors scoring 1 point. Consequently, patients with a score of 1 have just one risk factor and it's of the lesser grade.

According to Friberg and colleagues, stroke risk estimates for Afib patients with CHA₂DS₂-VASc scores of 1 who are not treated with OACs vary by a factor of 3 in different studies, from a low of 0.6% to greater than 2%.

"At an annual unprotected risk of 0.6% it is unlikely that patients will realize the benefits of treatment, whereas patients with an annual risk of >1% are more likely to benefit from treatment," the researchers wrote.

The goal of the study by Friberg and colleagues was to better understand the risk of stroke related to Afib among patients not treated with an OAC with a CHA₂DS₂-VASc score of 1.

The retrospective study of patients enrolled in nationwide, cross-matched Swedish health registries included 140,420 patients with Afib identified over a 5-year period. Patients were excluded if they had valvular AF or if they had been exposed to the drug warfarin within 6 months of the index data or study period.

Women Scoring 1 Have Very Low Stroke Risk

Using a wide stroke diagnosis (including hospital discharge diagnoses of ischemic stroke as well as unspecified stroke, transient ischemic attack, and pulmonary embolism) yielded a 44% higher annual risk than was seen when only ischemic stroke was used as the endpoint.

Including stroke events in conjunction with the index hospitalization for AF doubled the long-term risk beyond the first 4 weeks.

The annual event rates in the Swedish National Patient Register varied between 0.5% and 0.9% among patients with a CHA₂DS_2-VASc score of 1, depending on whether only ischemic strokes were the sole endpoint or a more inclusive one was used and the event rate dropped to 0.3% in the Swedish stroke register, Riks-Stroke.

"European guidelines are clear that women with a CHA₂DS₂-VASc score of 1 should not be given anticoagulation therapy on the basis of their sex alone; the risks of men and women with CHA₂DS₂-VASc scores of 1 were therefore assessed separately," the researchers wrote. "Indeed, we found that women were truly low risk, with an annual ischemic stroke rate of only 0.1% to 0.2%. For men, the ischemic stroke rate was 0.5% according to Riks-Stroke and 0.7% according to the National Patient Register."

When diagnoses of TIA, pulmonary embolism, arterial embolism, and stroke (type not specified) were considered, the annual event rate for men was 1.3%.

Half of Low-Risk Men Receiving OAC Treatment

When the researchers cross-matched the National Patient Register with the Dispensed Drug Register, they found that 46.2% of the men and 22.5% of the women with a CHA₂DS₂-VASc score of 1 had taken warfarin or some other OAC and that warfarin use was more common among these patients than among patients with scores of 3 or higher.

"European guidelines favor OAC treatment at CHA₂DS₂-VASc scores of 1, whereas the newly adopted U.S. guidelines recommend treatment from 2 points or higher, with an option to treat with OAC, aspirin, or nothing at 1 point," the researchers wrote. "Our results indicate that the European recommendation for OAC treatment at CHA₂DS₂-VASc score of 1 may be unwise."

In an editorial published with the study, Daniel E. Singer, MD, of Massachusetts General Hospital and Harvard Medical School, and Michael D. Ezekowitz, MBChB, DPhil, of Thomas Jefferson University in Philadelphia, agreed that Afib patients younger than age 65 with CHA₂DS₂-VASc scores of 1 are unlikely to benefit from anticoagulation therapy.

"Going forward, guideline writers should be aware of the drawbacks of the CHA₂DS₂-VASc score," they wrote. "They should focus on absolute rates of stroke corresponding to risk prediction point scores and be alert to potential biases in studies reporting these rates."

They added that research is needed to "harmonize method for analyzing large AF databases," and suggested that treatment recommendations should reflect variations in reported rates of stroke risk.

"Trials of newer anticoagulant agents versus placebo in the lowest-risk AF patients would greatly inform these recommendations," they added.

From the American Heart Association:

• 2014 AHA/ACC/HRS Guideline for the Management of Patients With AFib
• Guidelines for the Prevention of Stroke in Women

The research was funded by the Swedish Heart and Lung Foundation, the Stockholm County Council, the Swedish Society of Medicine and the Board of Benevolence of the Swedish Order of Freemasons.

Researcher Leif Friberg, MD, PhD, reported receiving research grants or lecture fees (not related to this research) from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Sanofi, and St. Jude Medical. Researcher Andreas Terent, MD, PhD, reported receiving research grants from AstraZeneca.

• Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Primary Source

Journal of the American College of Cardiology

• Source Reference: Friberg L, et al "Benefit of anticoagulation unlikely in patients with atrial fibrillation and a CHA₂DS₂-VASc score of 1" JACC 2015; 65225-232.

This article was first published on MedPage Today and reprinted with permission. (Free registration is required.)