AF without other CV comorbidities confers no elevated risk for stroke
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Atrial fibrillation alone with no other CV comorbidities conferred no greater risk for stroke compared with patients with neither AF nor CV comorbidities.
However, patients without AF but with CV comorbidities experienced an elevated risk for both stroke and cardioembolic stroke, according to findings from the REGARDS study published in the Journal of the American Heart Association.
Researchers classified 28,253 participants (mean age, 65 years; 55% women) into one of four groups based on the presence or absence of AF and the presence or absence of CV comorbidities.
They observed that participants with AF alone had no elevated risk for stroke compared with patients with neither AF nor CV comorbidities (HR = 1.23; 95% CI, 0.62-2.18).
“In this analysis of the REGARDS study cohort, we found no evidence of an increased risk of stroke among participants with AF without cardiovascular comorbidities, compared with the reference group of those with neither AF nor cardiovascular comorbidities,” Matthew J. Singleton, MD, MBE, MSc, MHS, of the section of cardiology at the Wake Forest School of Medicine, Winston-Salem, North Carolina, and colleagues wrote. “This finding was consistent in subgroup analyses. However, there was evidence of effect modification between age (< 64 vs. 64 years) and group. For those with cardiovascular comorbidities without AF, we found an increased risk of cardioembolic stroke, even in the absence of AF.”
In other findings, participants without AF but with CV comorbidities experienced an elevated risk for both stroke (HR = 1.77; 95% CI, 1.48-2.18) and cardioembolic stroke (HR = 2.34; 95% CI, 1.48-3.9) compared with those without AF or CV comorbidities.
“We feel that our study adds substantively to the existing literature owing to the size of the subcohort of participants with AF without cardiovascular comorbidities,” the researchers wrote. “In addition, our study is the first analysis of a large cohort of patients with AF without cardiovascular comorbidities that was able to adjust for race, education and income by utilizing a biracial nationwide prospective cohort in which there was formal adjudication of events from the medical record and long-term follow-up was available.”
Perspective
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Christine M. Albert, MD, MPH
Current guidelines do not recommend anticoagulation for patients with AF under age 65 that do not have any accompanying thromboembolic risk factors. This recommendation is based upon several population and cohort studies demonstrating very low risk for stroke in patients below the age of 65 who do not have evidence for structural heart disease or accompanying stroke risk factors.
Although strokes due occasionally occur in this subset of the population, the available data suggest that the risk for bleeding with oral anticoagulation likely outweighs the risk for stroke. However, the number of individuals with isolated AF in observational studies is small, limiting power to detect small increase in stroke risk. As a result, clinicians sometimes struggle with this recommendation, particularly in patients with persistent AF, since a stroke in a young healthy person is a devastating outcome.
The REGARDS study adds significantly to this literature as one of the largest observational studies to report on stroke risk among patients who have AF and no other comorbidities. In the subsample of 386 patients with AF and no comorbidities, the researchers identified 18 stokes, amounting to an incidence of 5.4 strokes per 1,000 person-years. The investigators found that after controlling for other patient characteristics and lifestyle habits, the risk for total stroke was not significantly elevated in the patients with AF and no comorbidities as compared to those without AF and no comorbidities. However, the researchers found that patients with AF but without comorbidities did have a higher risk for embolic stroke, the most common and devastating type of stroke in AF patients. This raises the concern that there could indeed be a small elevation in the risk of embolic stroke in these patients, but whether the benefits of anticoagulation would outweigh the risks with such a small incidence of embolic stroke would need to be proven in a clinical trial before guidelines could change. Also, since the data on comorbidities was self-reported and information on valvular heart disease was lacking, it is possible that undetected comorbidities might have been present in some of the patients designated as having no comorbidities. The authors also acknowledge that the diagnosis of AF might have increased the likelihood that their stroke would be attributed to an embolic source.
In summary, the data from this well done, large scale observational study are for the most part reassuring and consistent with prior studies suggesting that the risk for stroke in patients with AF but without comorbidities is low. To further advance our knowledge about this important subset of patients, large multicenter registries that enroll substantial numbers of these seemingly low-risk patients with longitudinal follow-up will be required.
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