Stroke Risk Lower in Atrial Flutter Than Atrial Fibrillation

Patients with atrial flutter (AFL) have a significantly lower risk for ischemic stroke than do patients with atrial fibrillation (AF), new research suggests.

A team of Taiwanese investigators compared older adults with AF and AFL, stratified by CHA₂DS₂-VASc score, to matched controls without these conditions and found that those with AF had significantly higher risk for ischemic stroke, heart failure hospitalization, and all-cause mortality than did those with AFL and controls.

Patients with AFL had significantly higher risk for heart failure hospitalization and all-cause mortality than controls, but the incidence of ischemic stroke was significantly higher only at a CHA₂DS₂-VASc score of 5 to 9.

"Interestingly, our study showed that the incidence of ischemic stroke at a CHA₂DS₂-VASc score of 1 in the AF cohort was similar to a CHA₂DS₂-VASc score of 2 in the AFL cohort, and the incidence of ischemic stroke at a CHA₂DS₂-VASc score of 2 in the AF cohort was similar to a CHA₂DS₂-VASc score of 4 in the AFL cohort," investigators Yu-Sheng Lin, MD, from the Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, and Mien-Cheng Chen, MD, from the Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan, told theheart.org | Medscape Cardiology in an e-mail.

"Therefore, our study suggests that further research should be done to evaluate the net clinical benefit of oral anticoagulants to prevent ischemic stroke in patients with AFL, according to the currently recommended level of the CHA₂DS₂-VASc score," they conclude.

The study was published online August 3 in JAMA Open.

Different Risk, Same Threshold

AFL and AF are "often grouped together" in terms of stroke risk stratification, although the incidence of stroke with AFL is much lower than that with AF, the authors write.

While AFL and AF share many common risk factors for occurrence, differences in clinical outcomes have been reported in previous studies.

Pharmacologic management of AFL is usually considered to be the same as for AF, particularly in preventing thromboembolic events, with the CHA₂DS₂-VASc score as the current standard scoring system for risk stratification.

"Small observational studies reported that the incidence of ischemic stroke in solitary AFL patients was lower, compared to solitary AF patients," Lin and Chen said.

"Additionally, electrophysiological mechanisms were different between AF and AFL— randomly multiple micro- or macro-re-entrant activation wavelets with atrial rate ≥ 350 beats per minute exist in AF, while macro-re-entrant atrial tachycardia with atrial rate usually between 250 and 350 beats per minute exist in AFL," they noted.

Despite these differences, the 2016 European Society of Cardiology guideline recommends that in both AFL and AF, anticoagulation should be prescribed for patients with a CHA₂DS₂-VASc score of 2 or greater and non–vitamin K oral anticoagulants should be considered in patients with a CHA₂DS₂-VASc score of 1 or greater.

"The question is why the preventing ischemic stroke strategy [in AFL] should be managed with the same threshold as that in AF patients, especially in the absence of large randomized studies or large registry database," Lin and Cheng said.

"Accordingly, we conducted this nationwide cohort study analyzing data from the Taiwan National Health Insurance Research Database during a 12-year observation period to investigate differences in clinical outcomes between AF, AFL, and matched control cohorts," they reported.

The researchers compared patients with AF (n = 188,811; mean [standard deviation] age, 73.8 [13.4] years; 55.5% male) to patients with AFL (n = 6121; mean age, 67.7 [15.8] years; 61.0% male) and a matched control cohort (n = 24,484; mean age, 67.3 [15.6] years; 61.0% male).

Patients were stratified by CHA₂DS₂-VASc score, a risk calculation taking into account such factors as congestive heart failure, hypertension, age 75 years or older, diabetes, stroke, vascular disease, age 65 to 74 years, and sex.

Patients with concomitant AF and AFL diagnoses were excluded. Patients who received therapy that might have affected study outcomes (eg, radiofrequency catheter ablation and anticoagulation) were also excluded.

When to Consider Anticoagulants

Compared with the patients with AFL and the control participants, patients with AF were older, were more predominantly female, and had higher CHA₂DS₂-VASc scores.

Moreover, the AF cohort had a significantly higher prevalence of comorbidities (eg, diabetes, hypertension, and dyslipidemia, as well as history of stroke), compared with the other two cohorts.

The incident density (ID) — ie, events per 100 person-years — of ischemic stroke in the AF cohort was 3.08 (95% confidence interval [CI], 3.03 - 3.13) vs 1.45 (95% CI, 1.28 - 1.62) in the AFL cohort and 0.97 (95% CI, 0.92 - 1.03) in the control cohort.

The IDs of HF hospitalization were 3.39 (95% CI, 3.34 - 3.44) in the AF cohort compared with 1.57 (95% CI, 1.39 - 1.74 and 0.32 (95% CI, 0.29 - 0.35) in the AFL and control cohorts, respectively.

The IDs of all-cause mortality were likewise significantly higher in the AF cohort (17.8 [95% CI, 17.7 - 17.9]) than in the AFL and control cohorts (13.9 [95% CI, 13.4 - 14.4] and 4.2 [95% CI, 4.1 - 4.4], respectively).

Compared with the matched control cohort, the incidences of heart failure hospitalization and all-cause mortality in the AFL cohort were significantly higher across all levels. However, the incidence of ischemic stroke was significantly higher only at CHA₂DS₂-VASc scores of 5 to 9.

Compared with the AFL cohort, the incidences of ischemic stroke and heart failure hospitalization in the AF cohort were significantly higher at a CHA₂DS₂-VASc score of 1 or greater. In contrast, the incidence of all-cause mortality was significantly higher only at CHA₂DS₂-VASc scores of 1 to 3.

The authors suggest that differences in comorbidities among the three groups may have resulted in different clinical outcomes by contributing to the different degrees of atrial myopathy, endocardial remodeling, and neurohumoral activation.

They also suggest that, on the basis of their findings, patients with AFL may be prescribed anticoagulants when the CHA₂DS₂-VASc score is 4 or greater (with an ID of 2.3%) and non–vitamin K oral anticoagulants when the CHA₂DS₂-VASc score is 2 or greater (with an ID of 1.0%).

However, because the incidences of ischemic stroke in the AF cohort across all levels of CHA₂DS₂-VASc scores and in the AFL cohort at a CHA₂DS₂-VASc score of 5 to 9 were both significantly higher than in the control cohort, oral anticoagulants should be considered for patients with AFL and patients with AF when the CHA₂DS₂-VASc score is 5 or greater.

Risk-Benefit Calculation

Commenting on the study for theheart.org | Medscape Cardiology, Subbarao Choudry, MD, assistant clinical professor, Cardiac Arrhythmia Service, Icahn School of Medicine, Mount Sinai, New York City, who was not involved in the study, said he was not surprised by the findings but cautioned that they "must be put into context."

He noted that the researchers "carefully selected patients with only AFL over a long time period" but "a large number of patients who present with AFL either have concomitant AF or go on to develop AF during follow-up," which "decreases the clinical utility of the study."

He commented that the "take-home message from this to practicing clinicians is that in patients who only have AFL, the risk of stroke seems to be lower than for those with AF."

Thus, "while this study alone should not be used to guide therapy, it may change the risk-benefit calculation for oral anticoagulation in those patients who only have AFL, have a relatively low CHA₂DS₂-VASc score, and are at increased risk of bleeding," he said.

Lin and Chen emphasized that the "efficacy and safety of oral anticoagulants to reduce ischemic stroke in patients with AFL with the currently recommended CHA₂DS₂-VASc in those patients who only have AFL and have a relatively low CHA₂DS₂-VASc score should be reevaluated."

This study is based in part on National Health Insurance Research Database data provided by the Applied Health Research Data Integration Service from the National Health Insurance Administration. The authors and Choudry have disclosed no relevant financial relationships.

JAMA Network Open. Published online August 3, 2018. Abstract

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