Stratifying Stroke Risk in Atrial Fibrillation: Beyond Clinical Risk Scores

Shadi Yaghi, MD; Hooman Kamel, MD


Stroke. 2017;48(10):2665-2670. 

In This Article

Prediction of Stroke Risk Based on Electrocardiographic Markers

Type of AF

There is conflicting evidence on whether stroke risk varies based on the type of AF. In the ACTIVE W trial (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events), which enrolled 6706 patients and compared anticoagulant therapy versus the combination of aspirin and clopidogrel, the risk of stroke or systemic embolism was similar in patients with paroxysmal as compared with persistent AF (RR, 0.87; 95% CI, 0.59–1.30).[28] More recently, an analysis of data from the ENGAGE trial (Edoxaban Versus Warfarin in Patients With Atrial Fibrillation) showed that the risk of stroke or systemic embolism was significantly lower in patients with paroxysmal AF (1.49% per year) when compared with persistent AF (1.83% per year) or permanent AF (1.95% per year).[29] A meta-analysis including 99 996 patients in 12 studies found that the rate of thromboembolism was higher in patients with nonparoxysmal AF as compared with those with paroxysmal AF (HR, 1.38; 95% CI, 1.19–1.61).[30] Overall, there is a growing consensus that the risk of thromboembolism increases as patients progress from paroxysmal to sustained to permanent AF.

Duration of AF

Studies investigating the association between these subclinical episodes of AF and stroke have yielded mixed results. The AFFIRM study (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) randomized 4060 patients with AF to rate- versus rhythm-control strategies. After 5 years of follow-up, the stroke risk among the 481 patients (12%) with asymptomatic AF was similar to the stroke risk in the remaining patients with symptomatic AF (3.8% versus 4.4%; P=0.52).[31] However, because only 4% of asymptomatic AF episodes were of <6-hour duration, no conclusions can be made on stroke risk in patients with brief episodes of AF.

Several studies investigated stroke risk in relation to the duration of AF. The ASSERT study (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) enrolled 2580 patients ≥65 years of age with hypertension and no known history of AF who had recently undergone pacemaker or defibrillator implantation. During the first 3 months after device implantation, subclinical atrial tachyarrhythmias lasting at least 6 minutes were captured in 261 (10.1%) patients, and these were associated with increased stroke or systemic embolism risk during a mean follow-up of 2.5 years (HR, 2.49; 95% CI, 1.28–4.85). Similarly, the SOS AF study (Stroke Prevention Strategies), which included 10 106 patients with implanted cardiac devices who underwent at least 3 months of follow-up, found an association between AF episodes of duration 5 minutes or longer and stroke (HR, 1.76; 95% CI, 1.02–3.02).[32] There seemed to be a proportional relationship between AF burden and stroke risk (HR per hour of AF duration, 1.03; 95% CI, 1.00–1.05; P=0.04).[32] On the contrary, the RATE study (Rate Control Therapy Evaluation in Permanent Atrial Fibrillation), which included 5379 patients with pacemakers and a mean follow-up period of 22.9 months, found that patients with episodes of AF <20 seconds duration had a similar risk of stroke or TIA compared with patients with no AF (HR, 0.87; 95% CI, 0.58–1.31). On the contrary, episodes of AF ≥20 seconds were associated with stroke or TIA (HR, 1.51; 95% CI, 1.03–2.21).[33] A common limitation of these studies is that patients included were already at high risk for AF and perhaps stroke because of the confounding cardiac diseases that necessitated implantation of such devices. Therefore, it is difficult to extrapolate this result to a wider population.

Anticoagulation therapy has been proven to reduce stroke risk in patients with a sufficient burden of AF to have it detected by pulse palpation or 12-lead ECG at multiple points in time.[34] However, it is uncertain whether anticoagulation reduces stroke risk in patients with brief and infrequent runs of subclinical AF. The ARTESiA trial (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation, NCT01938248), for example, aims to enroll 4000 patients with device-detected AF last 6 minutes to 24 hours and randomly assigns them to apixaban or aspirin and determines whether anticoagulation reduces the risk of ischemic stroke and systemic embolism in this population.