Takabayashi K, Hamatani Y, Yamashita Y, Takagi D, Unoki T, Ishii M, et al. Incidence of Stroke or Systemic Embolism in Paroxysmal Versus Sustained Atrial Fibrillation: The Fushimi Atrial Fibrillation Registry. Stroke. 2015
Afib is a major risk factor for stroke, and oral anticoagulation (OAC) has been shown to be the most effective preventative treatment. Since OAC is associated with increased bleeding risk, efforts have been made to stratify risk by identifying patient characteristics which increase the risk of stroke in AFib patients (CHF, Hypertension, Age, Diabetes, etc.). Until recently, paroxysmal and persistent AFib were reported to have the same associated risk of thromboembolic events, and the guidelines recommend OAC treatment for prevention, regardless of the type of AFib. It does seem intuitive that someone in constant AFib for years would have a higher risk of stroke than a patient who had half an hour of AFib after surgery. Several recent studies have shown a lower stroke rate in paroxysmal AFib compared to sustained AFib. There is also limited data in Asian patients, so some equipoise existed which prompted this study.
Data was obtained from the Fushimi AF Registry, whose only inclusion criteria was the documentation of AF on a 12-lead EKG or Holter monitoring at any time. Paroxysmal AF was defined as lasting under 7 days; persistent AF lasted longer than 7 days was but able to be terminated by medication or electrical cardioversion; permanent AF was refractory to medical or electrical cardioversion. Persistent and permanent AF were combined in this study as SAF (sustained AF), due to difficulty differentiating these in daily clinical practice. Multivariate analyses were performed for the vascular risk factors in both the CHADS2 and CHA2DS2-VASc scores, and also included the variable of “low body weight” (which was shown to correlate with stroke risk in Japanese AF patients).
3304 patients were included, split about evenly between paroxysmal and sustained AF. PAF patients were younger, more often symptomatic (palpitations), and less likely to have a history of stroke, CHF, or CKD. The CHADS2/CHA2DS2-VASc scores were lower in PAF patients, and there was a lower rate of OAC use among PAF patients at any age or CHADS2 score compared to SAF patients. About 10 percent of PAF patients progressed to SAF, and there was a significantly higher rate of stroke/systemic embolism among those who progressed compared to those who did not. PAF patients had lower risk of stroke/systemic embolism overall, and this persisted when the patients were stratified by OAC use and CHADS2 score. On multivariate analysis, PAF was an independent risk factor for a reduced risk of stroke/systemic embolism, while age ≥75 and history of stroke portended increase risk. PAF remained significant even when CHADS2 and CHA2DS2-VASc criteria were added to the model, as well as when age was added as a continuous variable. Low body weight (≤50kg) was indeed an independent risk factor for increased risk of stroke/systemic embolism.
This study did not measure the AFib burden, which may be the key to risk stratification in AFib. The other Asian registry mentioned, J-RHYTHM, did not enroll patients who maintained sinus rhythm for over a year, while this registry did. J-RHYTHM showed more thromboembolism in SAF patients, but this difference disappeared after adjusting for vascular risk factors. Neither registry used long-term monitoring or included AF burden as a variable. In this study, patients with PAF were more likely to receive anti-arrhythmic drugs or catheter ablation, which may have decreased AF burden and stroke risk.
In order for these results to influence the guidelines on treatment of PAF, it would have been important to compare the anticoagulated PAF to non-anticoagulated PAF, as well as to age and risk-matched non-AFib patients. However, since this was a registry, it is difficult to make a comparison between treated and untreated patients as there are other contributing factors which influence the initiation of OAC. This can be seen here, as the incidence rate of stroke/systemic embolism per 100 person-years in OAC-treated patients is higher than in untreated patients (and this difference persists for ischemic stroke).
The discrepancies between PAF and SAF shown in this observational registry study are important and may lend evidence to the idea that AF burden is associated with stroke risk. As monitoring technology advances, we are identifying PAF earlier and more often (and committing patients to OAC sooner), but we also have the capability to quantify the AFib burden. Despite guidelines recommending OAC for PAF, only 39% of patients in this registry were prescribed OAC. So, it would be ethical to perform a study of PAF patients which quantifies AFib burden (via wearable or implanted monitor) and randomizes those with low vascular risk scores and a low AF burden to antiplatelet therapy. This would be very useful in creating safe and evidence-based recommendations on the need for OAC therapy in PAF patients.