Stroke risk based on classification of atrial fibrillation: real-world vs clinical trial

Abstract Background The most widely accepted clinical classification of atrial fibrillation (AF) is according to temporal rhythm-based patterns, reflecting the notion that most patients initially suffer from transient episodes that prolong over time due to atrial substrate remodelling as the disease progresses. Therefore, it may be speculated that patients with extended episodes of “continuous” AF (persistent, long-standing persistent and permanent AF) may be at higher risk of stroke complications compared to paroxysmal AF (pAF). However, the risk of stroke according to clinical classification of AF remains poorly defined. In this study, we assessed the impact of AF type on stroke risk in patients with AF from “real-world” and “clinical trial” cohorts. Methods Post-hoc analysis of patient-level data from the Murcia AF Project and AMADEUS trial. All patients were anticoagulated. Patients were grouped into those with pAF and non-pAF. pAF was defined as AF that terminates spontaneously or with intervention within seven days of onset. Non-pAF was defined as AF that lasted longer than seven days, including persistent, long-standing persistent and permanent AF subtypes. Study endpoint was the incidence rate of ischaemic stroke. A modified CHA2DS2-VAS“c” score that applied one additional point for a “c” criterion of continuous AF (i.e. non-pAF) was calculated. Results 5,917 patients were included; 1,361 (23.0%) real-world and 4,556 (77.0%) clinical trial. Real-world patients had a median age of 76 (interquartile range [IQR] 71–81) years with 51.3% females compared to a median age of 71 (IQR 64–77) years with 33.5% females among clinical trial participants. Baseline demographics were comparable in both groups in the real-world cohort but clinical trial participants with non-pAF were older, predominantly male and had more comorbidities compared to those with pAF. Crude stroke rates were comparable between the groups in real-world patients (incidence rate ratio [IRR] 0.72 [95% CI, 0.37–1.28], p=0.259) though clinical trial participants with non-pAF (vs. pAF) had a significantly higher crude rate of stroke events (IRR 4.66 [95% CI, 2.41–9.48], p<0.001). Using multivariable cox regression analysis, AF type was not independently associated with stroke risk in the real-world (adjusted hazard ratio [HR] 1.41 [95% CI, 0.80–2.50], p=0.239) and clinical trial (adjusted HR 1.17 [95% CI, 0.62–2.20], p=0.621) cohorts, after accounting for known risk factors using the CHA2DS2-VASc score. Using receiver operating characteristic curves analysis, we found no significant improvement in the CHA2DS2-VAS“c” compared to CHA2DS2-VASc score in either cohort (p>0.05). Conclusion Overall, there was no association between the temporal rhythm-based patterns of AF and stroke risk among anticoagulated patients, suggesting that this should not be a consideration when assessing the need for anticoagulation in AF. Funding Acknowledgement Type of funding sources: None.