Stroke prevention in patients with atrial flutter: many questions still unanswered

This editorial refers to ‘Clinical outcomes of solitary atrial flutter patients using anticoagulation therapy: a national cohort study’ by Y.-L. Chen et al., on pages 313--321. Atrial flutter (AFL) often coexists with or precedes atrial fibrillation (AF), but the prevalence rate is lower.1 Although AF and AFL share some common risk factors, the pathogeneses of these two diseases are different. The initiation and maintenance of AF usually involved the pulmonary veins and arrhythmogenic substrate in the left atrium, and differently, the re-entry circuit of typical AFL is located in the right atrium. Similar to AF, stroke prevention is central to the management of AFL. The 2016 AF guidelines of European Society of Cardiology stated that ‘for patients with AFL, antithrombotic therapy is recommended according to the same risk profile used for AF’.2 However, one may question whether we have enough data to guide the use of oral anticoagulants (OACs) for AFL patients similarly since the risk of ischaemic stroke associated with AFL may not be as high as AF.3 In the study by Chen et al.,4 the authors analysed and compared clinical outcomes among patients with solitary AFL, solitary AF, and AFL developing AF thereafter. The authors demonstrated that the risk of ischaemic stroke and major bleeding was lower for patients with solitary AFL compared with those with solitary AF or AFL with late occurrence of AF. Most importantly, the best net clinical outcome with warfarin was observed for solitary AFL patients with a CHA2DS2-VASc score ≥4. This finding suggests that the threshold of the CHA2DS2-VASc score to initiate OACs for AFL patients is higher than that for AF patients. The authors should be congratulated on their interesting and important work, which provide useful data to help decision making about the initiation of OACs in patients with AFL. However, several issues remained unsolved. The authors did not report international normalized ratio and time in therapeutic range (TTR) for warfarin, because these data were lacking in the Taiwan registry database. In the Randomized Evaluation of Long-Term Anti-coagulation Therapy (RE-LY) trial, the TTR for warfarin was only 44% in Taiwan.5 Since a higher TTR is significantly associated with a lower risk of ischaemic stroke and intracranial haemorrhage for AF patients receiving warfarin,6 warfarin may be able to provide a positive net clinical benefit for AFL patients with a CHA2DS2-VASc score <4 if the quality of warfarin use could be improved. Moreover, non-vitamin K antagonist OACs (NOACs) were not available during the study period in Taiwan, and therefore, it is unclear whether the findings of this study could be generalized to NOACs. According to the previous analysis performed by Eckman et al.,7 the ‘tipping point’ for the use of NOACs for stroke prevention would be around 0.9% per year. As Chen et al. have indicated in their work, the annual risk of ischaemic stroke is higher than 0.9% for solitary AFL patients with a CHA2DS2-VASc score ≥2. It may suggest that NOACs could be considered for solitary AFL patients with a CHA2DS2-VASc score ≥2, which is similar to the treatment threshold of AF patients. Another uncertain issue is about the stroke prevention strategy for AFL patients receiving catheter ablation, the Class I recommendation for the treatment of AFL.2 Given the lower recurrence rate of AFL after successful cavotricuspid isthmus ablation compared with AF,8 the decision about the prescription of long-term OACs is even more difficult and probably less applied in daily practice. One of the important reasons to continue OACs for patients with AFL despite a successful ablation is the concern of the close association of these two diseases, either the under-detection of AF when AFL was first diagnosed or occurrence of new-onset AF after catheter ablation of AFL. The previous study has demonstrated that incident AF occurred among 22% of AFL patients after ablation, and the left atrial diameter was identified as the only predictor of AF.9 Therefore, we would rather have to keep OACs for AFL patients after successful AFL ablations unless we can be sure about who would not get new AF in the future. Similarly, although the authors suggested a higher CHA2DS2-VASc score to initiate OACs for ‘solitary AFL’ patients, we do not know which AFL patients had undetected AF or who will experience new-onset AF years later. It means that we would not know which patients are really ‘solitary AFL’. Since ischaemic stroke could be the first presentation of AF, delaying prescription of OACs for ‘solitary AFL’ patients until new-onset AF occur may expose some patients to the risk of ischaemic stroke which could be effectively prevented. However, the results of the present work added to some previous ones quite convincingly indicate that the risk of stroke in patients with AFL (widely treated with ablation of cavotricuspid isthmus in its typical form) is slightly lower than that for AF patients, let’s say around one point lower for a given strata of the CHA2DS2-VASc score.10 Future guidelines will thus have to indicate whether one may omit OAC for AFL patients in which it is sometimes debated in case of AF, particularly those with CHA2DS2-VASc score of 1 in males and 2 in females.2,11–13 Overall, this study nicely provides some unique data, but more studies, especially prospective and randomized interventional ones, are necessary to address uncertain issues. Clearly, there is much to learn about stroke prevention in AFL. Conflict of interest: L.F. has been a consultant or speaker for Bayer, Boehringer, BMS/Pfizer, Livanova, Medtronic and Novartis.