Reduction of stroke and mortality in patients with atrial fibrillation by catheter ablation? Finally, tackling the hard endpoints

This editorial refers to ‘Successful catheter ablation reduces the risk of cardiovascular events in atrial fibrillation patients with CHA2DS2-VASc risk score of 1 and higher’ by Y.-J. Lin et al., on page 676 ‘Will catheter ablation of atrial fibrillation help me live longer and protect me against stroke?’ patients with this arrhythmia quite frequently ask when the pros and cons as well as alternatives of this approach are being discussed. We are living in an era where catheter ablation is an increasingly used treatment for atrial fibrillation (AF).1 In general, catheter ablation should be considered for patients with AF who remain symptomatic despite optimal medical therapy, including rate and rhythm control. Whether to undertake an ablation procedure in a symptomatic patient should take into account the following: (i) the stage of atrial disease (i.e. AF type, left atrial size, AF history), (ii) the presence and severity of underlying cardiovascular disease, (iii) potential treatment alternatives (antiarrhythmic drugs, rate control), and (iv) patients' values and preference. According to the 2012 focused update of the ESC Guidelines on management of AF, ablation should even be considered as a first-line therapy in patients with symptomatic, AF and no or minimal heart disease AF.2 Moreover, ablation as adjunct therapy in patients with AF and heart failure treatment is on the horizon.3 What can the patient expect from this procedure? On the one hand, ablation is clearly superior to antiarrhythmic drug therapy with respect to freedom from recurrent AF, which can be achieved in 65–85% patients undergoing ablation, depending on patient characteristics, ablation approaches, and the duration of follow-up.1,3 Consequently, AF-related symptoms are reduced and quality of life as well as functional status are improved. On the other hand, there are severe, potentially life-threatening complications related to this invasive treatment, such as pericardial tamponade, stroke or thromboembolism (TE), pulmonary vein stenosis, or oesophageal perforation that can add up to a 3–5% complication rate associated with ablation.3 In addition, more than one ablation procedure is needed to achieve clinical improvement in a substantial proportion of patients.1,3,4 Currently, there are insufficient data on long-term effects of ablation on mortality and risk of stroke. Consequently, the physician's answer to the patient's question is ‘we do not know’—‘yet’ we may add as there are some promising studies available and large randomized trials are ongoing. Indeed, we have seen a significant improvement of our knowledge on this topic over the last 6 years. First, Oral et al.5 who retrospectively analysed 755 patients undergoing AF ablation and compared their freedom from TE with results of the Framingham cohort without AF, have demonstrated that during follow-up of 2 years patients after having had successful catheter ablation are at the same risk for stroke as patients without AF. Other studies have reported data on the incidence of stroke or TE in patients with low6 or moderate to high stroke risk7,8 and different anticoagulation protocols (e.g. aspirin vs. warfarin). Overall, the risk of stroke or TE was low and independent of the anticoagulation protocol. This led to the suggestion that aspirin can be used alone in selected patients after successful ablation. Of note, current guidelines strongly recommend warfarin for at least 3 months after ablation and depending on the individual stroke risk thereafter.2,3 With 4212 patients followed for at least 3 years for the development of heart failure, myocardial infarction, death, dementia, Alzheimer's disease, and cardiovascular hospitalization, Bunch et al.9 show that AF ablation may not only reduce stroke, but also decrease mortality risk to that of patients without AF, compared with AF patients who did not have ablation. These findings have been replicated in the large international multicentre registry.10 The latter study additionally showed that freedom from AF had an effect on stroke-free survival. If patients remained free from AF, their 7-year stroke-free survival rate was 97.8%.10,9 This translates to an annual event rate of 0.3%, representing a new ‘all-time low’ in stroke prevention in AF. How does the current study by Lin et al.11 published in this issue of the Journal enrich our knowledge on the role of catheter ablation compared with conservative medical treatment in long-term outcomes and mortality in AF patients? This study investigated long-term major adverse cardiovascular events, including total vascular events [central and peripheral TE such as stroke, transient ischaemic attack (TIA), peripheral embolism] and death in AF patients with a CHA2DS2-VASc score ≥1 who were treated with either long-term antiarrhythmic drug therapy or catheter ablation. Out of 953 patients, 174 patients undergoing radiofrequency catheter ablation were matched using propensity scores with individuals who received antiarrhythmic medication without catheter ablation, and were followed for approximately 4 years (mean follow-up 47 ± 23 months). Sinus rhythm was maintained in 39.7% patients in the medically treated group and 90.2% patients in the ablation group. The composite cardiovascular endpoint and mortality were significantly lower in patients who underwent catheter ablation. For instance, total mortality was 11.5% under medical treatment and 2.9% after AF ablation. Similarly, vascular events, namely stroke, were significantly lower in the ablated patients, i.e. 2.3 vs. 8.6%. Of note, in patients without AF recurrence mortality and stroke rates were remarkably low at 1.7 and 0.8%, respectively. The authors can be congratulated on this well-conducted, retrospective study with very encouraging results for both the physicians and patients. Their study further confirms the most important results of previously published studies on this issue, and clearly shows that catheter ablation of AF in patients with at least one risk factor for TE reduces cardiovascular mortality, which is mostly related to the reduced risk of stroke and TIA. Importantly, both AF recurrence and the CHA2DS2-VASc score predicted adverse outcomes, which underline the importance of both underlying diseases and heart rhythm. As with many retrospective studies, there are a number of unanswered questions and new challenges since the findings presented here may not be representative of other cohorts and wider populations with AF. Most importantly, the authors acknowledged the ‘underuse’ of warfarin, as only 10.5% of their medically treated patients and 2.3% of their ablated patients were on long-term warfarin. While under-use of warfarin after successful ablation may not substantially impact the TE rates,8 under-use in medically treated patients with a higher likelihood of recurrent AF and a CHA2DS2-VASc score ≥1 may be disastrous. In fact, the event rate in their medically treated cohort, i.e. cardiovascular mortality and vascular events combined, was 5.3 and 7.0% even in patients with a CHADS2 score of 0 and CHA2DS2-VASc score of 1, respectively. Consequently, the appropriate use of oral anticoagulation may shift the event rate, at least in part, to more favourable outcomes in this group. Of note, a CHADS2 score of 0 is not necessarily an equivalent of low risk as event rates in these patients can range between 0.8%/year and 3.2%/year; thus, to assume a CHADS2 score of 0 is ‘low risk’ may put patients at risk of stroke.12 Having said this, it remains to be determined what impact novel oral anticoagulants may have on any head-to-head comparison of medical vs. ablation therapy. The novel oral anticoagulants including dabigatran, rivaroxaban, and apixaban may change the landscape in TE prevention.13 Recent studies demonstrated their non-inferiority or even superiority compared with warfarin with regard to major bleeding, all-cause stroke, and mortality, but evidence of their efficacy and safety after catheter ablation is sparse. It is known that different ablation technologies, i.e. radiofrequency ablation, cryo-ablation, or circular multi-electrode duty-cycled radiofrequency ablation, result in different rates of silent cerebral ischaemia. Whether or not this may affect long-term outcomes is currently unknown. Since the authors used radiofrequency ablation, sometimes even with non-irrigated tip catheters, their results may not be extrapolated to other ablation approaches. In summary, there is a growing body of evidence that catheter ablation of AF may help reduce stroke risk and mortality. A comprehensive approach to AF management is nevertheless needed.14 More definite answers are eagerly awaited and can be expected from two prospective trials CABANA (Catheter ABlation vs ANti-arrhythmic drug therapy for Atrial fibrillation) and EAST (Early treatment of Atrial fibrillation for Stroke prevention Trial) studies that aim at establishing the appropriate roles for medical and ablative intervention for AF (www.clinicaltrials.gov). The CABANA trial is designed to test the hypothesis that catheter ablation will be superior to current rate or rhythm control therapy in reducing total mortality, whereas the recently initiated EAST study tests the hypothesis that early rhythm control therapy based on antiarrhythmic drugs and catheter ablation can prevent AF-related complications when compared with usual care. In our opinion, several previous and ongoing studies will pave the road that in the foreseeable future the answer to the patient's question ‘will catheter ablation of atrial fibrillation help me live longer and protect me against stroke?’ will be a clear ‘yes’. Conflict of interest: none declared. J.K. is supported by the German Cardiac Society St. Jude Medical Stipend.