Rationale and Background

Atrial Fibrillation and associated stroke risk

Atrial fibrillation (AF) is the most common arrhythmia affecting about 2% of the population with at least 30 million people worldwide being diagnosed with AF. AF is associated with increased morbidity and mortality, linked to an increased risk of stroke and systemic embolism. Patients with AF have a five-fold increased risk of stroke compared to matched individuals without AF. Strokes associated with AF are more severe compared to other etiologies of stroke, with 60% of them causing major disability and 20% causing death.

Most studies assessing risk of stroke in AF have focused on clinically apparent stroke. However, with enhanced magnetic resonance imaging (MRI) techniques, the importance of silent cerebral infarction (or covert stroke) secondary to AF is now being recognized. Such changes may be existent in 50-90% of patients with AF, even amongst those thought to be at low risk of stroke. It is estimated that the incidence of silent infarction may be 2-7 times the incidence of clinically manifest strokes in patients with chronic AF. Although these infarctions are not immediately symptomatic, long-term studies suggest that such changes are related to future clinical stroke, cognitive decline, dementia, and increased mortality. Thus, silent cerebral infarction on MRI is an area of emerging importance.

Relationship between AF burden and risk of stroke

Data on the relationship between AF burden and risk of stroke is limited and not conclusive. The chair of the OCEAN steering committee (Healey) recently published the ASSERT study, showing that as little as 6 minutes of atrial arrhythmias detected within 90 days of pacemaker implant increased the risk of stroke.

It is currently unknown whether elimination or reduction in AF burden can reduce stroke risk. Evidence from the large AFFIRM trial comparing pharmacologic rhythm control to rate control suggested that attempts to reduce AF burden may actually increase risk of stroke. The increase in stroke was mediated by withdrawal of OAC in patients who were felt to have their AF “eliminated” by antiarrhythmic medication; however, the efficacy of such medication in maintaining sinus was only modest.

Increasing utilization and efficacy of catheter ablation for treatment of AF

Compared to antiarrhythmic medications, percutaneous catheter ablation is up to four times more effective in maintaining sinus rhythm. Increasingly, ablation is being utilized to treat symptomatic AF patients. The success rate, however, is not 100% but repeat procedures, typically performed within six months of the first procedure, can increase efficacy to about 80%. Giving concomitant medication can further reduce AF occurrence.

Data on the longer term efficacy of catheter ablation are more limited, but growing. Furthermore, the vast majority of post-ablation recurrences occur within the first 6-12 months post-ablation. For patients who remain arrhythmia-free for twelve months after their last procedure, the chance for late recurrence of AF is quite low (about 4% per year). Thus, a successful outcome of catheter ablation may not be accurately determined until more than 12 months has elapsed since the last ablation procedure.

The effect of successful catheter ablation of AF on risk of stroke

Given the long-term efficacy of catheter ablation, there have been several observational studies suggesting that successful AF ablation may reduce the risk of stroke. In all of these studies, OAC was stopped in a majority of patients with very low risks of stroke. Even though many of the patients included in these studies had moderate risk scores, the annual rate of stroke was still lower compared to that predicted by the scoring system.

The data from all these studies are intriguing but have not yet convinced most physicians to change their practice or influenced guidelines.

The importance of continuous, long-term monitoring for post-ablation AF

The true burden of AF can be significantly underestimated using intermittent monitoring versus long-term, continuous monitoring. More intensive monitoring has also suggested that brief, asymptomatic recurrences of AF may be more common than thought in patients who have had an apparently “successful” ablation. In the DISCERN AF study, the main finding was that post-ablation, the ratio of asymptomatic to symptomatic episodes of AF increased significantly compared to pre-ablation. Furthermore, 12% of patients had only asymptomatic episodes post-ablation. In total, catheter ablation reduced the AF burden by 86%. The implications of the brief, ongoing, asymptomatic AF episodes on the stroke risk are unknown.

Potential impact of newer options for oral anticoagulation (OAC)

Both antiplatelet therapy and OAC have been shown to reduce the risk of stroke in AF patients, but multiple studies have demonstrated the superiority of OAC with vitamin K antagonism (i.e. warfarin) over antiplatelet therapy alone in preventing stroke in higher risk AF patients. The risk is primarily determined by a patient’s concomitant risk factors (using the CHA2DS2-VASc risk score) and not by the burden of AF. Yet, despite this evidence and the possibility of ongoing asymptomatic episodes of AF post-ablation, many patients undergoing successful catheter ablation of AF wish to come off their OAC due to the difficulty in titrating warfarin dose to a therapeutic level and the need for frequent blood testing.

Recently, novel oral anticoagulants including direct thrombin inhibitors (i.e. dabigatran) and oral anti factor Xa inhibitors (i.e. rivaroxaban and apixaban) have been shown to be superior to warfarin in stroke prevention for AF with a lower accompanying risk of serious bleeding. These novel agents offer further advantage because they do not require blood monitoring or dose changes. In fact, their efficacy and ease of use has resulted in the most recent guidelines recommending these agents over warfarin for stroke prevention and also lowering the risk profile of patients who will benefit.

Current practice guidelines

Given the lack of any randomized trial data addressing the long-term risk of stroke in patients who have undergone successful AF ablation, recent Canadian and international consensus guidelines have suggested a cautious approach to discontinuing OAC. In 2010, the Canadian guidelines suggested that “in the presence of sustained normal sinus rhythm, oral anticoagulation should be discontinued only if the long-term risk of stroke is low.” In the European guidelines, there are no specific recommendations other than to state that the decision to continue long-term OAC should be based more on the risk profile of the patient as opposed to the presence or absence of AF. Also in the same (2012) guideline, there is an acknowledgement that optimal management of OAC long-term post-successful ablation remains a key “unresolved question.”