Stroke Prevention in Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial increases in the risk for stroke and systemic thromboembolism. With the successful introduction of the first non-vitamin K antagonistdirect oral anticoagulant agent (NOAC) in 2009, the role of vitamin K antagonists has been replaced in most clinical settings except in a few conditions for which NOACs are contraindicated. Data for the use of NOACs in different clinical scenarios have been accumulating in the past decade, and a more sophisticated strategy for patients with AF is now warranted. JACC: Asia recently appointed a working group to summarize the most updated information regarding stroke prevention in AF. The aim of this statement is to provide possible treatment options in daily practice. Local availability, cost, and patient comorbidities should also be considered. Final decisions may still need to be individualized and based on clinicians’ discretion. This is part 2 of the statement.

. Meta-analyses also indicated that NOACs were superior to warfarin in preventing thromboembolic events and lowering the risk for bleeding in individuals with AF and mild to moderate CKD. 18,19 In several large observational studies based on Asian populations, all 4 NOACs also showed comparable or lower risk for thromboembolism and a lower risk for bleeding than warfarin in patients with mild to moderate CKD. 20,21 PATIENTS WITH SEVERE CKD (CrCl 15-29 mL/min).
Major NOAC trials, except the ARISTOTLE trial,   warfarin did not reduce mortality, ischemic events, or stroke and instead increased the risk for significant bleeding. 25     In the past few years, no specially designed clinical trial has been conducted to compare the risk for gastrointestinal bleeding among these four NOACs.
Analysis from real-world evidence may provide some clues (    Values are HR (95% CI), P value unless otherwise indicated. Bold denotes statistical significance. a Defined as serum alanine transaminase or aspartate transaminase >2 times the upper limit of normal or total bilirubin 1.5 times the upper limit of normal. b Defined as patients with cirrhosis who presented with any complications, including ascites, hepatic encephalopathy, spontaneous bacteria peritonitis, or esophageal varicose bleeding. c Defined as subjects with liver cirrhosis, viral hepatitis, or abnormal alanine transaminase or aspartate transaminase >2 times the upper limit of normal.       Perioperative bridging for surgical procedures is generally not required for patients taking NOACs.
NOACs can be omitted for 1 day before a lowbleeding risk procedure and 2 days before a highbleeding risk procedure.
In patients with AF who have CrCl <50 mL/min, dabigatran should be omitted for 2 days before a low-bleeding risk procedure and 4 days before a high-bleeding risk procedure.
NOAC regimens can be resumed on the first day after a low-bleeding risk procedure and on the second day after a high-bleeding risk procedure. NOACs are as effective and safe as VKAs in planned cardioversion. In combination with transesophageal echocardiography, NOACs are useful in early cardioversion.

REVERSAL AGENTS
NOACs caused less intracranial and less lifethreatening bleeding than VKAs in phase 3 trials, [8][9][10][11] especially in Asians. 42 Moreover, patients experiencing major bleeding on NOACs had favorable outcomes compared with those on warfarin. As more patients have now been put on NOACs, the number of patients who experience bleeding episodes is increasing. Figure 3   Active Dabigatran) trial. 66 Andexanet alfa is a recombinant modified human factor Xa decoy protein that is catalytically inactive, but it can bind factor Xa inhibitors with high affinity. 67   The interruption and resumption strategy for DOACs is based on the pharmacokinetic properties of NOACs, procedure-associated bleeding risk, and creatinine clearance (CrCl) levels. Refer to Table 8 to determine levels of periprocedural bleeding risk. CrCl ¼ creatinine clearance; NOAC ¼ non-vitamin K antagonist oral anticoagulant. different subspecialties is needed, and nonpharmacologic therapy could be provided.

NONPHARMACOLOGIC MANAGEMENT
The LAA is thought to be the predominant site of thrombus formation in patients with nonvalvular AF.
A large transesophageal echocardiographic study of 1,420 patients with valvular AF or atrial flutter showed that extra-LAA thrombosis is very rare. 69  showed that the Amulet or Watchman device was noninferior to NOACs for major AF-related events in patients with nonvalvular AF. 72 However, the total patient number was only 402, and the study was underpowered to prove its effect on stroke prevention. 72 The Amulet IDE (AMPLATZERÔ AmuletÔ LAA Occluder Trial) showed that the Amulet occluder was noninferior to the Watchman device for the overall safety and effectiveness but superior in the rate of LAA occlusion among patients with nonvalvular AF at increased risk for stroke. 73 The LAmbre device had favorable clinical outcomes for stroke prevention in patients with nonvalvular AF in a prospective, multicenter, observational study in China. 74 Procedure-related complications and device-related complications need more attention. 75 The antithrombotic strategy after LAA occlusion has not been evaluated in large-scale randomized trials, particularly in patients with absolute contraindications to long-term oral anticoagulant therapy. For patients with nonvalvular AF with contraindications to oral anticoagulant agents, either an epicardial catheter approach (eg, Lariat system) or mini-invasive thoracoscopic LAA occlusion or exclusion may be a better alternative. 76,77 Percutaneous LAA occlusion may be considered for patients who have absolute  There is recent interest in applying LAA occlusion in patients with ESRD. 78 But the current data on safety and efficacy are limited to 5 small studies with a total of 84 patients. 78 It is too early to recommend LAA occlusion as an effective alternative therapy for patients with ESRD.

SURGICAL OCCLUSION OR EXCISION OF THE LAA.
The large randomized controlled LAAO III trial provided the evidence that LAA occlusion during cardiac surgery reduced long-term stroke risk in patients with AF, most of whom continued the ongoing antithrombotic therapy after surgery. 79 Observational studies from Asia found that thoracoscopic LAA occlusion or excision had a reasonably low risk for  thromboembolism without oral anticoagulation after the procedure. 76

MOBILE TECHNOLOGY
Mobile technology has been used more widely in the screening and diagnosis of AF. 86