Stroke risk for non-valvular AF is estimated with the CHA2DS2-VASc score. When patients have no risk factors, no anticoagulation is recommended with a Class III, loe B. With 1 risk factor in men and 2 in women, anticoagulation should be considered (class IIA, loe-B). When the CHA2DS2-VASc score is 2 or greater in men (3 or greater in women) anticoagulation is recommended in all with a Class I, loe-A, preferably with a NOAC (class I, loe-A). Platelet inhibitor monotherapy is prohibited with a Class III, loe-A. Patients that have or develop a long-term contra-indication for oral anticoagulation have no class I guideline accepted alternative. Instead it is recommended to modify conditions or interrupt anticoagulants (Class IIB, loe-B). Resumption of oral anticoagulants should be guided by a multidisciplinary team that weighs the risks and benefits of such a course of action (class IIA, loe-C). In patients after an intracranial haemorrhage (ICH), it is recommended to initiate or resume anticoagulation after 2-4 weeks (class IIA, loeC) choosing an agent with low intracranial bleeding risk.

There is insufficient data to support the choice of anticoagulant and no evidence at all for avoiding stroke prevention altogether, which has led to wide variations in restarting oral anticoagulation often after several months of abstinence. Over 60% does not even resume therapy after anticoagulation-associated ICH.

As the LAA is the dominant source for cardioembolic stroke, mechanical percutaneous endocardial occlusion procedures have been developed. The WATCHMAN and AMULET (both FDA- and CE approval) are the most used but others are emerging. Basically, a cardiac catheterization is performed from the Femoral Vein, passing a 14F catheter through the Inferior Caval Vein and the interatrial septum to the left atrium. The delivery system is then positioned in the LAA ostium, and the device is deployed blocking the entrance and eliminating the LAA from the circulation. The implant procedure is usually guided by trans-esophageal echo imaging to assess device size and determine optimal position before it can be released. Adequate closure is achieved in 99% of patients nowadays, with a low and manageable procedural risk of 2.5%. To avoid device-related thrombus during reendothelialization patients are treated with dual antithrombotic agents, aspirin and clopidogrel in the first 3 months, which is narrowed down to aspirin until 1 year after which time it may be discontinued.

The 5-year follow up of PROTECT-AF and PREVAIL showed that LAAO was non-inferior to vitamin K antagonist (VKA) for the primary endpoint of stroke/ TIA/systemic embolism/death (HR 0.82, p-value 0.3), while VKA-patients had significantly more major bleeding events after the implant (HR 0.48, p=0.0003). WATCHMAN LAAO is CE and FDA approved and worldwide almost 100.000 WATCHMAN implantations have now been performed. Currently no RCT outcome data are available comparing WATCHMAN LAAO to any type of NOAC. For AMULET and other LAAO devices there are no published RCT compared to either VKA or NOAC. The EWOLUTION all-comers registry data in over 1000 AF pts (73% unable to use (N)OAC, CHA2DS2-VASc 4.7) WATCHMAN LAAO showed stroke and bleeding rates 80% and 46% lower than expected compared to historical data. In 2 similar AMPLATZER-AMULET LAAO registries of \>1000 AF patients, stroke and bleeding rates were 50-60% lower. Both in the 2020 ESC and the 2019 AHA/ACC guidelines, LAAO has received a Class IIb, loe-B recommendation for stroke prevention in patients with AF that have non-reversible contra-indications for long-term anticoagulation.

The COMPARE-LAAO trial studies the effectiveness and safety of LAAO as an alternative means for stroke prevention, to establish whether outcomes in The Netherlands are comparable to literature. In the setting of a randomized controlled trial, LAA will be compared to usual care of anti-platelet therapy or nothing based on individual physician's assessment. Cost-effectiveness will be studied by comparing the additional cost of the procedure to cost of usual care, and the differences in cost between both arms for complications due to stroke and other embolism.