Catheter-based left atrial appendage closure is a new method for preventing thromboembolism in cases of atrial fibrillation. In a randomised trial with 707 patients, closure with the Watchman plug (Boston Scientific, St. Paul, MN) was non-inferior to warfarin therapy after 18 months (16), and produced significantly better results than warfarin therapy after an average follow-up of 3.8 years (17).
A composite endpoint comprising stroke, systemic embolism and cardiovascular mortality was used to evaluate treatment efficacy. Only patients who tolerated warfarin were included in the study; in the group that underwent catheter-based left atrial appendage closure, warfarin therapy was mandatory for 45 days after implantation.
Owing to a procedure-related complication rate of 8.7 % in the first seven days following the procedure (4.0 % pericardial effusion requiring drainage, 1.1 % ischaemic stroke, 0.4 % embolisation of the cardiac plug and 3.2 % vascular complications) (18), the US Food and Drug Administration (FDA) ruled that further evidence would be required before the product could be approved.
This formed the basis for a new study, in which 407 patients with atrial fibrillation were randomised to catheter-based left atrial appendage closure or to anticoagulant therapy with warfarin alone (18). At least 25 % of the procedures were required to be performed at institutions without previous experience with the method. In this study, left atrial appendage closure did not prove as efficacious as anticoagulant therapy with respect to the composite endpoint of stroke, systemic embolism and cardiovascular mortality after 18 months of follow-up. The incidence of procedure-related complications was reduced to 4.5 %.
A similar incidence of complications (4.2 %) was reported in a registry of 566 patients who had undergone catheter-based left atrial appendage closure (18). In 2015, on the basis of the available evidence, the FDA approved closure with the Watchman plug as an alternative to anticoagulant therapy. The procedure has been shown to be cost-effective compared to pharmaceutical treatment alone (19).
In our dataset, clinical events occurred in six out of 27 patients. The most serious complication (death due to stroke) occurred in the patient in whom closure could not be successfully performed. Of the 26 patients who underwent catheter-based left atrial appendage closure, two experienced procedure-related complications, which is in line with the numbers in the Watchman studies (16, 18) and a registry study with Amplatzer cardiac plugs (6.5 %) (20). One patient has had life-threatening complications, which we believe to be the result of late atrial appendage perforation. This is a rare complication following catheter-based closure that has been described previously (21). What constitutes an acceptable incidence of complications must be judged in relation to the anticipated efficacy in terms of stroke prevention.
Our dataset is small, and in the absence of a control group it is difficult to draw conclusions about treatment efficacy. The median CHA2DS2-VASc score in our dataset is 4, which corresponds to an expected incidence of stroke/TIA of approximately 4 % per year (22). During our one-year follow-up, four patients experienced stroke or TIA, a number that might appear on the high side.
One of the cases of TIA was probably attributable to embolisation as a result of carotid artery stenosis, against which catheter-based left atrial appendage closure of course offers no protection. It is therefore important to investigate other causes of stroke also in patients with atrial fibrillation. In one of the patients with TIA, brain MRI revealed a lacunar infarct, which is usually attributable to small vessel disease and not cardiac embolism.
It is worth noting that none of the patients experienced intracranial or gastrointestinal haemorrhage during the period from discharge to one-year follow-up. The median HAS-BLED score was 2, which corresponds to an estimated risk of severe bleeding of 1.9 % per year (22). A low incidence of bleeding after catheter-based left atrial appendage closure is consistent with findings in other studies (16, 20).
In the United States, catheter-based left atrial appendage closure is approved as an alternative to anticoagulant therapy. In Europe, most catheter-based closures are performed in patients in whom anticoagulant therapy is considered contraindicated. This is a paradox, since the randomised trials of the closure procedure included patients who tolerated warfarin (16, 18). The efficacy of anticoagulant therapy in preventing stroke in patients with atrial fibrillation is very well documented (8), and in the absence of contraindications, anticoagulant therapy is the clear first-line treatment.
Intracranial haemorrhage during ongoing anticoagulant therapy has been the indication for catheter-based left atrial appendage closure in the majority of patients at Oslo University Hospital. Those with a history of intracerebral haemorrhage usually do not receive thromboembolism prophylaxis.
Acetylsalicylic acid has been used as an alternative to anticoagulant therapy, but offers poor protection against thromboembolism in cases of atrial fibrillation (22 % stroke reduction with acetylsalicylic acid versus 64 % with warfarin) (8). The absolute reduction in haemorrhage risk with acetylsalicylic acid is modest compared to the bleeding risk with anticoagulant therapy (8). European guidelines on atrial fibrillation include only a weak recommendation for catheter-based left atrial appendage closure in patients for whom anticoagulant therapy is contraindicated or who are at high risk of bleeding (3).
Various approaches are adopted with respect to blood-thinning after left atrial appendage closure. There remains a risk of thrombosis until the cardiac plug undergoes endothelialisation after 3–6 months. In the randomised trials with the Watchman plug, the standard protocol specified anticoagulant therapy for the first 45 days after closure, followed by dual antiplatelet therapy with acetylsalicylic acid and clopidogrel for six months, and acetylsalicylic acid monotherapy thereafter (16, 17).
Dual antiplatelet therapy for six months after catheter-based left atrial appendage closure, followed by acetylsalicylic acid monotherapy, has been shown to be an equally valid alternative (23) and most institutions recommend such a regime (15).
However, good results have also been obtained with acetylsalicylic acid monotherapy following the procedure (24), and dual antiplatelet therapy entails an increased risk of bleeding compared to acetylsalicylic acid monotherapy (25). On this basis, we at Oslo University Hospital now recommend acetylsalicylic acid monotherapy.
If the 45-day follow-up reveals satisfactory closure and the absence of thrombus formation on the cardiac plug, then discontinuation of acetylsalicylic acid after six months is recommended if there is no other indication for use. If another indication is present, then acetylsalicylic acid should be continued indefinitely. The reason that many patients in our dataset nevertheless received dual antiplatelet therapy was that they had undergone percutaneous coronary intervention or percutaneous aortic valve replacement close to catheter-based left atrial appendage closure.
Patients with atrial fibrillation who require these procedures and who have an indication for anticoagulant therapy represent a major challenge for the clinician. Anticoagulant therapy offers poor protection against stent thrombosis, dual antiplatelet therapy offers poor protection against thromboembolism, and the combination of anticoagulant and antiplatelet therapy results in a high risk of bleeding (26). Catheter-based left atrial appendage closure in combination with antiplatelet therapy has therefore been proposed for such patients (15).
Several cardiac plugs have been approved for use in Europe (27). Only the Watchman plug has been used in randomised trials (16, 17), and this is the only cardiac plug approved in the United States. In spite of this, Amplatzer cardiac plugs are the most frequently used in Europe, and we have also opted for these at Oslo University Hospital. Registry data from more than 1 000 patients have shown that use of Amplatzer cardiac plugs results in fewer cases of stroke and bleeding than would be expected from CHA2DS2-VASc and HAS-BLED scores, and the incidence of procedure-related complications is at the same level as for the Watchman plug (20). Nevertheless, we acknowledge that the lack of randomised trials of Amplatzer cardiac plugs is a weakness.
More evidence is required in general before extensive use of catheter-based left atrial appendage closure can be recommended. We believe this treatment should initially be reserved for patients at high risk of stroke and with a contraindication for anticoagulant therapy, as assessed on a case-by-case basis.
To date, no randomised studies have compared percutaneous catheter-based left atrial appendage closure with NOAC therapy, with antiplatelet therapy alone, or with no treatment. In a forthcoming Scandinavian study, 750 patients with atrial fibrillation and intracerebral haemorrhage within the last six months will be randomised to either catheter-based left atrial appendage closure with an Amplatzer cardiac plug or pharmaceutical treatment. The results of this study are awaited with great interest (28). We hope that Norwegian neurologists will actively recruit patients to the study.