Fast track — ArticlesPercutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial
Introduction
Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting an estimated 6 million individuals in the USA.1 Since atrial fibrillation mainly affects elderly people, its prevalence is expected to increase in parallel with the increasing age of the population, with a predicted 15·9 million cases by 2050.1, 2, 3, 4, 5 The lifetime risk for development of atrial fibrillation is one in four in men and women 40 years of age and older.6 Stroke, the most serious complication of atrial fibrillation, occurs in 5% of non-anticoagulated patients every year. The risk of stroke increases substantially with age, from 1·5% in individuals aged 50–59 years to 23·5% for those aged 80–89 years.6, 7, 8, 9 Stroke is the third most frequent cause of death in the USA and the leading cause of serious disability. Therefore, stroke prophylaxis is a crucial component of management of atrial fibrillation.
Although membrane-active antiarrhythmic drugs10, 11, 12, 13 and catheter ablation provide symptomatic relief for patients with atrial fibrillation, neither method is sufficiently reliable in preventing thromboembolic events, and long-term oral anticoagulation therapy is recommended irrespective of the rhythm management strategy. Randomised controlled trials have shown that warfarin is effective in preventing stroke, more so than aspirin and combination aspirin-clopidogrel.14, 15, 16, 17, 18, 19, 20, 21 Despite its proven efficacy, warfarin is often not well tolerated by patients, has a very narrow therapeutic range, and has a high risk for bleeding complications.22 Furthermore, the effectiveness of anticoagulation varies because of interactions with some foods and other medications; even with frequent monitoring and dose adjustments, patients' test results are outside of the therapeutic range in up to half of all blood drawings.23 Partly for these reasons, only around 50% of patients who are eligible for long-term warfarin are treated with it.24
Pharmacological alternatives to warfarin have been investigated,25, 26, 27, 28 and several new anticoagulants seem promising;29 even if they prove to be safe, however, they will not address many of the problems related to bleeding or compliance or the need for lifelong treatment. On the basis of echocardiography and autopsy studies showing that the left atrial appendage (LAA) was the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation,30, 31, 32 percutaneous catheter-based devices have been developed to close and thereby effectively exclude the LAA from the systemic circulation. Pilot studies have shown acceptable risk-to-benefit ratios for these non-pharmacological alternatives to chronic warfarin therapy.33, 34, 35, 36, 37, 38
The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) study36 examined the efficacy and safety of percutaneous closure of the LAA in patients with non-valvular atrial fibrillation. The study was designed to assess the non-inferiority of the device against chronic warfarin therapy.
Section snippets
Patients
This prospective, randomised controlled trial was undertaken at 59 sites in the USA and Europe. Enrolment began in February, 2005, and ended in June, 2008. Patients aged 18 years or older with paroxysmal, persistent, or permanent non-valvular atrial fibrillation were eligible for enrolment if they had a CHADS2 risk score of 1 or more (ie, at least one of the following: previous stroke or transient ischaemic attack, congestive heart failure, diabetes mellitus, hypertension, or were 75 years or
Results
Figure 1 shows the trial profile. Patients were followed for an aggregate of 1065 patient-years. Mean follow-up per patient was 18 months (SD 10). Table 1 shows the baseline characteristics and risk factors of the study participants.
The device was successfully implanted in 88% (408/463) of patients assigned to this intervention and in 91% (408/449) of those in whom implantation was attempted (figure 1). At the 45-day follow-up, 349 (86%) of 408 patients with an implanted device met TEE criteria
Discussion
In view of the prevalence of atrial fibrillation and the difficulties associated with chronic treatment with warfarin—such as complications related to bleeding and the need for continuous monitoring of INR—new approaches for stroke prevention in cases of atrial fibrillation have been pursued. The strategy of LAA obliteration evolved from the finding that in patients with non-valvular atrial fibrillation, the LAA is the most common site of thrombi.30, 31, 32, 45 This randomised controlled trial
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