Issues
Patient Selection
Currently, it is unclear which patient groups would benefit the most from LAA occlusion as there are no clinical trials looking at this issue. Current evidence and expert opinion would suggest that LAA occlusion offers the greatest benefit in patients with AF who have a high-stroke risk but who are also at a high risk of bleeding or have suffered a major bleed and are therefore intolerant of oral anticoagulants. Unfortunately, the current clinical trial data do not sufficiently address the use of LAA occlusion in patients not treated with oral anticoagulants. Approximately 50% of patients with AF who are at risk for stroke are not treated with oral anticoagulation; device therapy in this patient population would be an important therapeutic alternative. Currently, the only data available in this high-risk population subset come from the European Percutaneous Left Atrial Appendage Transcatheter Occlusion (PLAATO) study and the Aspirin Plavix Feasibility Study with Watchman Left Atrial Appendage Closure Technology (ASAP) registry. In the ASAP registry, the predicted stroke rate based on CHADS2 score was 7.3% per year while the actual stroke rate following LAA closure was 2.3% per year. Table 3 shows the conditions in which LAA occlusion may be considered in patients intolerant of oral anticoagulants. A recent European expert consensus statement proposed a patient algorithm for stroke prevention in AF; this is summarised in figure 2.
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Figure 2.
Algorithm for stroke prevention in patients with atrial fibrillation. Recommendations of the European Heart Rhythm Society and the European Association of Percutaneous Cardiovascular Interventions 2014. Reproduced by permission from Meier et al.26 HAS-BLED, Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly; LAA, left atrial appendage; OAC, oral anticoagulants.
Device/Procedural Safety
Device and procedural safety has always been of utmost importance among physicians involved with this technology. The early studies (PLAATO, PROTECT AF) revealed a substantial incidence of periprocedural safety events that included cardiac perforation requiring surgical repair, pericardial effusion with tamponade requiring pericardiocentesis, device embolisation, procedure-related stroke and vascular complications. Fortunately, the incidence of these complications has markedly decreased with increasing experience among operators, device iterations and improved training techniques. In the PROTECT AF trial, the first half of the study revealed a procedure-related safety event of 9.9% that dropped by 50% to 4.8% in the second half of the study. The reduction in these events was also seen in the Continued Access Protect AF (CAP) registry where the rate of procedure-related safety events was 4.1%. The recently published PREVAIL trial was designed to assess the safety and efficacy of the WATCHMAN LAA device. There were significant reductions in safety events in this trial compared with the PROTECT AF trial; early safety events were seen in 2.2% of device patients compared with 4.8% in the same group in PROTECT AF, and overall adverse events were lower in PREVAIL compared with PROTECT AF, 4.2% vs 8.7%; p=0.004. Importantly the rates of pericardial effusions needing surgical repair decreased from 1.6% to 0.4%, p=0.027, and those requiring pericardiocentesis decreased from 2.9% to 1.5%. It should be noted that mortality is worse in patients with pericardial effusion/tamponade treated surgically versus those treated with pericardiocentesis. Table 4 details the comparison of outcomes in device patients in PROTECT AF, CAP and PREVAIL trials. Eventually, the early safety hazard of device closure procedures, which is currently in the range of 2.2–4.2%, must be balanced against the long-term bleeding risk associated with oral anticoagulants. For example, the annual bleeding risk for warfarin has been estimated at 0.6% for fatal bleeds, 3% for major bleeds and 9.6% for all bleeds. There is a 2–5 time increase in the incidence of intracranial haemorrhage with the use of warfarin, which translates to 3500 intracranial bleeds annually.
Incomplete closure of LAA following epicardial or endocardial device closure has also been investigated. As previously mentioned, surgical data indicate that there is a higher incidence of stroke following incomplete surgical exclusion of LAA. A recent analysis of the PROTECT AF trial found that incomplete LAA occlusion defined as any flow around the device was found in 40.9% of patients at the 45-day TEE examination and decreased over time to 33.8% at 6 months and 32.1% at 12 months, p=0.001. The clinical impact of peri-device flow was negligible as the authors found no interaction between peri-device flow and outcomes and the use of continued anticoagulation did not decrease the risk of thromboembolic events
Cost Effectiveness
There are very few studies that have looked at the cost effectiveness of LAA device occlusion versus oral anticoagulants. A recent study examined the lifetime costs, quality-adjusted life-years and incremental cost-effectiveness ratio of LAA occlusion with the WATCHMAN device in relation to dabigatran and warfarin in patients with AF. This analysis was performed in the context of the Ontario health services in Canada. Warfarin therapy was found to have the lowest discounted quality-adjusted life-years at 4.55, followed by dabigatran at 4.64 and LAA occlusion at 4.68 (Table 5). Compared with warfarin, the incremental cost-effectiveness ratio for LAA occlusion was $41 565 and dabigatran was extendedly dominated given that dabigatran was more expensive per additional unit of cost effectiveness. They concluded that LAA occlusion is cost effective compared with warfarin. A similar analysis by Bryan Yan et al looked at LAA occlusion with the WATCHMAN device compared with aspirin, aspirin and clopidogrel, warfarin and dabigatran 150 mg or 110 mg. They concluded that LAA occlusion was cost effective with an incremental cost-effectiveness ratio of $975 per quality-adjusted life-years gained.
There are issues with the current cost-effectiveness data; estimates of effectiveness are obtained from a single randomised trial with restrictive enrolment and limited follow-up, thus these are not based on actual real-world clinical use data; second, there would be regional and geographical variability in cost effectiveness that would be reflective of insurance and medical costs in these localities; third, multiple assumptions were made in the development of this cost-effectiveness analyses due to limited data on the new strategies; and finally, it is unclear what would happen in the real world once the device is formally approved for clinical use.
Other benefits of LAA exclusion
The LARIAT device has been shown to lead to electrical isolation of LAA, leading to acute reduction in the LAA voltage with inhibition of the capture of LA during LAA pacing. Similarly, a recent analysis also suggested that there might be a decrease in arrhythmia burden with ligation of LAA.