By 2030, an estimated 12.1 million people in the United States will experience atrial fibrillation (AF).1 Globally, AF is the most clinically significant arrhythmia seen in clinical practice, and its prevalence has been increasing, owing to the aging population.2 The 2019 estimated global burden of AF was 59.7 million patients, which represents a 2-fold increase in cases over the past 30 years.3 Although the use of oral anticoagulation (OAC) has increased with the development of direct oral anticoagulants (DOACs),2 a large subset of patients with AF still have absolute or relative contraindications to OAC and are at increased risk for stroke.



The risk of ischemic stroke in patients with AF is 5 times that of those without AF,1 and more than 90% of AF-related ischemic strokes originate in the left atrial appendage (LAA).5 The preferred therapy for prevention of AF stroke is OAC, but occlusion of the LAA via minimally invasive device implantation is a reasonable alternative in patients for whom long-term OAC treatment is inappropriate.6

To occlude the LAA, a delivery catheter is inserted into the femoral vein and guided to the right atrium of the heart. The atrial septum is pierced, allowing the catheter to reach the left atrium. The device is deployed at the opening of the LAA, where it opens like an umbrella and occludes the remainder of the appendage. Within approximately 45 days, a thin layer of tissue has grown around and covered the occlusion device, which remains permanently in place.7 

Who Benefits From Left Atrial Appendage Occlusion (LAAO)?

Treatment with LAAO is ideal for patients with nonvalvular AF with a CHADS2 score of 2 or greater or patients with a CHA2DS2-VASc score of 3 or greater who are not good candidates for long-term OAC.6 The CHADSscore ranges from 0 to 6 and assigns 1 point each for the presence of congestive heart failure, hypertension, age 75 years and older, and diabetes mellitus, and 2 points for the presence of stroke/transient ischemic attack. The CHA2DS2-VASc score encompasses congestive heart failure, hypertension, age 75 years and older (doubled), diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism (doubled), vascular disease, age 65 to 74 years, and female vs male sex category.6 Nonpharmacologic alternatives to OAC may be preferred for patients with a history of bleeding or risk of bleeding, advanced renal failure, high risk of falls, and a risk of drug-drug interactions, or when there are concerns about adherence to therapy.5

Not all patients benefit from LAAOs, however, and it is important for clinicians to differentiate between LAA stroke risk vs overall stroke risk when identifying patients who would benefit from LAAO. For example, a patient with risk factors for cardioembolic stroke, such as a complex aortic plaque, would still have a high risk of stroke despite undergoing LAAO; likewise, a patient who requires OAC for an indication independent of AF would still require OAC after device implantation.8 Although such patients may benefit from LAAO, risk-benefit evaluations can be complicated.9

Devices Approved by the US Food and Drug Administration

The Watchman LAA closure device (Boston Scientific Corporation) demonstrated noninferiority to warfarin for the composite outcome of stroke, systemic embolism, and cardiovascular death and was associated with a large decrease in the rate of hemorrhagic stroke.10 The Watchman was also one of several LAAO devices found to be noninferior to DOACs.11



The Watchman device is approved for patients for treatment with OAC is recommended and considered suitable,7 as initial enrollments in the pivotal trials did not include patients with OAC contraindications. The ongoing ASAP-TOO trial (ClinicalTrials.gov Identifier: NCT02928497) will assess the safety and effectiveness of the Watchman in patients for whom OAC is contraindicated.12 Most recently, the FDA approved the Watchman FLX, the frame shape of which is different from that of the original product.7

The Amplatzer Amulet LAA occluder device (Abbott) was approved by the FDA in August 2021 after demonstrating noninferiority to the Watchman device.13 Study inclusion criteria differed from those of the original Watchman device trials, and the FDA approval statement only specifies that patients must be able to tolerate short-term OAC.

Medication Management Following Implantation

Medication management following implantation can vary by patient and device. The PROTECT-AF (ClinicalTrials.gov Identifier: NCT00129545) and PREVAIL (ClinicalTrials.gov Identifier: NCT01182441) trials evaluating the Watchman device used warfarin and aspirin for 45 days, followed by clopidogrel plus aspirin for 6 months, followed by aspirin only indefinitely.8 Recently, postprocedural use of DOACs was found to be noninferior to warfarin, giving healthcare providers more freedom to choose the appropriate regimen for a particular patient.14

For patients undergoing LAAO with the Amplatzer Amulet device, medication management following the procedure is similar to that of the Watchman device. Alternatively, patients may be placed immediately on a dual antiplatelet regimen of clopidogrel and aspirin for the first 6 months and switched to monotherapy with aspirin thereafter (ClinicalTrials.gov Identifier: NCT02879448).15



Risks of left atrial appendage closure
Flip
During the Watchman clinical trials, a small percentage of people experienced stroke, clots around the device, or pericardial effusion.

LAAO Device Complications

Overall complication rates associated with LAAO therapy have declined since the approval of the Watchman device, because the implantation procedure has been modified to minimize hazards.16 That said, LAAO is not without risk. In a recently published study comparing LAAO with the Amplatzer Amulet device vs the Watchman device for stroke prophylaxis, major bleeding events and device-related thrombosis were observed in approximately 10% and 4% of patients, respectively, independent of the device used.15 Although pericardial effusion is a risk with either device, use of the Amplatzer Amulet was associated with a notably higher rate of development of pericardial effusion more than 2 days after the procedure (1.9% vs 0.4% with use of the Watchman device).13

A recent evaluation of data on more than 49,000 patients in the National Cardiovascular Data Registry LAAO Registry who underwent LAAO with the Watchman device highlighted alarming differences in procedural outcomes based on patient sex; women were twice as likely to experience major bleeding and pericardial effusion, and were more likely than men to have a longer hospital stay or die.17 The FDA released a letter to healthcare providers stating that the agency believes the benefits of LAAO continue to outweigh its risks, but that the FDA would work with device manufacturers to gain a better understanding of the issue.18 Because only the original Watchman device was evaluated,18 it is currently unknown whether the Watchman FLX and Amplatzer Amulet devices pose similar risks to women.

Despite these risks and possible complications, LAAO procedures using the Watchman, Watchman FLX, or Amplatzer Amulet device represent a safe and effective alternative to OAC for stroke prevention in patients with nonvalvular AF. Clinicians should assess individual risks of stroke and bleeding, well as other possible OAC-related concerns, to identify patients most likely to benefit from LAAO.

References

1. Atrial fibrillation. Centers for Disease Control and Prevention website. https://www.cdc.gov/heartdisease/atrial_fibrillation.htm Updated September 27, 2021. Accessed October 20, 2021.

2. Freedman B, Hindricks G, Banerjee A, et al. World Heart Federation roadmap on atrial fibrillation – a 2020 update. Global Heart. 2021;16(1):41. doi:10.5334/gh.1023

3. Kornej J, Benjamin EJ, Magnani JW. Atrial fibrillation: global burdens and global opportunities. Heart. 2021;107:516-518. doi:10.1136/heartjnl-2020-318480

4. Kornej J, Börschel CS, Benjamin EJ, Schnabel RB. Epidemiology of atrial fibrillation in the 21st century: novel methods and new insights. Circ Res. 2020;127(1):4-20. doi:10.1161/CIRCRESAHA.120.316340

5. Holmes Jr DR, Alkhouli M, Reddy V. Left atrial appendage occlusion for the unmet clinical needs of stroke prevention in non-valvular atrial fibrillation. Mayo Clin Proc. 2019;94(5):P864-874. doi:10.1016/j.mayocp.2018.09.025

6. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circ. 2019;140(2):e125-e151. doi:10.1161/CIR.0000000000000665

7. US Food and Drug Administration. WATCHMAN left atrial appendage closure device with delivery system and WATCHMAN FLX left atrial appendage closure device with delivery system – P130013/S035. Updated August 11, 2020. Accessed October 20, 2021.

8. Valderrabano M. Left atrial appendage occlusion: indications and expectations. Presented at: Southwest Valve Summit; October 5-6, 2018; Houston, Texas.

9. Boersma LV, Ince H, Kische S, et al, for the EWOLUTION investigators. Evaluating real-world clinical outcomes in atrial fibrillation patients receiving the Watchman left atrial appendage closure technology: final 2-year outcome data of the EWOLUTION trial focusing on history of stroke and hemorrhage. Circ Arrhythm Electrophysiol. 2019;12(4):e006841. doi:10.1161/CIRCEP.118.006841

10. Reddy VY, Doshi SK, Kar S, et al. 5-Year Outcomes After Left Atrial Appendage Closure: from the PREVAIL and PROTECT AF Trials. J Am Coll Cardiol. 201719;70(24):2964-2975. doi:10.1016/j.jacc.2017.10.021

11. Diener HC, Landmesser U. Percutaneous left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation. Future Neurol. Published online July 3, 2020. doi:10.2217/fnl-2020-0001

12. Assessment of the WATCHMAN device in patients unsuitable for oral anticoagulation (ASAP-TOO). ClinicalTrials.gov Identifier: NCT02928497. Updated March 26, 2021. Accessed October 20, 2021. https://clinicaltrials.gov/ct2/show/NCT02928497

13. US Food and Drug Administration. PMA P200049: FDA Summary of Safety and Effectiveness Data. Amplatzer™ Amulet™ Left Atrial Appendage Occluder.  Updated October 4, 2021. Accessed October 20, 2021.

14. Fry E, Bollempali H, Suarez K, Banchs J, Michel J. Watchman outcomes comparing post-implantation anticoagulation with warfarin versus direct oral anticoagulantsJ Interv Card Electrophysiol. 2021;61:137-144. doi:10.1007/s10840-020-00790-2

15. Lakkireddy D, Thaler D, Ellis C, et al. AmplatzerTM AmuletTM left atrial appendage occluder vs WatchmanTM device for stroke prophylaxis (AMULET IDE): a randomized controlled trial. Circ. Published online August 30, 2021. doi:10.1161/CIRCULATIONAHA.121.057063

16. Sawant AC, Seibolt L, Sridhara S, et al. Operator experience and outcomes after transcatheter left atrial appendage occlusion with the Watchman device. Cardiovasc Revascularization Med. 2020;21(4):467-472. doi:10.1016/j.carrev.2019.08.001

17. Darden D, Duong T, Du C, et al.  Sex differences in procedural outcomes among patients undergoing left atrial appendage occlusion: insights from the NDCR LAAO registry. JAMA Cardiol. Published online August 11, 2021. doi:10.1001/jamacardio.2021.3021

18. US Food and Drug Administration. Left atrial appendage occlusion (LAAO) devices potentially associated with procedural outcome differences between women and men – letter to health care providers. Updated September 27, 2021. Accessed October 20, 2021.

Posted by Haymarket’s Clinical Content Hub. The editorial staff of Cardiology Advisor had no role in this content’s preparation.

Reviewed November 2021