Who Watches the Watchmen? – LAA closure for stroke protection

By Antje Schmidt, Klinik für Neurologie, Universitätsklinikum Münster, DE

As primary source of thromboembolism in atrial fibrillation, the left atrial appendage (LAA) qualifies as a target for mechanical interventions for stroke prevention.¹ In particular for patients at high bleeding risk, local therapies, which exclude the LAA from the systemic circulation, offer a treatment alternative to oral anticoagulation for cardioembolic stroke prevention.

Over the last decades, several surgical and transcatheter approaches for LAA closure have been evaluated. Commonly applied surgical techniques to close the LAA involve epicardial or endocardial suture exclusion, stapled excision, and LAA removal by scissors or electrocautery, followed by suture closure of the LAA stump.² However, the results of observational studies on the association between surgical LAA closure and stroke protection are conflicting and there is a lack of randomized data on surgical techniques used for LAA occlusion.^2,3 Apart from surgical approaches, different transcatheter devices are employed for less invasive, percutaneous LAA occlusion. The Watchman device, for instance, which was applied in two recent randomized trials, consists of a parachute-shaped, self-expanding nitinol frame with a polyethylene cap and distal tines to secure the device in the LAA trabeculae. During the implantation procedure, an access sheath is introduced into the left atrium through transseptal puncture. The device is advanced to the tip of the access sheath, after which the sheath is withdrawn and the device deployed.⁴

The safety and efficacy of LAA closure with the Watchman device for stroke prevention has been investigated in two randomized clinical trials, PROTECT AF and PREVAIL.⁵ In PROTECT AF, 707 AF patients with a CHADS₂ score ≥ 1 were randomly assigned to either Watchman LAA closure or warfarin in a 2:1 ratio. The PREVAIL trial randomized 407 AF patients with a CHADS₂ Score ≥ 2 to Watchman LAA closure or warfarin in a 2:1 ratio. In both trials, all patients received warfarin with an INR target of 2-3 for 6 weeks after the procedure to allow endothelialization of the device. Thereafter, patients who received the Watchman device were transitioned to dual antiplatelet therapy with aspirin and clopidogrel for 6 months, followed by aspirin monotherapy.

In PROTECT AF, LAA closure was superior to warfarin for the primary endpoint of stroke, systemic embolism or cardiovascular mortality at 3.8 years of follow-up.⁵ However, a high rate of procedural complications prompted the initiation of the second randomized trial, PREVAIL. The aim of the smaller PREVAIL trial was to confirm procedural safety, particularly among operators without prior Watchman experience.

The 5-year outcomes of PREVAIL, alone and as part of a meta-analysis with PROTECT AF, were recently published in the Journal of the American College of Cardiology.⁵ In the PREVAIL trial alone, the first composite coprimary endpoint of stroke, systemic embolism, or cardiovascular/unexplained death did not achieve statistical noninferiority compared to warfarin, whereas the second coprimary endpoint of post-procedure ischemic stroke or systemic embolism achieved noninferiority.⁵ In the meta-analysis of both trials, the composite endpoint was comparable between LAA closure and warfarin. However, differences in the prevalence of hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding clearly favored LAA closure (HR: 0.20; p = 0.0022; HR: 0.45; p = 0.03; HR: 0.59; p = 0.027; HR: 0.73; p = 0.035; HR: 0.48; p = 0.0003).⁵

A definite limitation of both trials is that all patients received warfarin with an INR target of 2-3 for 6 weeks after the procedure to allow endothelialization of the device. Therefore, the results of PROTECT AF and PREVAIL cannot be directly transferred to AF patients with contraindications to oral anticoagulation. Beyond that, LAA closure has not yet been tested against direct oral anticoagulants associated with less bleeding complications than warfarin.^6,7 Nonetheless, we should certainly watch out for transcatheter LAA closure, which might become a valuable treatment alternative for cardioembolic stroke prevention in future.

References

1. Caixeta A, Silva EO de A, Généreux P. Percutaneous left atrial appendage occlusion: putting the most lethal human attachment behind bars. Arq. Bras. Cardiol. 2012;99:968–970.
2. Chatterjee S, Alexander JC, Pearson PJ, Feldman T. Left atrial appendage occlusion: lessons learned from surgical and transcatheter experiences. Ann. Thorac. Surg. 2011;92:2283–2292.
3. Dawson AG, Asopa S, Dunning J. Should patients undergoing cardiac surgery with atrial fibrillation have left atrial appendage exclusion? Interact Cardiovasc Thorac Surg. 2010;10:306–311.
4. Price MJ. Left atrial appendage occlusion with the WATCHMAN™ for stroke prevention in atrial fibrillation. Rev Cardiovasc Med. 2014;15:142–151.
5. Reddy VY, Doshi SK, Kar S, Gibson DN, Price MJ, Huber K, Horton RP, Buchbinder M, Neuzil P, Gordon NT, Holmes DR, PREVAIL and PROTECT AF Investigators. 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials. J. Am. Coll. Cardiol. 2017;70:2964–2975.
6. Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FWA, Zhu J, Wallentin L, ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 2011;365:981–992.
7. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM, ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 2013;369:2093–2104.