Page 13 - Journal of Structural Heart Disease Volume 2, Issue 1

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Review Article
[46]. This suggested a signi cant improvement in safety with operator experience and technical re ne- ment of the procedure.
The Prospective Randomized Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy (PREVAIL) trial was the second randomized, controlled trial conducted to further evaluate safety and e cacy with the WATCHMAN device in response to U.S. Food and Drug Admin- istration concerns over selection criteria and acute safety events [47]. The PREVAIL trial randomized patients 18 years old or older with nonvalvular AF with a CHADS2 score greater than or equal to 2 or 1 with an additional high-risk characteristic (female age ≥ 75 years, baseline ejection fraction ≥ 30 but < 35%, age 65 to 74 years and either diabetes or coro- nary disease, and age ≥ 65 years old with congestive heart failure). This was meant to include higher risk patients than were evaluated in PROTECT AF. A to- tal of 407 patients were randomized in a 2:1 fashion with 269 patients in the WATCHMAN group and 138 patients in the warfarin group. The WATCHMAN de- vice was successfully implanted in 95.1% of patients in whom implant was attempted, an improvement from PROTECT AF (p = 0.04). Furthermore, 39.1% of implants were performed by new implanters with no statistically signi cant di erence in success or in complications compared to experienced implanters demonstrating improvements in physician educa- tion and the evolution of the procedure. All 7-day complications after attempted implantation includ- ing pericardial e usion requiring surgery, pericardial e usion requiring pericardiocentesis, procedure-re- lated strokes, and device embolization occurred at signi cantly lower rate in PREVAIL compared to PROTECT AF (4.5% versus 8.7%, p = 0.004). This data was consistent with data from CAP registry demon- strating procedural complications as infrequent and signi cantly improved (Figure 4).
The PREVAIL composite 18 month e cacy endpoint (stroke, systemic embolization, and cardiovascular/un- explained death) failed to achieve the noninferiority prespeci ed criteria. Event rates in the WATCHMAN arm and the warfarin arm were similar (0.064 versus 0.063). The 18-month rate ratio of 1.07 had a 95% CrI of 0.57 to 1.89, which failed to meet the prespeci ed upper bound
12.50 10.00 7.50 5.00 2.50 0.00
PAF - 1st half
Saftey events
PAF - 2nd half
CAP PREVAIL
Figure 4. WATCHMAN safety events: PROTECT AF(PAF), Contin- ued Access Protocol Registry (CAP), Prospective Randomized Evaluation of the Watchman Left Atrial Appendage Closure De- vice in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy (PREVAIL). Safety data from PROTECT AF and CAP regis- try were compared by Reddy et al. [45]. Results of PREVAIL [47] demonstrated consistent reduction in safety events. All 7-day complications after attempted implantation including pericardi- al e usion requiring surgery, pericardial e usion requiring peri- cardiocentesis, procedure related strokes, and device emboliza- tion occurred at signi cantly lower rate in PREVAIL compared to PROTECT AF (4.5% versus 8.7%, p = 0.004).
of 1.75. The rate of stroke after 7 days after randomiza- tion was 0.0253 in the WATCHMAN arm and 0.0273 in the warfarin arm meeting prespeci ed criteria for noninferiority. Importantly, the warfarin arm ischemic stroke rate per patient years in PREVAIL (0.70) was sig- ni cantly lower than all other recent AF studies involv- ing NOACs [i.e. RE-LY (1.7) [13], ARISTOTLE (1.6) [14], and ROCKET AF (2.2) [15]].
While PROTECT AF, CAP, and PREVAIL included warfarin eligible patients, the group in most need of alternatives to anticoagulation include those nonvalvular AF patients who are unable to be treat- ed with anticoagulation. While there are no ran- domized trial data, the ASA Plavix Registry (ASAP) study evaluated such patients [48]. A total of 150 nonvalvular AF patients who were ineligible for warfarin were prospectively enrolled in this obser- vational study. Prior bleeding was the main reason for inability to be treated with warfarin. Patients were placed on with clopidogrel for 6 months after implantation of the WATCHMAN device and with aspirin indefinitely thereafter. Patients were fol- lowed up for a mean of 14.468.6 months. The ob- served event rate for stroke or systemic embolism was 2.3% per year. The expected event rate based
Sánchez, J.M. et al.
Where Do We Stand Now?
% of patients