Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy - PREVAIL

May 15, 2018
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Presenter/Author:
Vivek Yerrapu Reddy, MD
Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Atritech/Boston Scientific
Date Presented:
11/02/2017
Date Published:
05/11/2018
Date Updated:
05/15/2018
Original Posted Date:
06/30/2014
References

Contribution To Literature:

The PREVAIL trial failed to demonstrate that left atrial appendage occlusion was noninferior to warfarin at preventing cardiovascular/unexplained death, stroke, or systemic embolism at 18 months.

Description:

The goal of the trial was to evaluate percutaneous left atrial appendage (LAA) closure compared with long-term warfarin among patients with atrial fibrillation (AF). The PREVAIL trial was designed to provide confirmatory findings from the PROTECT-AF trial regarding the safety and efficacy of percutaneous LAA closure.


Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Patients with AF with a CHADS2 score ≥2 (or CHADS2 score = 1 with an additional risk factor and not eligible for aspirin)

    Number of screened applicants: 461
    Number of enrollees: 407
    Mean patient age: 74%
    Percentage female: 32%

Exclusions:

  • Indication for clopidogrel or use of clopidogrel 7 days prior to enrollment
  • Requirement for long-term anticoagulation other than AF
  • Contraindication to warfarin or aspirin
  • Stroke/TIA in the last 90 days
  • Symptomatic carotid stenosis
  • Patent foramen ovale or atrial septal defect requiring treatment

Primary Endpoints:

  • Death, ischemic stroke, systemic embolism, or procedure/device-related complication requiring major intervention (cardiovascular or endovascular) at 7 days
  • Cardiovascular/unexplained death, stroke, or systemic embolism at 18 months
  • Stroke or systemic embolism from 7 days to 18 months

Secondary Endpoints:

  • Cardiac perforation, pericardial effusion with tamponade, ischemic stroke, device embolization, or other vascular complications

Drug/Procedures Used:

Patients with nonvalvular AF and CHADS2 score ≥2 were randomized to percutaneous LAA closure with the WATCHMAN device and discontinuation of warfarin (n = 269) versus long-term warfarin therapy (n = 138).

Principal Findings:

Overall, 407 patients were randomized. The mean age was 74 years, 32% were women, mean CHADS2 score was 2.6, 34% had diabetes, and 28% had prior stroke/transient ischemic attack (TIA). Implant success was achieved in 95% (implant success was achieved in 93% of new operators).

The early safety outcome of death, ischemic stroke, systemic embolism, or procedure/device-related complication requiring major intervention at 7 days occurred in 2.2% of the device group. The upper one-sided confidence interval (2.62%) was lower than the prespecified criterion for success (2.67%), thus satisfying the prespecified performance goal.

The first co-primary efficacy outcome of cardiovascular/unexplained death, stroke, or systemic embolism at 18 months occurred in 0.064 of the device group compared with 0.063 of the warfarin group. The upper one-sided confidence interval (1.89) was higher than the prespecified criterion for success (1.75).

The second co-primary efficacy outcome of stroke or systemic embolism from 7 days to 18 months occurred in 0.0253 of the device group compared with 0.0200 of the warfarin group. The upper one-sided confidence interval (0.027) was lower than the prespecified criterion for success (0.028), thus achieving noninferiority.

Cardiac perforation, pericardial effusion with tamponade, ischemic stroke, device embolization, or other vascular complications occurred in 4.4% of the device group. Cardiac perforation requiring surgical repair occurred in 0.4%, and pericardial effusion with tamponade requiring pericardiocentesis or window occurred in 1.5%.

Pooled meta-analysis of PREVAIL and PROTECT-AF trials at 5 years: Cardiovascular death, stroke, or systemic embolism occurred in 2.8% of the device group versus 3.4% of the warfarin group (p = 0.27). Major bleeding or nonprocedure-related bleeding occurred in 1.7% of the device group versus 3.6% of the warfarin group (p = 0.0003).

Pooled analysis of PROTECT-AF, PREVAIL, CAP, and CAP2 trials: Device-related thrombus was present in 3.74%. Stroke or systemic embolism occurred in 7.46 per 100 patient-years among those with device-related thrombus versus 1.78 per 100 patient-years among those without device-related thrombus (p < 0.001). Predictors of device-related thrombus included history of TIA/stroke, permanent atrial fibrillation, vascular disease, left atrial dilatation, and left ventricular systolic dysfunction.

Interpretation:

Among patients with AF, percutaneous closure of the LAA is feasible. Compared with the earlier PROTECT-AF trial, there was improved procedural implant success with reduced device-related complications. Percutaneous closure of the LAA was noninferior to warfarin at preventing stroke or systemic embolism from 7 days to 18 months; however, noninferiority was unable to be established in regards to cardiovascular/unexplained death, stroke, or systemic embolism at 18 months. Failure to achieve noninferiority with this particular outcome may have partly been due to a lower than expected event rate in the control arm. In a pooled analysis of four trials, device-related thrombus was detected in 3.74% and was a predictor of stroke or systemic embolism.

In select patients with nonvalvular AF, LAA closure is an alternative to warfarin therapy for stroke prevention. However, the role of LAA closure needs to be considered in the context of novel oral anticoagulants, which provide enhanced stroke prevention and reduction in hemorrhagic stroke.

References:

Dukkipati SR, Kar S, Holmes DR, et al. Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes. Circulation 2018;May 11:[Epub ahead of print].

Reddy VK, Doshi SK, Kar S, et al., on behalf of the PREVAIL and PROTECT-AF Investigators. Left Atrial Appendage Closure: 5-Year Outcomes of the PREVAIL and PROTECT-AF Trials. J Am Coll Cardiol 2017;70:2964-75.

Editorial Comment: Saw J. Long-Term Results With Left Atrial Appendage Closure: Watching the Watchman. J Am Coll Cardiol 2017;70:2976-8.

Presented by Dr. Vivek Y. Reddy at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2017), Denver, CO, November 2, 2017.

Holmes DR Jr, Kar S, Price MJ, et al. Prospective Randomized Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients with Atrial Fibrillation Versus Long-Term Warfarin Therapy: The PREVAIL Trial. J Am Coll Cardiol 2014;64:1-12.

Dr. David Holmes, released March 9, 2013.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Pericardial Disease

Keywords: Stroke, Ischemic Attack, Transient, Warfarin, Risk Factors, Pericardiocentesis, Atrial Appendage, Embolism, Diabetes Mellitus, Pericardial Effusion, TCT17, Transcatheter Cardiovascular Therapeutics


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