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Neurology Clinical Trial Database

PINNACLE FLX

Protection Against Embolism for Non-valvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology

Year of Publication: 2023

Authors: Shephal K. Doshi, Saibal Kar, Ashish Sadhu, ..., the PINNACLE FLX investigators

Journal: Journal of the American Heart Association

Citation: J Am Heart Assoc. 2023;12:e026295. DOI: 10.1161/JAHA.122.026295


Clinical Question

What are the 2-year safety and efficacy outcomes of the next-generation WATCHMAN FLX left atrial appendage closure device in patients with nonvalvular atrial fibrillation?

Bottom Line

The WATCHMAN FLX device demonstrated favorable safety and efficacy through 2 years, meeting the prespecified secondary endpoint of ischemic stroke or systemic embolism at 3.4% with superior anatomic closure rates compared to the first-generation device.

Major Points

  • Single-arm prospective trial of 400 enrolled patients across 29 US centers evaluating next-generation WATCHMAN FLX device
  • Successfully implanted in 395 patients (98.8%) with 100% effective LAA closure at 1 year
  • 2-year ischemic stroke/systemic embolism rate of 3.4% met performance goal of <8.7%
  • No device embolizations, pericardial effusions, or device-related thrombi after 1 year
  • 90% of patients had no detectable peridevice leak at 1 year, all residual leaks ≤3mm

Design

Study Type: Single-arm, prospective, nonrandomized trial

Randomization:

Blinding: None - single-arm study

Follow-up Duration: 2 years

Centers: 29

Countries: United States

Sample Size: 400

Analysis: Kaplan-Meier estimates for clinical outcomes, exact binomial methodology and Monte Carlo simulations for sample size calculation using SAS version 9.4


Inclusion Criteria

  • Nonvalvular atrial fibrillation
  • CHA2DS2-VASc score ≥2 for men or ≥3 for women
  • Able to take prescribed postimplant antithrombotic medication regimen
  • Appropriate rationale for nonpharmacologic approach to stroke prevention
  • No other diagnoses requiring long-term anticoagulation

Exclusion Criteria

  • Valvular atrial fibrillation
  • CHA2DS2-VASc score <2 for men or <3 for women
  • Unable to take prescribed postimplant antithrombotic medication
  • Diagnoses requiring long-term anticoagulation

Arms

FieldWATCHMAN FLX
InterventionWATCHMAN FLX left atrial appendage closure device implantation followed by protocol-specified anticoagulation regimen (DOAC plus aspirin through 45 days, then dual antiplatelet therapy through 6 months, then aspirin indefinitely)
DurationSingle procedure with 2-year follow-up

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Primary safety endpoint: occurrence of death, ischemic stroke, systemic embolism, or device/procedure-related events requiring open cardiac surgery or major endovascular intervention within 7 days/discharge; Primary effectiveness endpoint: effective LAA closure (peridevice flow ≤5mm) at 12 monthsPrimarySafety: 0.5% (2/400); Effectiveness: 100% (342/342)Safety: P<0.0001; Effectiveness: P<0.0001
2-year ischemic stroke or systemic embolismSecondary3.4% (annualized rate 1.7%)Met performance goal of <8.7%
All-cause mortality at 2 yearsSecondary9.3%
Cardiovascular death at 2 yearsSecondary5.5%
All stroke at 2 yearsSecondary3.4%
Major bleeding (BARC 3 or 5)Adverse10.1% at 2 years
Pericardial effusion requiring interventionAdverse1.0%
Device embolizationAdverse0%

Subgroup Analysis

More than 70% of all major bleeding events occurred within 6 months of procedure when patients were on oral anticoagulation or dual-antiplatelet therapy per protocol


Criticisms

  • Single-arm study design compared to performance goal rather than randomized control
  • Patients required to take oral anticoagulation until LAA seal demonstration, limiting generalizability to patients with absolute contraindications to anticoagulation
  • 4% delta for secondary efficacy endpoint contains element of arbitrariness
  • Sample size may not be large enough to provide robust estimates of rare clinical events
  • Observational design limits ability to definitively establish causal relationships

Funding

Boston Scientific Corporation

Based on: PINNACLE FLX (Journal of the American Heart Association, 2023)

Authors: Shephal K. Doshi, Saibal Kar, Ashish Sadhu, ..., the PINNACLE FLX investigators

Citation: J Am Heart Assoc. 2023;12:e026295. DOI: 10.1161/JAHA.122.026295

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