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Antiplatelets

PC Trial: Percutaneous Closure of PFO with Amplatzer Occluder vs Medical Therapy in Cryptogenic Embolism (Meier et al., 2013)

In patients younger than 60 with PFO and prior ischemic stroke, TIA, or peripheral thromboembolic event of presumed paradoxical embolic origin, does percutaneous closure with the Amplatzer PFO Occluder reduce death / nonfatal stroke / TIA / peripheral embolism compared with medical therapy alone? Companion publication to the original RESPECT in the same NEJM 2013 issue.

Meier B et al. (NEJM 2013;368:1083-1091) · doi:10.1056/NEJMoa1211716 · 414 patients

Population

Included

  • Age younger than 60 years
  • Prior ischemic stroke, transient ischemic attack, or peripheral thromboembolic event presumed to be of paradoxical embolic origin through a PFO
  • TEE-confirmed PFO with right-to-left shunt
  • No other identifiable source of embolism after standard workup

Excluded

  • Identifiable alternative source of embolism
  • Age 60 or older
  • Indication for ongoing anticoagulation independent of the index event
  • Contraindication to either PFO closure or to antiplatelet/anticoagulant therapy

Primary Outcome

Composite of death, nonfatal stroke, TIA, or peripheral embolism at mean ~4-year follow-up

PFO Closure (Amplatzer)
3 / 100
Medical Therapy
5 / 100

Negligible absolute difference

Primary composite at ~4 years

Risk ratio HR 0.6395% CI 0.24–1.62p = 0.34

Safety

New-onset atrial fibrillation

PFO Closure (Amplatzer)

2.9%

Medical Therapy

1%

New-onset atrial fibrillation occurred more frequently in the closure arm (numerically 2.9% vs 1.0%), but the difference was not statistically significant in this small trial. Periprocedural complications were generally modest with the Amplatzer device. Source: Meier B et al., NEJM 2013;368:1083-1091.

Trial Design

Type

  • Multicenter, randomized, open-label, controlled superiority trial with blinded endpoint adjudication
  • 1:1 randomization (Amplatzer PFO Occluder : medical therapy)
  • 29 sites in Europe, Canada, Brazil, and Australia
  • Investigator-initiated; sponsor support from St. Jude Medical
  • Underpowered due to lower-than-expected event rate (only 18 primary events accrued)

Timeline

Enrolled February 2000 to February 2009; mean follow-up 4.1 years (closure) and 4.0 years (medical); published NEJM 2013

N

414

Enrollment

414 patients (204 closure / 210 medical therapy) at 29 sites in Europe, Canada, Brazil, and Australia. Enrolled February 2000 to February 2009. Mean follow-up 4.1 years (closure) / 4.0 years (medical). Amplatzer PFO Occluder (St. Jude Medical). Underpowered — only 18 primary events accrued. Published NEJM 2013.

ClinicalTrials.gov

NCT00166257

Bedside Pearl

PC trial (NEJM 2013) was the second major PFO closure RCT; Amplatzer device, N=414, age <60, NEGATIVE primary (3.4% vs 5.2%, HR 0.63, P=0.34). Underpowered (only 18 events). Secondary nonfatal stroke and TIA both numerically favored closure but missed significance. Together with CLOSURE-I (2012) and original RESPECT (2013, same issue), framed the pre-2017 ambiguity. Historical context only.

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