Table 1.
Contemporary Randomized Trials on Percutaneous Closure of Patent Foramen Ovale
| Trial Name | Year Published | PFO Device Used | Control Arm(s) | N | Mean Follow‐up (y) | Primary Endpoint | Results | Conclusions | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Closure | Control | P Value | ||||||||
| CLOSURE I | 2012 | STARFlex | Aspirin and/or Warfarin (INR 2–3) | 909 | 2 | Composite of stroke/TIA, all‐cause mortality, death from neurological causes | 5.5% | 6.8% |
HR 0.78 95% CI 0.45 to 1.35 P=0.37 |
Closure is not superior to medical therapy |
| PC Trial | 2013 | Amplatzer PFO Occluder | Antiplatelet therapy or oral anticoagulation | 414 | 4.1 | Composite of death, nonfatal stroke, TIA, or peripheral embolism | 3.4% | 5.2% |
HR 0.63 95% CI 0.24 to 1.72 P=0.34 |
Closure is not superior to medical therapy |
| RESPECT | 2013 | Amplatzer PFO Occluder | Aspirin or warfarin or Clopidogrel, or Aspirin with extended release dipyridamole | 980 | 2.6 | Composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization |
Intention‐to‐treat
0.66 events per 100 patients/year As‐treated 0.39 events per 100 patients/year |
Intention‐to‐treat
1.38 events per 100 patients/year As treated 1.45 events per 100 patients/year |
HR 0.49 95% CI 0.22 to 1.11 P=0.08 HR, 0.27 95% CI 0.10 to 0.75 P=0.007 |
No significant benefit for closure (intention‐to treat‐analysis) Closure is superior to medical therapy (as‐treated analysis) |
| RESPECT (Long‐term follow‐up) | 2017 | Amplatzer PFO Occluder | Aspirin or Warfarin or Clopidogrel, or Aspirin with extended release dipyridamole | 980 | 5.9a | Composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization |
Intention‐to‐treat
0.58 events per 100 patients/year New stroke of unknown mechanism 0.31 events per 100 patients/year |
Intention‐to‐treat
1.07 events per 100 patients/year New stroke of unknown mechanism 0.86 events per 100 patients/year |
HR 0.55 95% CI 0.31 to 1.0 P=0.046 HR 0.38 95% CI 0.18 to 0.79 P=0.007 |
Closure is superior to medical therapy on extended follow‐up in intention‐to‐treat analysis |
| CLOSE | 2017 | Any CE marked PFO device |
1) Antiplatelet arm: Aspirin or Clopidogrel or Aspirin with extended release dipyridamole 2) Oral anticoagulant arm: Vitamin K antagonists or NOACs |
663 | 5.3 | Recurrent fatal or nonfatal stroke |
Closure vs antiplatelet therapy:
0 |
Closure vs antiplatelet therapy
4.9% 5‐year estimate Anticoagulant vs Antiplatelet therapy 1.5% vs 3.8%, respectively, 5‐year estimate |
Closure vs antiplatelet therapy
HR 0.03 95% CI 0 to 0.26 P<0.001 Anticoagulant vs Antiplatelet therapy HR 0.43 95% CI 0.1 to 1.5 P=0.17 |
Closure is superior to antiplatelet in patients with ASA or PFO with large shunt Anticoagulant is equivalent to antiplatelet therapy |
| REDUCE | 2017 | Helex Septal Occluder and Cardioform Septal Occluder | Aspirin or Clopidogrel or Aspirin with dipyridamole | 664 | 3.2a |
1) Recurrent stroke 2) New brain infarct inclusive of silent brain infarct (SBI) |
Ischemic stroke:
1.4% New brain infarct: 5.7% |
Ischemic stroke:
5.4% New brain infarct: 11.3% |
HR 0.23 95% CI 0.09 to 0.62 P=0.002 HR 0.51 95% CI 0.29 to 0.91 P=0.04 |
Closure is superior to antiplatelet therapy |
| DEFENSE‐PFO | 2018 | Amplatzer PFO Occluder | Aspirin or Aspirin and Clopidogrel, or Aspirin and Cilostazol, or Warfarin | 120 | 2.8a | Stroke, vascular death or TIMI‐defined major bleeding |
Ischemic stroke:
0 2 year event rate: 0 New ischemic lesion on MRI: 8.8% |
Ischemic stroke:
10.5% 2 year event rate: 12.9% New ischemic lesion on MRI: 18.4% |
P=0.023 Log‐rank P=0.013 P=0.24 |
Closure in patients with high risk PFO characteristics resulted in lower rate of ischemic stroke versus medical therapy |
ASA indicates atrial septal aneurysm; CI, confidence interval; CLOSE, Closure of Patent Foramen Ovale or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence; CLOSURE I, Evaluation of the STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism through a Patent Foramen Ovale; DEFENSE‐PFO, Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High‐Risk Patent Foramen Ovale; HR, hazard ratio; INR, international normalized ratio; N, number of patients; NOACs, novel oral anticoagulants; PC, Percutaneous Closure of Patent Foramen Ovale Using the AMPLATZER PFO Occluder with Medical Treatment in Patients with Cryptogenic Embolism; PFO, patent foramen ovale; REDUCE, GORE HELEX Septal Occluder/GORE CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke or Imaging‐Confirmed TIA in Patients With Patent Foramen Ovale (PFO); RESPECT, Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment; TIA, transient ischemic attack; TIMI, thrombolysis in myocardial infarction.
Median follow‐up reported.