Table 2

GRADE summary of findings of PFO closure plus antiplatelet therapy vs antiplatelet therapy alone in patients with cryptogenic stroke

Outcome
(Timeframe)
Study results and measurementsAbsolute effect estimates per 1000 patient-yearsCertainty in effect estimates
(Quality of evidence)
Plain text summary
Antiplatelet therapyPFO closure plus antiplatelet therapy
Ischaemic stroke
(standardised to 5 years)
OR: 0.12
(95% CrI 0.04 to 0.27)
Direct evidence in NMA from 1257 patients in three studies
Follow-up 3.8 years
100
per 1000
13
per 1000
Moderate
Due to serious imprecision†
PFO closure plus antiplatelet therapy probably results in a large decrease in ischaemic stroke
Difference: 87 fewer
(95% CrI 100 fewer* to 33 fewer)
Death
(standardised to 5 years)
OR: 3.28
(95% CrI 0.2 to 174.22)
Direct evidence in NMA from 1257 patients in three studies
Follow-up 3.8 years
3
per 1000
9
per 1000
Moderate
Due to serious imprecision‡
There is probably little or no difference in death
Difference: 6 more
(95% CrI 3 fewer* to 9 more)
Major bleeding
(standardised to 5 years)
OR: 0.48
(95% CrI 0.2 to 1.12)
Direct evidence in NMA from 1257 patients in three studies
Follow-up 3.8 years
14
per 1000
7
per 1000
Moderate
Due to serious imprecision§
There is probably little or no difference in major bleeding
Difference: 7 fewer
(95% CrI 14 fewer* to 1 more)
Persistent¶ atrial fibrillation or flutter
(standardised to 1 year)
Relative risk: 4.84
(95% CI 1.91 to 12.26)
Based on data from 3560 patients in six studies
Follow-up 3.9 years
5
per 1000
23
per 1000
Moderate
Due to serious risk of bias††
PFO closure plus antiplatelet therapy probably increases persistent atrial fibrillation
Difference: 18 more per 1000 patients** (95% CI 5 more to 56 more)
Transient or paroxysmal atrial fibrillation or flutter
(standardised to 1 year)
Relative risk: 3.76
(95% CI 1.74 to 8.1)
Based on data from 3560 patients in six studies
Follow-up 3.9 years
5
per 1000
17
per 1000
Moderate
Due to serious risk of bias‡‡
PFO closure plus antiplatelet therapy probably increases transient atrial fibrillation
Difference: 12 more per 1000 patients**
(95% CI 3 more to 31 more)
Device or procedure-related adverse events
(standardised to 1 year)
Risk difference: 0.04
(95% CI 0.02 to 0.05)
Based on data from 3560 patients in six studies
Follow-up 3.9 years
0
per 1000
36
per 1000
High§§PFO closure plus antiplatelet therapy increase device or procedure-related adverse events
Difference: 36 more per 1000 patients**
(95% CI 23 more to 50 more)
Pulmonary embolism
(standardised to 5 years)
OR: 1.01
(95% CrI 0.09 to 11.21)
Direct evidence in NMA from 1137 patients in two studies
Follow-up 4.3 years
5
per 1000
5
per 1000
HighPFO plus antiplatelet therapy has no effect on pulmonary embolism
Difference: 0 fewer
(95% CrI 5 fewer to 48 more)
Transient ischaemic attack
(standardised to 5 years)
OR: 0.82
(95% CrI 0.32 to 2.11)
Direct evidence in NMA from 1257 patients in three studies
Follow-up 3.8 years
34
per 1000
28
per 1000
Moderate
Due to serious imprecision¶¶
There is probably little or no difference in transient ischaemic attack
Difference: 6 fewer
(95% CrI 34 fewer* to 15 more)
Systemic embolism
(standardised to 5 years)
OR: 0.83
(95% CrI 0.13 to 7.25)
Direct evidence in NMA from 1257 patients in three studies
Follow-up 3.8 years
6
per 1000
5
per 1000
HighThere is little or no difference in systemic embolism
  • The baseline risk for PFO closure was used to estimate the absolute effect in the antiplatelet arm. The baseline risk in the PFO arm was calculated based on the median risk of the outcome in the six RCTs included. This allowed for consistency in the absolute effect estimate in the PFO closure arms in tables 2 and 3, thus allowing ease in comparison.

  • *The calculated CI using risk difference, because of uncertainty in the point estimates, permits reductions greater than the point estimates in the PFO group. To avoid confusion, we have truncated to present the maximum reduction as equal to the PFO event rate.

  • †Risk of bias: not serious. Despite inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, we decided not to downgrade since we rated ischaemic stroke as an objective outcome (borderline decision). Inconsistency: not serious. Borderline decision I54%, not rated down. Imprecision: serious. Low number of events.

  • ‡Imprecision: serious. Wide CIs, included appreciable harm. Low number of events.

  • §Imprecision: serious. Low number of events.

  • ¶Defined as persistent according to the study definition or requiring a cardioversion attempt.

  • **In the first year after procedure rather than 5 years.

  • ††Risk of bias: serious. Not clearly stated how this was measured or assessed with prolonged ECG monitoring. Also, it is not clear for all events whether it was transient or persistent.

  • ‡‡Risk of bias: serious. Not clearly stated how this was measured or assessed with prolonged ECG monitoring. Also, it is not clear for all events whether it was transient or persistent.

  • §§Inconsistency: not serious. Inconsistency: one study as high 60/100 and 1 as low as 10/1000., Point estimates vary widely. Not rated down.

  • ¶¶Imprecision: serious. Wide CIs, included both appreciable benefit and harm. Low number of events.

  • NMA, network meta-analysis; PFO,  patent foramen ovale; RCT, randomised controlled trial.