Table 3.
GRADE assessment of quality of evidence
| Quality assessment |
Summary of findings |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| Number of participants (studies) |
Risk of bias | Inconsistency | Indirectness | Imprecision | Publication bias | Relative effect or risk difference (95% CI) | Anticipated absolute effects Time frame: 5 years |
Quality of evidence | |
| Risk with medical therapy | Risk difference with PFO closure (95% CI) |
||||||||
| Non-fatal ischaemic stroke (critical outcome) | |||||||||
| 1968 (3 RCTs) |
Serious limitations* | No serious limitations | No serious limitations |
Imprecise CI includes benefit and no effect |
Undetected |
RR 0.61 (0.34 to 1.07) |
52/1000† |
20 fewer per 1000 (from 34 fewer to 4 more) |
⊕⊕ОО LOW due to risk of bias and imprecision |
| TIA (important outcome) | |||||||||
| 1968 (3 RCTs) |
Serious limitations* | No serious limitations | No serious limitations | No serious limitations‡ | Undetected |
RR 0.76 (0.44 to 1.32) |
27/1000§ |
6 fewer per 1000 (from 15 fewer to 9 more) |
⊕⊕⊕О MODERATE due to risk of bias |
| Total mortality (critical outcome)¶ | |||||||||
| 1968 (3 RCTs) | Serious limitations* | No serious limitations | No serious limitations |
Imprecise CI includes benefit and harm |
Undetected |
RD 0.00 (−0.01, 0.01) |
15/1000** |
0 fewer per 1000 (from 10 fewer to 10 more) |
⊕⊕ОО LOW due to risk of bias and imprecision |
| Major bleeding (important outcome) | |||||||||
| 2254 (3 RCTs) |
Serious limitations* | No serious inconsistency | No serious limitations‡ | No serious limitations | Undetected |
RD 0.00 (−0.01, 0.02) |
7/1000†† |
0 more per 1000 (10 fewer to 20 more) |
⊕⊕⊕О MODERATE due to risk of bias |
| Atrial fibrillation (important outcome)‡‡ | |||||||||
| 2254 (3 RCTs) |
Serious limitations* | Serious inconsistency§§ | No serious limitations |
Imprecise CI includes benefit and harm |
Undetected |
RD 0.02 (−0.02, 0.06) |
12/1000¶¶ |
20 more per 1000 (20 fewer to 60 more) |
⊕ООО VERY LOW due to risk of bias, inconsistency and imprecision |
*Serious risk of bias due to substantial loss to follow-up in each of the three studies; loss to follow-up greater in medical therapy arms. See text for other potential sources of bias in individual studies.
†Baseline rate derived from pooled RESPECT and PC Trial data—21 non-fatal ischaemic strokes detected in medical therapy arm over a total of 2019 patient-years×1000×5 years.
‡Although CI includes benefit and harm, magnitude of extremes for this type of outcome deemed too low to appreciably impact patient decision-making.
§Baseline rate derived from pooled RESPECT and PC Trial data—11 TIAs detected in medical therapy arm over a total of 2019 patient-years×1000×5 years.
¶None of deaths due to stroke, treatment related bleeding, or device implantation.
**Baseline rate derived from pooled RESPECT and PC Trial data—6 cases of total mortality detected in medical therapy arm over a total of 2019 patient years×1000×5 years.
††Baseline rate derived from pooled RESPECT and PC Trial data—3 cases of major bleeding detected in medical therapy arm over a total of 2019 patient-years×1000×5 years.
‡‡Type of atrial fibrillation (transient vs sustained) not reported in medical therapy arms or in PFO closure arm of RESPECT study. Of 31 cases of atrial fibrillation in the remaining 2 studies 19 were characterised as transient.
§§I2=93%, p≤0.00001.
¶¶Baseline rate derived from pooled RESPECT and PC Trial data—five cases of atrial fibrillation detected in the medical therapy arm over a total of 2019 patient-years×1000×5 years.
PFO, patent foramen ovale; RD, risk difference; RR, risk ratio; RCT, randomised controlled trial; TIA, transient ischaemic attack.