Summary of findings for the main comparison. Prostacyclin compared to control for pulmonary arterial hypertension.
| Prostacyclin compared to control for pulmonary arterial hypertension | ||||||
| Patient or population: pulmonary arterial hypertension Setting: outpatients Intervention: prostacyclin Comparison: control (placebo or usual care) | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of evidence (GRADE) | Comments | |
| Risk with control | Risk with prostacyclin | |||||
| Improvement in WHO functional class Mean follow‐up 16 weeks |
Study population | OR 2.39 (1.72 to 3.32) | 1066 (8 RCTs) | ⊕⊕⊕⊝ Moderate1 | ||
| 116 per 1000 | 239 per 1000 (185 to 304) | |||||
| 6MWD Mean follow‐up 15 weeks |
The mean 6MWD was 257 m* | MD 19.50 m higher (14.82 higher to 24.19 higher) | ‐ | 2283 (13 RCTs) | ⊕⊕⊝⊝ Low1,2 |
6MWD in PAH MCID is 41 m |
| Mortality Mean follow‐up 15 weeks |
Study population | OR 0.60 (0.38 to 0.94) | 2554 (15 RCTs) | ⊕⊕⊕⊝ Moderate1 | ||
| 39 per 1000 | 24 per 1000 (15 to 37) | |||||
| mPAP (the higher the mPAP, the worse the pulmonary hypertension) Mean follow‐up 11 weeks |
The mPAP ranged from 56 to 66 mmHg# | MD 3.60 mmHg lower (4.73 lower to 2.48 lower) | ‐ | 1132 (8 RCTs) | ⊕⊕⊝⊝ Low1,2 |
|
| PVR (the higher the PVR, the worse the pulmonary hypertension) Mean follow‐up 11 weeks |
The mean PVR ranged from 26 to 29 units/m2# | MD 2.81 WU lower (3.80 lower to 1.82 lower) | ‐ | 658 (7 RCTs) | ⊕⊕⊕⊝ Moderate1 | |
| Cardiac index (the lower the cardiac index, the worse the pulmonary hypertension) Mean follow‐up 11 weeks |
The mean cardiac Index ranged from 2 to 2.4 L/min/m2# | MD 0.31 L/min/m 2 higher (0.23 higher to 0.38 higher) | ‐ | 868 (6 RCTs) | ⊕⊕⊝⊝ Low1,2 |
|
| RAP (the lower the RAP, the worse the pulmonary hypertension) Mean follow‐up 11 weeks |
The mean RAP ranged from 8 to 13 mmHg# | MD 1.90 mmHg lower (2.58 lower to 1.22 lower) | ‐ | 1060 (6 RCTs) | ⊕⊕⊕⊝ Moderate1 | The higher the RAP, the worse the pulmonary hypertension |
| Dyspnoea (lower scores indicates more severe breathlessness) Mean follow‐up 17 weeks |
‐ | SMD 0.21 lower (0.32 lower to 0.11 lower) | ‐ | 1521 (8 RCTs) | ⊕⊕⊝⊝ Low1,2 |
Using an illustrative SD, this converts to a difference of 0.64 units on the Borg scale. MCID in PAH is 0.9 units |
| Quality of life Mean follow‐up 12 weeks |
‐ | SMD 0.28 better (0.04 better to 0.42 better) | ‐ | 271 (3 RCTs) | ⊕⊕⊕⊝ Moderate1 | |
| Headache+ Mean follow‐up 12 weeks |
277 per 1000 | 529 per 1000 (95% CI 501 to 593) |
3.16 (2.62 to 3.80) | 2351 (12 RCTs) |
⊕⊕⊕⊝ Moderate2 | |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). 6MWD: six‐minute walk distance; CI: confidence interval; MCID: minimum clinically important difference; MD: mean difference; OR: odds ratio; PAH: pulmonary arterial hypertension; mPAP: mean pulmonary arterial pressure; PVR: pulmonary vascular resistance; RAP: right atrial pressure; RCT: randomised controlled trials; SD: standard deviation; SMD: standardised mean difference; WHO: World Health Organization | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
1Downgraded due to the risk of bias with open‐label studies. 2Downgraded due to imprecision owing to significantly high heterogeneity, although the direction of effect is consistent. *based on only one study which published placebo data; all other studies reported a mean difference between groups. #based on baseline data; all other studies reported a mean difference between groups. +This was chosen as the most commonly experienced adverse event.