Summary of findings for the main comparison. Group 1 Pulmonary arterial hypertension ‐ PDE5i compared to placebo.
| Group 1 Pulmonary arterial hypertension ‐ PDE5i compared to placebo | ||||||
| Patient or population: people with pulmonary arterial hypertension Setting: outpatients Intervention: PDE5 inhibitors Comparison: placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with PDE5i | |||||
| Improvement in WHO functional class | 61 per 1000 | 358 per 1000 (204 to 549) | OR 8.59 (3.95 to 18.72) | 282 (4 RCTs) | ⊕⊕⊕⊕ HIGH | ‐ |
| Six‐minute walk distance | Ranges from 170 ‐ 319 ma | MD 48 metres higher (40 higher to 56 higher) | ‐ | 880 (8 RCTs) | ⊕⊕⊕⊝b MODERATE | 6MWD in PAH MCID is 41 metres |
| Mortality | 41 per 1000 | 9 per 1000 (3 to 28) | OR 0.22 (0.07 to 0.68) | 1119 (8 RCTs) | ⊕⊕⊕⊕ HIGH | ‐ |
| Quality of life SF‐36: (scores 1 to 100, higher scores indicate better QoL) EQ‐5D questionnaire: (higher scores indicate worse QoL) CHFQ: (lower scores indicate worse QoL) |
Galiè 2005a found a statistically significant improvement in all SF‐36 domains for sildenafil‐treated participants, and when compared to placebo in physical functioning (P < 0.001), general health (P < 0.001), and vitality (P < 0.05). There was also a statistically significant improvement in placebo‐treated participants in the physical functioning domain. Galiè 2005a found statistically significant improvements for the EQ‐5D current health status (P < 0.01) and utility index (P < 0.01). Sastry 2004 found a statistically significant difference for the CHFQ fatigue domain (sildenafil post‐treatment score 22.33, SD 4.82 compared to placebo post‐treatment score 20.67, SD 5.19; P = 0.04), and a non‐statistically significant difference in the emotional function domain (sildenafil post‐treatment score 37.33, SD 9.3, compared to placebo post‐treatment score 34.71, SD 10.91; P = 0.06), favouring sildenafil compared with placebo. |
163 (2 RCTs) |
‐ | Data considered too heterogeneous to meta‐analyse | ||
| PAP | ‐ | MD 6.43 mmHg lower (8.13 lower to 4.74 lower) | ‐ | 453 (6 RCTs) | ⊕⊕⊕⊝b MODERATE | The higher the mean PAP, the worse the PH |
| RAP | ‐ | MD 1.35 mmHg lower (2.34 lower to 0.36 lower) | ‐ | 341 (3 RCTs) | ⊕⊕⊕⊕ HIGH | The higher the RAP, the worse the PH |
| Cardiac index | ‐ | MD 0.28L/min/m2 higher (0.16 higher to 0.4 higher) | ‐ | 239 (4 RCTs) | ⊕⊕⊕⊝b MODERATE | The lower the cardiac index, the worse the PH |
| PVR | ‐ | MD 4.74 WU lower (6.13 lower to 3.35 lower) | ‐ | 266 (3 RCTs)) | ⊕⊕⊕⊕ HIGH | The higher the PVR. the worse the PH |
| *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; EQ‐5D: EuroQoL 5D; MCID: minimal clinically important difference; MD: mean difference; OR: odds ratio; PAP: pulmonary arterial pressure; PDE‐5i: phosphodiesterase‐5 inhibitor; PH: pulmonary hypertension; PVR: pulmonary vascular resistance; RAP: right atrial pressure; RCT: randomised controlled trials; SD: standard deviation; SF‐36: Medical Outcomes Study 36‐item short form; WU: woods units; 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 | ||||||
aPost‐treatment values for participants in the placebo group were presented in two studies only; the remaining included studies presented a mean difference only. bDowngraded due to imprecision owing to significantly high heterogeneity, although the direction of effect is consistent.