Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis

Network diagram for risk of clinical worsening in randomised controlled trials of pulmonary arterial hypertension treatments. Each node represents a drug or drug combination that has been tested in trials; the size of the nodes is proportional to the number of patients that have received that drug or drug combination; and the thickness of the connecting lines is proportional to the number of trials. PDE5i: phosphodiesterase-5 inhibitor; ERA: endothelin receptor antagonist; inh: inhalation; i.v.: intravenous; s.c.: subcutaneous; PRA: prostacyclin receptor agonist.

Forest plot for dichotomous outcomes. The vertical line indicates any effect. Figure 4 presents data in absolute effects with minimally important difference thresholds and Grades of Recommendation, Assessment, Development, and Evaluation ratings. ERA: endothelin receptor antagonist; PDE5i: phosphodiesterase-5 inhibitor; PRA: prostacyclin receptor agonist; inh: inhalation; i.v.: intravenous.

Network estimates of the effects of pulmonary arterial hypertension medications versus placebo on clinical and haemodynamic outcomes, presented in absolute risk difference per 1000 patients (95% CI); negative values indicate fewer events and positive values indicate more events per 1000. Colour arrangement reflects certainty of evidence. All estimates are network estimates unless otherwise specified. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) working group grades of evidence are as follows. Interpretation: each node estimate is compared against placebo; the comparative effectiveness of a treatment on an outcome versus another treatment can be assessed by comparing respective cells; 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). 6MWD: 6-min walk distance; SAE: serious adverse events; ERA: endothelin receptor antagonist; PDE5i: phosphodiesterase-5 inhibitor; PRA: prostacyclin receptor agonist; inh: inhalation; i.v.: intravenous; s.c.: subcutaneous; MID: minimally important difference. GRADE rating: ^#: imprecision; ^¶: inconsistency; ⁺: rate down three times for imprecision; ^§: rate down twice for imprecision; ^ƒ: risk of bias.