Efficacy and safety of non-prostanoid prostacyclin receptor agonist for pulmonary hypertension: A meta-analysis

Oral non-prostanoid prostacyclin receptor agonists therapies have been recommended for pulmonary arterial hypertension in many countries. We aimed to evaluate the specific impact of non-prostanoid prostacyclin receptor agonists on pulmonary hypertension and to explore the influence of study characteristics on results. PubMed, Embase, and ClinicalTrials.gov were systematically searched from inception to July 12, 2022. Randomized controlled trials comparing non-prostanoid prostacyclin receptor agonists administration with placebo for treating pulmonary hypertension were included. Two researchers independently selected eligible studies, assessed the bias risk and extracted related data. RevMan5.1 was used for performing the statistical analysis and the assessment of bias risk of the enrolled studies. PROSPERO registered number CRD42022304172. Seven trials involving 1727 patients were included. Pooled analyses indicated non-prostanoid prostacyclin receptor agonists significantly reduced clinical worsening events (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54 to 0.74), increased 6-min walk distance (mean difference [MD], 10 m; 95% CI, 3–17 m), decreased pulmonary vascular resistance (MD, −121 dyn s/cm5; 95% CI, −172 to −69 dyn s/cm5) and increased cardiac index (MD, 0.38 L/min/m2; 95% CI, 0.26–0.50 L/min/m2) compared with the control. No significant differences in all-cause mortality (RR, 0.86; 95% CI, 0.26 to 2.78), NYHA/WHO functional class (RR, 1.16; 95% CI, 0.61 to 2.18), mean pulmonary artery pressure (MD, −0.88 mmHg; 95% CI, −2.20 to 0.44 mmHg), right atrial pressure (MD, 0.66 mmHg; 95% CI, −0.59 to 1.90 mmHg) and total adverse events (RR, 1.05; 95% CI, 0.99 to 1.10) were found between non-prostanoid prostacyclin receptor agonists group and control group. Non-prostanoid prostacyclin receptor agonists treatment exerted benefits on clinical worsening, pulmonary vascular resistance, and cardiac index in pulmonary hypertension patients, without increasing the incidence of total adverse events. •Non-prostanoid prostacyclin receptor agonists significantly reduce clinical worsening events.•Non-prostanoid prostacyclin receptor agonists significantly increase cardiac index and decrease PVR.•Non-prostanoid prostacyclin receptor agonists are safe and well-tolerated.