We conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacological interventions for pulmonary arterial hypertension (PAH).
MEDLINE, Cochrane register, EMBASE, CINAHL and clinicaltrials.gov were searched (January 1, 1990 - March 3, 2016). Randomized controlled trials (RCTs) of approved pharmacological agents - endothelin receptor antagonists (ERA), phosphodiesterase inhibitors (PDE5i), oral/inhaled and intravenous/subcutaneous prostanoids, riociguat, and selexipag, alone or in combination for pulmonary arterial hypertension (PAH) reporting at least one efficacy outcome were selected.
31 RCTs with 6,565 patients were selected. In network meta-analysis, compared to a median placebo rate of 14.5%, clinical worsening was estimated at 2.8% with riociguat (risk ratio [RR] 0.19, 95% CI 0.05,0.76), 3.9% with ERA+PDE5i (RR 0.27, 95% CI 0.14,0.52) and 5.7% with PDE5i (RR 0.39, 95% CI 0.24,0.62). For improvement in functional status, compared to 16.2% in the placebo group, improvement in at least 1 NYHA/WHO functional class was estimated at 81.8% with intravenous/subcutaneous prostanoids (RR 5.06, 95% CI 2.32,11.04), 28.3% with ERA+PDE5i (RR 1.75, 95% CI 1.05,2.92) and 25.2% with ERA (RR 1.56, 95% CI 1.22,2.00). Differences in mortality were not significant. Adverse events leading to discontinuation of therapy were highest with oral/inhaled prostanoids (RR 2.92, 95% CI 1.68,5.06) and selexipag (RR 2.06, 95% CI 1.04,3.88) compared to placebo.
Currently approved pharmacological agents have varying effects on morbidity and functional status in patients with PAH. Future comparative effectiveness trials are warranted with a focus on patient-centered approach to therapy.