Why the study?
There is no consensus on the most effective treatments of pulmonary arterial hypertension.
Do medications for pulmonary arterial hypertension reduce clinical worsening and mortality in patients with WHO group 1 PAH?
Do medications for pulmonary arterial hypertension reduce clinical worsening and mortality in patients with WHO group 1 PAH?
This network meta-analysis demonstrates that combination therapy with an ERA and PDE5i is highly effective at reducing clinical worsening in PAH, while several monotherapies probably reduce mortality.
Supports upfront ERA+PDE5i in PAH to reduce clinical worsening; extends network meta-analysis evidence favoring dual over monotherapy.
BACKGROUND: There is no consensus on the most effective treatments of pulmonary arterial hypertension (PAH). Our objective was to compare effects of medications for PAH. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception to December 2021. We performed a frequentist random-effects network meta-analysis on all included trials. We rated the certainty of the evidence using the Grades of Recommendation, Assessment, Development, and Evaluation approach. RESULTS: We included 53 randomised controlled trials with 10 670 patients. Combination therapy with endothelin receptor antagonist (ERA) plus phosphodiesterase-5 inhibitors (PDE5i) reduced clinical worsening (120.7 fewer events per 1000, 95% CI 136.8-93.4 fewer; high certainty) and was superior to either ERA or PDE5i alone, both of which reduced clinical worsening, as did riociguat monotherapy (all high certainty). PDE5i (24.9 fewer deaths per 1000, 95% CI 35.2 fewer to 2.1 more); intravenous/subcutaneous prostanoids (18.3 fewer deaths per 1000, 95% CI 28.6 fewer deaths to 0) and riociguat (29.1 fewer deaths per 1000, 95% CI 38.6 fewer to 8.7 more) probably reduce mortality as compared to placebo (all moderate certainty). Combination therapy with ERA+PDE5i (49.9 m, 95% CI 25.9-73.8 m) and riociguat (49.5 m, 95% CI 17.3-81.7 m) probably increase 6-min walk distance as compared to placebo (moderate certainty). CONCLUSION: Current PAH treatments improve clinically important outcomes, although the degree and certainty of benefit vary between treatments.
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Pitre et al. (2022) studied this question.
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