Contribution of pressure and flow changes to resistance reduction after pulmonary arterial hypertension treatment: a meta-analysis of 3898 patients

Abstract

BackgroundPulmonary arterial hypertension (PAH)-targeted therapies exert significant hemodynamic changes, however systematic synthesis is currently lacking.MethodsWe searched PubMed, CENTRAL, and Web of Science for studies evaluating mean pulmonary artery pressure (mPAP), cardiac index/output (CI/CO), pulmonary vascular resistance (PVR) of PAH-targeted therapies either in monotherapy or combinations as assessed by right heart catheterization in treatment-naïve PAH patients. We performed a random-effects meta-analysis with meta-regression.ResultsWe included 68 studies (90 treatment groups) with 3898 patients (age 47.4±13.2, 74% women). In studies with small PVR reduction (less than 4 WU), CI/CO increase (R2=62%) and not mPAP reduction (R2=24%) was decisive for the PVR reduction (p<0.001 and p=0.36, respectively, in the multivariable meta-regression model); however, in studies with large PVR reduction (more than 4 WU), both CI/CO increase (R2=72%) and mPAP reduction (R2=35%) contributed significantly to the PVR reduction (p<0.001 and p=0.01, respectively). PVR reduction as a percentage of the pre-treatment value was more pronounced in the oral+prostanoid i.v./s.c. combination therapy (mean difference [MD] −50.0%, 95% confidence interval [CI] −60.8%;-39.2%), compared to oral combination therapy (−41.7%, −47.6%;-35.8%), prostanoid i.v./s.c. monotherapy (−31.8%, −37.6%;-25.9%), and oral monotherapy (−21.6%, −25.4%;-17.8%). Changes in hemodynamic parameters were significantly associated with changes in functional capacity of patients with PAH as expressed by the six-minute walking distance.ConclusionCombination therapies, especially with the inclusion of parenteral prostanoids, lead to remarkable hemodynamic improvement in treatment-naïve PAH patients and may unmask the contribution of mPAP reduction to the overall PVR reduction in addition to the increase in CO.