PAH-specific therapy for pulmonary hypertension and interstitial lung disease: A systemic review and meta-analysis

Abstract

ObjectivePulmonary hypertension (PH) in context with interstitial lung disease (ILD) portends serious clinical consequences and a high rate of mortality. Recently published randomized controlled trials (RCTs) which assessed the pulmonary arterial hypertension (PAH)-specific drugs for pulmonary hypertension and interstitial lung disease (PH-ILD) revealed inconsistent clinical outcomes with previous studies. We conducted a systemic review and meta-analysis to further investigate the effect of PAH-specific therapies for PH-ILD.MethodsClinical trials were searched from the EMBASE, PUBMED, and CENTRAL databases. The duration from the establishment of the database to June 2022 for RCTs evaluates the effect of PAH-specific therapy in patients with PH-ILD. RevMan 5.4 was used for the meta-analysis.ResultsA total of six articles (with a total of 791 patients) were included, including 412 patients in the treated group and 379 patients in the control group. As compared to placebo, the change of 6MWD was a significant improvement with PAH-specific therapy in the six RCTs (23.09; 95% CI, 12.07–34.12 P < 0.0001); but when the study with inhaled treprostinil was excluded, the significant improvement in the change of 6MWD from baseline was not present anymore (MD 11.01, 95%CI−6.43–28.46 P = 0.22). There was no significant improvement in the change in lung function, hemodynamic parameters, clinical worsening, all-cause death, and serious adverse effects in the treated group compared to placebo.ConclusionPAH-specific therapy significantly improved exercise capacity in the patients with PH-ILD, but this is due to the greater contribution of the study with inhaled treprostinil. Therefore, our findings still did not support the routine use of the whole PAH-specific drugs for PH-ILD.

Management of Pulmonary Hypertension Associated with Chronic Lung Disease

“…However, the inhaled administration of treprostinil or NO has been found to be a promising treatment strategy with clinical efficacy in PH-ILD. 99 Results from the INCREASE trial (a Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Subjects With Pulmonary Hypertension Due to Parenchymal Lung Disease) demonstrated that patients with ILD-PH treated with inhaled treprostinil had significant improvements in exercise, as shown by clinically relevant changes in the 6minute walking distance between the two groups. 100 In addition, a subgroup analysis of patients with IPF demonstrated that treatment with inhaled treprostinil was associated with significant improvements in forced vital capacity (FVC), although the mechanism was unclear.…”

“…However, the inhaled administration of treprostinil or NO has been found to be a promising treatment strategy with clinical efficacy in PH–ILD. 99…”

Unmasking a Silent Threat: Improving Pulmonary Hypertension Screening Methods for Interstitial Lung Disease Patients

“…Although anti-fibrotic drugs, effective for IPF and certain other progressive fibrotic ILDs, improve FVC and slow disease advancement, their impact on PH development requires additional investigation. Standard use of medications approved for treating PAH is not advised for the treatment of PH-ILD patients as their safety and effectiveness in this particular patient group remain uncertain [100]. Nevertheless, registry data suggest occasional prescriptions on an individual basis.…”