An in-depth evaluation of the efficacy and safety of various treatment modalities for chronic thromboembolic pulmonary hypertension: A systematic review and network meta-analysis

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a major risk for pulmonary hypertension with poor prognosis. Limited data is available on the optimal treatment of choice. We aimed to comprehensively assess the efficacy and safety of CTEPH targeted therapies and update the evidence.

Methods: We searched PubMed, Scopus, and the Cochrane library up to December 2023 to include randomized controlled trials comparing different therapies in patients with CTEPH. Primary outcomes were 6-minute walk distance (6 MWD), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (mPAP). While secondary outcomes were the mean right atrial pressure (mRAP), Borg dyspnea score, cardiac output (CO), cardiac index, adverse events, and all-cause mortality.

Results: Fourteen RCTs comprising 1047 patients were included in this network meta-analysis. Regarding 6 MWD, PADN (MD=113.59, 95% CI: 53.80; 173.39), BPA (MD=48.84, 95% CI: 27.99; 69.69), riociguat (MD=42.59, 95% CI: 22.01; 63.18), treprostinil (MD=41.60, 95% CI: 17.07; 66.13), and macitentan (MD=34.00, 95% CI: 3.50; 64.50) were favored compared to placebo. In terms of PVR, BPA (MD=-392.19, 95% CI: -571.77; -212.62), treprostinil (MD=-287.20, 95% CI: -475.63; -98.77), PADN (MD=-280.61, 95% CI: -506.69; -54.52), bosentan (MD=-176.00, 95% CI: -340.91; -11.09), and riociguat (MD=-171.61, 95% CI: -298.40; -44.81) displayed statistically significant results.

Conclusion: Current therapeutic modalities are effective in terms of improving exercise capacity, pulmonary hemodynamics, and reducing adverse events and all-cause mortality. Overall, BPA and PADN were superior to all other targeted medications in the studied outcomes.

Keywords: BPA; CTEPH; Chronic thromboembolic pulmonary hypertension; Meta-analysis; PADN.

Fig. 1

PRISMA flow diagram showing the two-phase screening process.

Fig. 2

Forest plot for each primary outcome assessing the efficacy. A) 6-minute walk distance; B) Pulmonary vascular resistance; C) Mean pulmonary artery pressure.

Fig. 3

Forest plot for each secondary outcome assessing the efficacy. A) Mean right atrial pressure; B) Borg dyspnea score; C) Cardiac index; D) Cardiac output.

Fig. 4

Forest plot for each secondary outcome assessing the safety. A) Any adverse events; B) All-cause mortality.

Fig. 5

Risk of bias graph and risk of bias summary.

Fig. 6

Network diagram for the primary outcomes assessing the efficacy in RCTs of CTEPH treatments. Each node represents an intervention that has been tested in trials; the size of the nodes is proportional to the number of patients that have received the intervention; and the thickness of the connecting lines is proportional to the number of trials. A) 6-minute walk distance; B) Pulmonary vascular resistance; C) Mean pulmonary artery pressure.

Fig. 7

Network diagram for the secondary outcomes assessing the efficacy in RCTs of CTEPH treatments. Each node represents an intervention that has been tested in trials; the size of the nodes is proportional to the number of patients that have received the intervention; and the thickness of the connecting lines is proportional to the number of trials. A) Mean right atrial pressure; B) Borg dyspnea score; C) Cardiac index; D) Cardiac output.

Fig. 8

Network diagram for the secondary outcomes assessing the safety in RCTs of CTEPH treatments. Each node represents an intervention that has been tested in trials; the size of the nodes is proportional to the number of patients that have received the intervention; and the thickness of the connecting lines is proportional to the number of trials. A) Adverse events; B) All-cause mortality.