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

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.