Bosentan effect on echocardiographic systolic pulmonary arterial pressure in systemic sclerosis-related pulmonary hypertension: a systematic review and metanalysis.

Bosentan is a dual endothelin receptor antagonist approved for the treatment of SSc digital ulcers (DU) and pulmonary arterial hypertension (PAH). Systolic pulmonary arterial pressure (sPAP) is a relevant parameter for the follow-up and prognosis of SSc-PAH. The therapeutic magnitude of bosentan in SSc-PAH is not fully understood, thus we aim to establish the degree of sPAP reduction in bosentan treated SSc-PAH patients. We performed a systematic literature review in three databases from January 2000 to June 2023, involving sPAP measurement at transthoracic echocardiography of SSc patients before and after starting bosentan. Following the study quality assessment and data extraction, we performed random-effects meta-analysis and Egger's test for publication bias. Stratified analysis was performed for mono-/combination therapy, follow up duration (≤1 year), indication for bosentan therapy (PAH or DU/mixed). In the 11 selected manuscripts, sPAP mean difference before and after bosentan therapy was - 5.63mmHg (CI95% -9.79 to -1.48, p=0.0078). In stratified analysis, sPAP mean was significantly different before and after bosentan therapy only for studies considering < 1 year of follow-up (p=0.0020), monotherapy (p=0.0140) and the strict indication for PAH (p=0.0002). Bosentan significantly decreases sPAP, a relevant prognostic marker, especially in overt SSc-PAH. However, bosentan did not decrease sPAP when started for DU/mixed indication nor for follow-up>1 year. The burden of publication bias was significant. Therefore, further studies are required to assess bosentan's haemodynamic effect in high-risk patients for SSc-PAH.