TY - JOUR T1 - Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00313-2022 SP - 00313-2022 AU - Ioannis T. Farmakis AU - Elena Vrana AU - Sophia-Anastasia Mouratoglou AU - Stefanos Zafeiropoulos AU - Stavros Zanos AU - George Giannakoulas Y1 - 2022/01/01 UR - http://openres.ersjournals.com/content/early/2022/06/30/23120541.00313-2022.abstract N2 - Background Although the initial use of combination treatment has been proved beneficial for patients’ clinical outcome, there is scarce data on its hemodynamic effects.Objective To evaluate the effect of an initial combination of PAH-targeted therapies on hemodynamic parameters in treatment-naïve PAH patients.Methods A systematic search of PubMed, CENTRAL and Web of Science was performed. We considered eligible studies with an intervention of initial PAH-targeted combination therapy in treatment-naïve PAH patients with or without monotherapy control. A random effects meta-analysis was performed for the difference between baseline and follow-up in pulmonary vascular resistance (PVR) and other hemodynamic parameters.Results Of 880 patients receiving initial combination therapy PVR was reduced by −6.5 WU (95%CI −7.4; −5.7) or by −52% (95%CI −56%; −48%, I2=0%) compared to baseline. Initial triple therapy including a parenteral prostanoid resulted in significantly greater PVR reduction (−67% versus −50% with all other combination therapies, p=0.01). The effect was more pronounced in younger patients (p=0.02). Compared to baseline, there was −12.2 mmHg (95%CI −14.0; −10.4) decrease in mean pulmonary artery pressure, 0.9 l min·m−2 (95%CI 0.8; 1.1) increase in cardiac index, −3.2 mmHg (95%CI, −4.1; −2.3) decrease in right atrial pressure and 8.6% (95%CI 6.9; 10.3) increase in mixed venous oxygen saturation. In the controlled studies, initial combination therapy reduced PVR by −4.2 WU (95%CI −6.1; −2.4) compared to monotherapy.Conclusion Initial combination therapy leads to remarkable hemodynamic amelioration. Parenteral prostanoids should be considered early, especially in more severely affected patients, to enable RV reverse remodeling.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Ioannis T. Farmakis has nothing to disclose.Conflict of interest: Elena Vrana has nothing to disclose.Conflict of interest: Sophia-Anastasia Mouratoglou has nothing to disclose.Conflict of interest: Stefanos Zafeiropoulos has nothing to disclose.Conflict of interest: Stavros Zanos has nothing to disclose.Conflict of interest: George Giannakoulas has received fees for lectures and/or consultations from Actelion, Bayer, ELPEN Pharmaceuticals, GlaxoSmithKline, Janssen, MSD, Pfizer, Lilly, and United Therapeutics. ER -