Abstract
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.
Footnotes
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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.
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- Received February 6, 2022.
- Accepted July 5, 2022.
- Copyright ©The authors 2022
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