Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis

Background Although the initial use of combination treatment has been proven to be beneficial for patients’ clinical outcomes, there are scarce data on its haemodynamic effects. The objective of the present study was to evaluate the effect of an initial combination of pulmonary arterial hypertension...

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Main Authors: Ioannis T. Farmakis, Elena Vrana, Sophia-Anastasia Mouratoglou, Stefanos Zafeiropoulos, Stavros Zanos, George Giannakoulas
Format: Article
Language:English
Published: European Respiratory Society 2022-10-01
Series:ERJ Open Research
Online Access:http://openres.ersjournals.com/content/8/4/00313-2022.full
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author Ioannis T. Farmakis
Elena Vrana
Sophia-Anastasia Mouratoglou
Stefanos Zafeiropoulos
Stavros Zanos
George Giannakoulas
author_facet Ioannis T. Farmakis
Elena Vrana
Sophia-Anastasia Mouratoglou
Stefanos Zafeiropoulos
Stavros Zanos
George Giannakoulas
author_sort Ioannis T. Farmakis
collection DOAJ
description Background Although the initial use of combination treatment has been proven to be beneficial for patients’ clinical outcomes, there are scarce data on its haemodynamic effects. The objective of the present study was to evaluate the effect of an initial combination of pulmonary arterial hypertension (PAH)-targeted therapies on haemodynamic parameters in treatment-naïve PAH patients. Methods A systematic search of PubMed, Cochrane Central Register of Controlled Trials 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 haemodynamic parameters. Results In 880 patients receiving initial combination therapy PVR was reduced by −6.5 Wood Units (95% CI −7.4–−5.7 Wood Units) 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 mmHg) decrease in mean pulmonary artery pressure, 0.9 L·min−1·m−2 (95% CI 0.8–1.1 L·min−1·m−2) increase in cardiac index, −3.2 mmHg (95% CI −4.1–−2.3 mmHg) 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 Wood Units (95% CI −6.1–−2.4 Wood Units) compared to monotherapy. Conclusion Initial combination therapy leads to remarkable haemodynamic amelioration. Parenteral prostanoids should be considered early, especially in more severely affected patients, to enable right ventricular reverse remodelling.
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spelling doaj.art-4894943af6e3454db8b48c9e133c1c092023-06-07T13:30:36ZengEuropean Respiratory SocietyERJ Open Research2312-05412022-10-018410.1183/23120541.00313-202200313-2022Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysisIoannis T. Farmakis0Elena Vrana1Sophia-Anastasia Mouratoglou2Stefanos Zafeiropoulos3Stavros Zanos4George Giannakoulas5 Dept of Cardiology, AHEPA University Hospital, Thessaloniki, Greece Dept of Cardiology, AHEPA University Hospital, Thessaloniki, Greece Dept of Anesthesiology and Intensive Care, Aristotle University of Thessaloniki, AHEPA University Hospital of Thessaloniki, Thessaloniki, Greece Elmezzi Graduate School of Molecular Medicine and Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA Elmezzi Graduate School of Molecular Medicine and Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA Dept of Cardiology, AHEPA University Hospital, Thessaloniki, Greece Background Although the initial use of combination treatment has been proven to be beneficial for patients’ clinical outcomes, there are scarce data on its haemodynamic effects. The objective of the present study was to evaluate the effect of an initial combination of pulmonary arterial hypertension (PAH)-targeted therapies on haemodynamic parameters in treatment-naïve PAH patients. Methods A systematic search of PubMed, Cochrane Central Register of Controlled Trials 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 haemodynamic parameters. Results In 880 patients receiving initial combination therapy PVR was reduced by −6.5 Wood Units (95% CI −7.4–−5.7 Wood Units) 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 mmHg) decrease in mean pulmonary artery pressure, 0.9 L·min−1·m−2 (95% CI 0.8–1.1 L·min−1·m−2) increase in cardiac index, −3.2 mmHg (95% CI −4.1–−2.3 mmHg) 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 Wood Units (95% CI −6.1–−2.4 Wood Units) compared to monotherapy. Conclusion Initial combination therapy leads to remarkable haemodynamic amelioration. Parenteral prostanoids should be considered early, especially in more severely affected patients, to enable right ventricular reverse remodelling.http://openres.ersjournals.com/content/8/4/00313-2022.full
spellingShingle Ioannis T. Farmakis
Elena Vrana
Sophia-Anastasia Mouratoglou
Stefanos Zafeiropoulos
Stavros Zanos
George Giannakoulas
Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis
ERJ Open Research
title Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis
title_full Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis
title_fullStr Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis
title_full_unstemmed Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis
title_short Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis
title_sort haemodynamic effects of initial combination therapy in pulmonary arterial hypertension a systematic review and meta analysis
url http://openres.ersjournals.com/content/8/4/00313-2022.full
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