Haemodynamic effects of PAH-targeted therapies in pulmonary hypertension due to lung disease: A systematic review and meta-analysis

Ioannis T Farmakis; Polychronis Vazakidis; Ioannis Doundoulakis; Alexandra Arvanitaki; Stefanos Zafeiropoulos; Afroditi Boutou; Haralambos Karvounis; George Giannakoulas

doi:10.1016/j.pupt.2021.102036

Haemodynamic effects of PAH-targeted therapies in pulmonary hypertension due to lung disease: A systematic review and meta-analysis

Pulm Pharmacol Ther. 2021 Jun:68:102036. doi: 10.1016/j.pupt.2021.102036. Epub 2021 May 9.

Authors

Ioannis T Farmakis¹, Polychronis Vazakidis², Ioannis Doundoulakis², Alexandra Arvanitaki³, Stefanos Zafeiropoulos⁴, Afroditi Boutou⁵, Haralambos Karvounis¹, George Giannakoulas⁶

Affiliations

¹ Department of Cardiology, AHEPA University Hospital, Thessaloniki, Greece.
² Department of Cardiology, 424 General Military Training Hospital, Thessaloniki, Greece.
³ Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College, London, United Kingdom.
⁴ Elmezzi Graduate School of Molecular Medicine and Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA.
⁵ Department of Respiratory Medicine, G. Papanikolaou Hospital, Thessaloniki, Greece.
⁶ Department of Cardiology, AHEPA University Hospital, Thessaloniki, Greece. Electronic address: ggiannakoulas@auth.gr.

PMID: 33979684
DOI: 10.1016/j.pupt.2021.102036

Abstract

Background: Pulmonary hypertension (PH) is a negative predictor in patients with lung disease and/or hypoxia (group 3 PH). Current guidelines do not endorse the use of targeted therapies for pulmonary arterial hypertension (PAH) in patients with group 3 PH, due to lack of strong evidence. However, a variety of studies have examined the effect of PAH-targeted therapies in group 3 PH with mixed methods and conflicting results.

Objective: To evaluate the effect of PAH-targeted therapies on haemodynamic parameters as assessed by right heart catheterization in patients with group 3 PH.

Methods: Search strategy included PubMed and CENTRAL databases for randomized controlled trials from inception until Jan 30, 2020. We hand searched review articles, clinical trial registries and reference lists of retrieved articles. The primary outcome was the effect of PAH-targeted therapies on haemodynamic parameters [mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI) and right atrial pressure (RAP)] in patients with group 3 PH, while secondary outcomes were 6-min walking distance (6MWD), brain natriuretic peptide (BNP) and quality of life (QoL).

Results: Five studies with a total of 140 patients were included. PAH-targeted therapies improved significantly mPAP [mean difference (MD) -4.02 mmHg, 95% CI -7.95;-0.09], and PVR [standardized mean difference (SMD) -0.29, 95% CI -0.50;-0.07], but not CI (SMD 0.23, 95% CI -0.23; 0.70) or RAP (MD 0.26 mmHg, 95% CI -18.75; 19.27). PAH-targeted therapies significantly increased the 6MWD by 38.5 m (95% CI 17.6; 59.4), while they did not manage to improve QoL (SMD -3.42, 95% CI -14.74; 7.91) or BNP values. There was no effect of oxygenation by the PAH-targeted therapies compared to placebo.

Conclusion: PAH-targeted therapies slightly improved mPAP and PVR in group 3 PH, without affecting CI. Larger RCTs targeted in specific subpopulations are needed to extract more robust conclusions.

Protocol registration: Open Science Framework 10.17605/OSF.IO/56FDW.

Keywords: Chronic lung disease; Group 3 pulmonary hypertension; Haemodynamic; Meta-analysis; Targeted medical therapy.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Familial Primary Pulmonary Hypertension
Hemodynamics
Humans
Hypertension, Pulmonary* / drug therapy
Hypertension, Pulmonary* / etiology
Pulmonary Arterial Hypertension*
Quality of Life