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

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

doi:10.1016/j.pupt.2021.102036

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…Although a previous study has shown that PAH-specific therapies slightly improved mPAP and PVR in group 3 PH, our results were inconsistent because only two RCTs were included for pooled analysis ( 24 ). Few previous studies demonstrated a positive effect on FVC in treatment with PAH-specific therapy for PH-ILD and our finding was consistent with it ( 18 ).…”

Section: Discussionmentioning

confidence: 71%

PAH-specific therapy for pulmonary hypertension and interstitial lung disease: A systemic review and meta-analysis

Zhao

Zhang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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ObjectivePulmonary hypertension (PH) in context with interstitial lung disease (ILD) portends serious clinical consequences and a high rate of mortality. Recently published randomized controlled trials (RCTs) which assessed the pulmonary arterial hypertension (PAH)-specific drugs for pulmonary hypertension and interstitial lung disease (PH-ILD) revealed inconsistent clinical outcomes with previous studies. We conducted a systemic review and meta-analysis to further investigate the effect of PAH-specific therapies for PH-ILD.MethodsClinical trials were searched from the EMBASE, PUBMED, and CENTRAL databases. The duration from the establishment of the database to June 2022 for RCTs evaluates the effect of PAH-specific therapy in patients with PH-ILD. RevMan 5.4 was used for the meta-analysis.ResultsA total of six articles (with a total of 791 patients) were included, including 412 patients in the treated group and 379 patients in the control group. As compared to placebo, the change of 6MWD was a significant improvement with PAH-specific therapy in the six RCTs (23.09; 95% CI, 12.07–34.12 P < 0.0001); but when the study with inhaled treprostinil was excluded, the significant improvement in the change of 6MWD from baseline was not present anymore (MD 11.01, 95%CI−6.43–28.46 P = 0.22). There was no significant improvement in the change in lung function, hemodynamic parameters, clinical worsening, all-cause death, and serious adverse effects in the treated group compared to placebo.ConclusionPAH-specific therapy significantly improved exercise capacity in the patients with PH-ILD, but this is due to the greater contribution of the study with inhaled treprostinil. Therefore, our findings still did not support the routine use of the whole PAH-specific drugs for PH-ILD.

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Section: Discussionmentioning

confidence: 71%

PAH-specific therapy for pulmonary hypertension and interstitial lung disease: A systemic review and meta-analysis

Zhao

Zhang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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“…Historically multiple randomised controlled trials have investigated different therapeutic agents in PH-CLD as a whole against a variety of endpoints, with varying results and mixed evidence for therapeutic response ( 2 , 33 – 38 ). However, recently the INCREASE study demonstrated an improvement in 6MWD, NT-proBNP and clinical worsening in PH-CLD patients with ILD treated with inhaled treprostinil ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Non-invasive detection of severe PH in lung disease using magnetic resonance imaging

Alkhanfar

Dwivedi

Alandejani

et al. 2023

Front. Cardiovasc. Med.

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IntroductionSevere pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg) in chronic lung disease (PH-CLD) is associated with high mortality and morbidity. Data suggesting potential response to vasodilator therapy in patients with PH-CLD is emerging. The current diagnostic strategy utilises transthoracic Echocardiography (TTE), which can be technically challenging in some patients with advanced CLD. The aim of this study was to evaluate the diagnostic role of MRI models to diagnose severe PH in CLD.Methods167 patients with CLD referred for suspected PH who underwent baseline cardiac MRI, pulmonary function tests and right heart catheterisation were identified. In a derivation cohort (n = 67) a bi-logistic regression model was developed to identify severe PH and compared to a previously published multiparameter model (Whitfield model), which is based on interventricular septal angle, ventricular mass index and diastolic pulmonary artery area. The model was evaluated in a test cohort.ResultsThe CLD-PH MRI model [= (−13.104) + (13.059 * VMI)—(0.237 * PA RAC) + (0.083 * Systolic Septal Angle)], had high accuracy in the test cohort (area under the ROC curve (0.91) (p < 0.0001), sensitivity 92.3%, specificity 70.2%, PPV 77.4%, and NPV 89.2%. The Whitfield model also had high accuracy in the test cohort (area under the ROC curve (0.92) (p < 0.0001), sensitivity 80.8%, specificity 87.2%, PPV 87.5%, and NPV 80.4%.ConclusionThe CLD-PH MRI model and Whitfield model have high accuracy to detect severe PH in CLD, and have strong prognostic value.

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“…[4] The inconsistent conclusions could be a result of the theoretical concern that systemic administration of vasomodulating agents can worsen ventilation-perfusion mismatching due to increased intrapulmonary shunting, thus aggravating hypoxemia and worsening disease progression. [11,41,42] Intrapulmonary administration of PAH drugs by inhalation could address this issue, in which active agents only become available in best-ventilated lung units. [3,41] In the recently published INCREASE-trial from Waxman and colleagues, patients with ILD-PH treated with inhaled treprostinil had significant improvements in exercise capacity (the primary efficacy end point), as shown by clinically relevant changes in the 6-minute walk distance from baseline to week 16 between the two groups.…”

Section: Detection Of Ild-phmentioning

confidence: 99%

“…morphologic phenotyping and disease burden) and optimal staging could be the key to positive results. [42] Furthermore, shifting from medication with a predominantly vasodilator effect towards evaluation of innovative drugs that target vascular remodeling also of interest. [30]…”

Section: Detection Of Ild-phmentioning

confidence: 99%

Pulmonary hypertension in interstitial lung disease: an area of unmet clinical need

et al. 2022

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Pulmonary hypertension (PH) is present in an important proportion of patients with interstitial lung diseases (ILDs), encompassing a large, heterogeneous group of diffuse parenchymal lung diseases. Development of ILD-related PH is associated with reduced exercise capacity, increased need for supplemental oxygen, decreased quality of life and earlier death. Diagnosis of ILD-related PH is important and requires a high index of suspicion. Noninvasive diagnostic assessment can suggest the presence of PH, although right heart catheterization remains the gold standard to confirm the diagnosis and to assess its severity. A comprehensive assessment is needed to make sure reversible causes of PH have been ruled out, including thromboembolic events, untreated hypoxemia and sleep disordered breathing. The results of trials concerning pulmonary vasodilators in this particular patient group have been disappointing and, in some cases, were even associated with an increased risk of harm. Newer strategies such as medications administered through inhalation and combinations with antifibrotic drugs show encouraging results. Moreover, unraveling the role of the vasculature in the pathophysiology of pulmonary fibrosis and ILD-related PH may potentially unlock new therapeutic opportunities.

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

Cited by 4 publications

References 31 publications

PAH-specific therapy for pulmonary hypertension and interstitial lung disease: A systemic review and meta-analysis

PAH-specific therapy for pulmonary hypertension and interstitial lung disease: A systemic review and meta-analysis

Non-invasive detection of severe PH in lung disease using magnetic resonance imaging

Pulmonary hypertension in interstitial lung disease: an area of unmet clinical need

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