PD16 Riociguat In Pulmonary Arterial Hypertension: A Systematic Review

2018 ◽  
Vol 34 (S1) ◽  
pp. 135-136
Author(s):  
Gabriela Mosegui ◽  
Cid Vianna ◽  
Gabrielle Faria ◽  
Cristiano Tavares ◽  
Benedito Cordeiro
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pharmacological Treatment ◽  
Functional Class ◽  
Pulmonary Arterial ◽  
Clinical Worsening

Introduction:Pulmonary Hypertension is a silent disease and its diagnosis often occurs when it is already at an advanced stage. Pharmacological treatment of Pulmonary Arterial Hypertension (PAH) can be performed with: calcium channel blockers; phosphodiesterase-5 inhibitors; prostanoids; endothelin-receptor antagonists; and, soluble guanylate cyclase stimulators. The use of Riociguat was approved in Brazil by the National Sanitary Surveillance Agency on October 5, 2015 for use in patients with PAH. The objective was to perform a systematic review (SR) of the efficacy of pharmacological treatment of Pulmonary Arterial Hypertension comparing Riociguat with other available medications or with placebo.Methods:Following the steps described in the PRISMA guideline, a search for randomized controlled clinical trials was conducted, in which Riociguat was used alone or in combination with other therapies, in databases MEDLINE, LILACS, Web of Science, Science Direct, Cochrane Library Wiley and in the gray literature (Google Scholar, Capes Bank of Theses and Clinical Trials). EndNote and Mendeley were used as reference managers. Outcomes analyzed were: death; six-minute walk distance (6MWD); World Health Organization (WHO) functional class (improvement, stabilization or worsening); hemodynamic variables (pulmonary vascular resistance, cardiac index and pulmonary-artery pressure); clinical worsening; hospitalization; and, quality of life.Results:Four hundred and sixty-seven articles were obtained which reduced to 379 after the duplicated articles were removed. After exclusion by title and abstract by two independent reviewers, forty-seven studies remained. Through the gray literature, six studies were obtained, resulting in fifty-three articles being retrieved for full-text review. Five studies were selected to compose the SR. Compared with placebo, Riociguat showed improvements in 6MWD, pulmonary vascular resistance, WHO functional class and time to clinical worsening. Efficacy was maintained after one year of use. Subgroup analysis was performed comparing of treatment-naive patients and patients on background PAH-targeted therapy.Conclusions:This work may be used as a management and decision support tool, based on the same methodology of a Health Technology Assessment, and may contribute to quality decisions to be taken in relation to the incorporation of new technology.

scholarly journals Pulmonary arterial hypertension with below threshold pulmonary vascular resistance

2020 ◽  
Vol 56 (1) ◽  
pp. 1901654 ◽  
Author(s):  
Seshika Ratwatte ◽  
James Anderson ◽  
Geoffrey Strange ◽  
Carolyn Corrigan ◽  
Nicholas Collins ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Functional Class ◽  
Response To Therapy ◽  
Nyha Functional Class ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Pulmonary Arterial

Pulmonary vascular resistance (PVR) >3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wood units.Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25–30 mmHg), PAWP 13 mmHg (IQR 11–14 mmHg) and PVR 2.2 Wood units (IQR 1.9–2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280–416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7–96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32–101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).Patients with precapillary PH and “borderline” PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.

scholarly journals Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 779
Author(s):  
Daria S. Kostyunina ◽  
Paul McLoughlin
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Sex Chromosomes ◽  
Bone Morphogenetic Protein 2 ◽  
Sex Dimorphism ◽  
Pulmonary Arterial ◽  
The Impact

Pulmonary hypertension (PH) is a condition characterised by an abnormal elevation of pulmonary artery pressure caused by an increased pulmonary vascular resistance, frequently leading to right ventricular failure and reduced survival. Marked sexual dimorphism is observed in patients with pulmonary arterial hypertension, a form of pulmonary hypertension with a particularly severe clinical course. The incidence in females is 2–4 times greater than in males, although the disease is less severe in females. We review the contribution of the sex chromosomes to this sex dimorphism highlighting the impact of proteins, microRNAs and long non-coding RNAs encoded on the X and Y chromosomes. These genes are centrally involved in the cellular pathways that cause increased pulmonary vascular resistance including the production of reactive oxygen species, altered metabolism, apoptosis, inflammation, vasoconstriction and vascular remodelling. The interaction with genetic mutations on autosomal genes that cause heritable pulmonary arterial hypertension such as bone morphogenetic protein 2 (BMPR2) are examined. The mechanisms that can lead to differences in the expression of genes located on the X chromosomes between females and males are also reviewed. A better understanding of the mechanisms of sex dimorphism in this disease will contribute to the development of more effective therapies for both women and men.

scholarly journals Pulmonary Hypertension Due to Left Heart Disease

Hypertension ◽  
2020 ◽  
Vol 75 (6) ◽  
pp. 1397-1408 ◽  
Author(s):  
Mohammed S. Al-Omary ◽  
Stuart Sugito ◽  
Andrew J. Boyle ◽  
Aaron L. Sverdlov ◽  
Nicholas J. Collins
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Left Atrial ◽  
Left Atrial Pressure ◽  
Left Heart ◽  
Pulmonary Arterial

Pulmonary hypertension (PH) due to left heart disease (LHD) is the most common type of PH and is defined as mean pulmonary artery systolic pressure of >20 mm Hg and pulmonary capillary wedge pressure >15 mm Hg during right heart catheterization. LHD may lead to elevated left atrial pressure alone, which in the absence of intrinsic pulmonary vascular disease will result in PH without changes in pulmonary vascular resistance. Persistent elevation in left atrial pressure may, however, also be associated with subsequent pulmonary vascular remodeling, vasoconstriction, and an increase in pulmonary vascular resistance. Hence, there are 2 subgroups of PH due to LHD, isolated postcapillary PH and combined post- and precapillary PH, with these groups have differing clinical implications. Differentiation of pulmonary arterial hypertension and PH due to LHD is critical to guide management planning; however, this may be challenging. Older patients, patients with metabolic syndrome, and patients with imaging and clinical features consistent with left ventricular dysfunction are suggestive of LHD etiology rather than pulmonary arterial hypertension. Hemodynamic measures such as diastolic pressure gradient, transpulmonary gradient, and pulmonary vascular resistance may assist to differentiate pre- from postcapillary PH and offer prognostic insights. However, these are influenced by fluid status and heart failure treatment. Pulmonary arterial hypertension therapies have been trialed in the treatment with concerning results reflecting disease heterogeneity, variation in inclusion criteria, and mixed end point criteria. The aim of this review is to provide an updated definition, discuss possible pathophysiology, clinical aspects, and the available treatment options for PH due to LHD.

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