Properly Diagnosing Pulmonary Arterial Hypertension
Tufts University School of Medicine, Boston, Massachusetts. Electronic address: .The American journal of cardiology (Impact Factor: 3.28). 04/2013; 111(8 Suppl):2C-9C. DOI: 10.1016/j.amjcard.2013.01.318
Pulmonary hypertension (PH) is found in many clinical conditions and is associated with increased morbidity and mortality. Pulmonary arterial hypertension (PAH) is a clinical condition characterized by precapillary PH without causes such as lung disease, chronic thromboembolic PH, or other rare conditions. Evaluating a patient with suspected PH requires a series of investigations intended to confirm the diagnosis, determine the clinical PH group (and, in the case of PAH group 1, the specific etiology), and evaluate the functional and hemodynamic impairment. The workup should identify the risk factors for PH (e.g., left heart disease, lung diseases associated with alveolar hypoxia, and chronic thromboembolism) versus the conditions associated with PAH group 1 (e.g., scleroderma, human immunodeficiency virus, anorexigen use, liver disease). A detailed algorithm is presented to help physicians determine the appropriate PH category. Because the presence of one condition associated with PH does not exclude another etiologies, clinicians are strongly encouraged to follow the entire algorithm. Discussions and case studies are presented describing the differentiation of PAH group 1 from PH group 2 and PAH group 1 from PH group 3; diagnosing PH group 4; determining the long-term calcium channel blocker response in those with idiopathic PAH; and determining the severity of PH.
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ABSTRACT: Introduction: Pulmonary arterial hypertension (PAH) is a chronic disorder of the pulmonary vasculature characterized by elevated mean pulmonary arterial pressure eventually leading to right-sided heart failure and premature death. Macitentan is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with high affinity and sustained receptor binding that was approved in the USA, Europe, Canada, and Switzerland for the treatment of PAH. Areas covered: This review discusses the pharmacokinetics (PK) and pharmacodynamics (PD) of macitentan and its drug interaction potential based on preclinical and clinical data. Expert opinion: Up to date, macitentan is the only registered treatment for PAH that significantly reduced morbidity and mortality as a combined endpoint in a long-term event-driven study. The safety profile of macitentan is favorable with respect to hepatic safety and edema/fluid retention and may be better than that of other ET receptor antagonists such as bosentan and ambrisentan. The PK profile supports a once-a-day dosing regimen. Macitentan has limited interactions with other drugs. Based on these characteristics macitentan is an important new addition to the treatment of PAH.
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ABSTRACT: Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vascular system, which leads to right-sided heart failure and ultimately death if untreated. Treatments to regulate the pulmonary vascular pressure target the prostacyclin, nitric oxide, and endothelin (ET) pathways. Macitentan, an oral, once-daily, dual ETA and ETB receptor antagonist with high affinity and sustained receptor binding is the first ET receptor antagonist to show significant reduction of the risk of morbidity and mortality in PAH patients in a large-scale phase III study with a long-term outcome. Here we present a review of the available clinical pharmacokinetic, pharmacodynamic, pharmacokinetic/pharmacodynamic relationship, and drug-drug interaction data of macitentan in healthy subjects, patients with PAH, and in special populations.
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