An evidence-based approach to the management of pulmonary arterial hypertension

Abstract

The diagnostic criteria for pulmonary arterial hypertension should be revised to include PVR. Sildenafil's efficacy and price recommend it as a first-line oral therapy. New pulmonary arterial hypertension-regression therapies and therapeutic combinations offer the potential for cure of pulmonary arterial hypertension.

Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells

“…Trigger of EC proliferation and plexiform lesion formation by proliferating ECs are important pathological changes in PAH ( 18 ). However, whether EETs are responsible for the tumorlets of endothelial cells that obliterate pulmonary arteries, as well as the relative mechanisms, remains unclear.…”

Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility

“…In a double-blind randomized trial, Wilkins et al 35 showed that sildenafil (but not bosentan, an endothelin receptor antagonist also approved for the treatment of PAH) decreased RVH (studied by magnetic resonance imaging), although the relative importance of decreasing afterload versus direct antihypertrophic effects on the RV is difficult to determine in vivo. Because of its effectiveness, excellent toxicity profile, and relatively low price compared with the other available therapies, 36 sildenafil use is rapidly increasing in PAH patients, and its potential benefit in a number of cardiovascular disorders is being investigated.…”

Emerging Concepts and Translational Priorities in Pulmonary Arterial Hypertension

“…10 Oral therapies for PAH such as endothelin receptor antagonists (eg, bosentan) and phosphodiesterase inhibitors (eg, sildenafil) may improve symptoms and the quality of life of PAH patients, but it remains to be determined whether they improve survival. The overall improvement in hemodynamics is minimal, and the functional capacity improvement with these therapies is similar to improvements achieved by exercise training alone.…”

“…The overall improvement in hemodynamics is minimal, and the functional capacity improvement with these therapies is similar to improvements achieved by exercise training alone. 10,11 The ease of delivery of these therapies contributes to their heavy use. The emerging idea that the next breakthrough in management of PAH may be a combination of existing therapies is of concern if this in any way impedes the development of new testable ideas.…”

“…Only 3 abnormalities have been translated into clinical practice: the downregulation of the prostacyclin axis (reversed by exogenous prostacyclin analogues), the downregulation of the NO/ cGMP axis (reversed by inhaled NO and sildenafil), and the upregulation of the endothelin axis (reversed by endothelin receptor antagonists). 10 All of these therapies were developed on the basis of the "vasodilator" hypothesis of pulmonary hypertension. Despite the realization that PAH is not a disease of vascular tone (Ͻ10% of patients respond acutely to vasodilators), these therapies continue to dominate the field, although some of them were also, in retrospect, found to have some antiproliferative properties.…”