Spironolactone Combined With Captopril and Carvedilol for the Treatment of Pulmonary Arterial Hypertension
The purpose of this study is to determine whether a larger dose of the aldosterone antagonist spironolactone combined with an ACE inhibitor (captopril) and a beta-blocker (carvedilol) is effective in reverse pulmonary artery remodeling in patients with pulmonary arterial hypertension (PAH)secondary to congenital heart disease
The pathogenesis of PAH involves multiple mechanisms. However, three common factors are thought to cause the increased pulmonary vascular resistance that characterizes this devastating disease: vasoconstriction, pulmonary vascular proliferation and remodeling, and thrombosis in situ. Advances in our knowledge of the molecular mechanisms involved in PAH suggest that endothelial dysfunction with chronic impaired production of vasoactive mediators plays a key role. Reduced production of vasoactive mediators, such as nitric oxide (NO) and prostacyclin, along with prolonged overexpression of vasoconstrictors such as endothelin-1 (ET-1), not only affect vascular tone but also promote vascular remodeling. Thus, these substances represent logical pharmacological targets. Animal studies showed ET-1 could stimulate aldosterone secretion in different species, both in vivo and in vitro. This stimulation involves the ET-B alone and both ET-A and ET-B receptor subtypes in rats and humans. Animal studies also showed spironolactone combined with ACE inhibitor could normalize blood pressure, prevents upregulation of vascular ET-1, restore nitric oxide (NO)-mediated endothelial dysfunction. Beta-blockers have ability to reduce dp/dt in pulmonary artery, as well as left ventricle, thus prevent further damage to the dysfunctional endothelium. Furthermore, we observed from our practice that the aforementioned therapy could lower pulmonary artery pressure in patents with pulmonary hypertension secondary to left ventricular dysfunction. Thus, we hypothesize spironolactone combined with ACE inhibitor and beta-blocker has the ability to reverse remodeling of pulmonary artery in PAH patients.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
spironolactone captopril carvedilol
The First Hospital of Hebei Medical University
Hebei Medical University
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00240656
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Pulmonary Heart Disease
Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.
A multisystemic disorder characterized by a sensorimotor polyneuropathy (POLYNEUROPATHIES), organomegaly, endocrinopathy, monoclonal gammopathy, and pigmentary skin changes. Other clinical features which may be present include EDEMA; CACHEXIA; microangiopathic glomerulopathy; pulmonary hypertension (HYPERTENSION, PULMONARY); cutaneous necrosis; THROMBOCYTOSIS; and POLYCYTHEMIA. This disorder is frequently associated with osteosclerotic myeloma. (From Adams et al., Principles of Neurology, 6th ed, p1335; Rev Med Interne 1997;18(7):553-62)
A malformation of the heart in which the embryonic common PULMONARY VEIN was not incorporated into the LEFT ATRIUM leaving behind a perforated fibromuscular membrane bisecting the left atrium, a three-atrium heart. The opening between the two left atrium sections determines the degree of obstruction to pulmonary venous return, pulmonary venous and pulmonary arterial hypertension.
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