The purpose of the study is to investigate the safety and efficacy of adding simvastatin to the current conventional treatment regimen for the management of pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is a disease that is characterised by progressive narrowing of the blood vessels of the lungs. This results in a pressure load on the heart and heart failure. The narrowing is in part due to constriction but mostly due to structural changes in affected vessels. The structural changes affect all cell components of the vessel wall (the endothelial lining, the muscle layer and fibrous tissue) and can lead to local clot formation. In addition there is evidence of inflammation of the vessels and what is known as oxidative stress. The disease may occur with no obvious cause, when it is known as idiopathic, but it can also be associated with a variety of other diseases, including congenital heart disease, collagen vascular disease and HIV infection. Current approaches to the treatment of pulmonary hypertension are unsatisfactory as they do not prevent disease progression and do not directly or adequately address many of the processes detailed above. Alternative or additional treatments are therefore required and an attrative approach is to use a statin (a 3-hydroxy-3-methylglutaryl-coenzymeA, or HMG-CoA, reductase inhibitor). Statins are widely used for their ability to lower blood cholesterol but increasing evidence indicates that these drugs also have direct effects on cell components of the vessel wall - including inhibiting inflammation, clot formation and oxidative stress - that might be beneficial in pulmonary hypertension.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
42
Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Placebo tablet once daily.
Department of Internal Medicine II, Klinikstrasse 36 D-35392
Giessen, Germany
Royal Brompton Hospital, Sydney Street
London, United Kingdom
Hammersmith Hospital, Du Cane Road
London, United Kingdom
Change in Right Ventricular Mass From Baseline
As measured by cardiac magnetic resonance (the study is powered to detect an 8.5g difference in RV mass between the two treatments, based on reproducibility measurements of RV mass in healthy volunteers and patients)
Time frame: 6 months post study treatment
Change in 6-minute Walk Distance
Change in distance achieved in 6 minute walk test from baseline
Time frame: 6 months
Change in LV Mass
Change in LV mass from baseline based on cardiac MRI
Time frame: 6 months
Circulating Levels of BNP
Change in NT-proBNP levels compared to baseline
Time frame: 6 months
Change in Quality of Life Score
Change in quality of life score from baseline as measured by Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) scored from 1-25, with higher scores indicating worse quality of life, the investigator reported the score change.
Time frame: 6 months
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