Simvastatin as a Treatment for 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.

Inclusion criteria

• Patients with idiopathic PAH or PAH related to collagen vascular disease
• Age 18 years or over
• Receiving conventional therapy with diuretics, digoxin, warfarin, sildenafil and bosentan. Stable for 1 month
• 6 minute walk distance between 150m and 450m
• Modified NYHA functional class II or III

Exclusion criteria

• PAH from a cause other than permitted by entry criteria
• Change in PAH treatment in past 4 weeks
• Patients requiring prostanoid therapy
• Patients already taking a statin
• Clinically significant disturbance of liver function - AST or ALT >3xULM; bilirubin >1.5xULM
• Contraindication for a magnetic resonance scan