Study finds benefit from sildenafil in severe pulmonary hypertension

Study finds benefit from sildenafil in severe pulmonary hypertension

Jul 10 (HeartCenterOnline) - Sildenafil, a drug indicated for erectile dysfunction, has shown effectiveness in patients with pulmonary hypertension whose condition had not improved despite other treatments. The results are published in the July 2 issue of the Journal of the American College of Cardiology.

Pulmonary hypertension is characterized by high blood pressure ( hypertension) in the blood vessels that supply oxygen-poor blood to the lungs. The condition arises because the blood vessels of the lung (pulmonary arterioles) have narrowed, thus restricting blood flow. In response, pressure within the large artery from the lung to the heart (the pulmonary artery) can be elevated to over 30 millimeters of mercury (mm Hg) at rest.

As a result of pulmonary hypertension, the right side of the heart has a harder time pumping blood through the narrowed pulmonary artery and to the lungs. Eventually, it may become enlarged and weakened from the continuous effort. Consequently, untreated pulmonary hypertension can lead to a leaking valve on the right side of the heart (regurgitation) of the tricuspid valve), or complete right- side heart failure (cor pulmonale). A number of treatments for pulmonary hypertension are available. This includes oxygen-replacement therapy, by which people can get supplemental oxygen from either mobile or immobile oxygen canisters or tanks. Medications may also be prescribed to treat pulmonary hypertension, such as anticoagulants, calcium channel blockers, diuretics, vasodilators and prostacyclins.

In the current study, researchers from University Hospital in Giessen, Germany note that continuous intravenous infusion of prostacyclin has been a "life- saving therapy" in severe pulmonary hypertension. But it is not without its adverse side effects, such as the need for increased dosages, and complications from the intravenous line itself. An inhaled, aerosol formulation of prostacyclin, iloprost, provided similar benefit but without the side effects from infused prostacyclin. In some patients, however, the improvement in lung function and exercise capacity was temporary. The researchers sought to improve on the results seen with iloprost, drawing on earlier studies of sildenafil, a drug approved for erectile dysfunction. Those studies found that sildenafil, when combined with inhaled iloprost, resulted in enhanced vasodilation of the lungs. The current study went a st ep further, testing long-term sildenafil/iloprost treatment.

A group of 73 patients with pulmonary hypertension undergoing treatment with inhaled iloprost was selected from the researchers' referral center. Of these, 14 fulfilled the criteria of having worsening pulmonary hypertension despite "conventional treatment." These 14, in addition to the iloprost, received oral sildenafil over the following 9 to 12 months.

Prior to iloprost therapy alone, the average distance the patients were able to walk was approximately 700 feet within six minutes. This improved to about 1,000 feet with iloprost before falling back to about 850 feet. With the combined iloprost/sildenafil treatment, the distance was increased to over 1,100 feet for up to 12 months.

Said Dr. Hossein A. Ghofrani, lead author of the study, "The potential of sildenafil for the treatment of patients with pulmonary arterial hypertension, either as a single therapy or as an adjunct [combination] therapy, is very high." With the improvements in exercise capacity, sustained over a longer period of time, Dr. Ghofrani said that there "is reason to be optimistic about the long-term effectiveness of this therapy." He foresees "future therapeutic approaches [focusing] more and more on combination therapy with substances that are compatible."

For more information on this topic, visit HeartCenterOnline's Pulmonary Center.