SOURCES: Lewis Rubin, M.D., FACP, FCCP, emeritus professor, University of California, San Diego School of Medicine; Carl Pepine, M.D., MACC, past president, American College of Cardiology, and director emeritus, division of cardiovascular medicine, University of Florida College of Medicine, Gainesville; Aug. 27, 2015, New England Journal of Medicine
WEDNESDAY, Aug. 26, 2015 (HealthDay News) -- A combination treatment that includes the active ingredient in the erectile dysfunction drug Cialis may reduce death and hospitalization from an incurable lung disease that mainly affects women, a new clinical trial shows.
When combined with a blood pressure medication called ambrisentan (Letairis), a high dosage of tadalafil (Adcirca) significantly reduced the progression of pulmonary arterial hypertension, according to results published in the Aug. 27 issue of the New England Journal of Medicine. The condition involves high blood pressure in the arteries leading into the lungs.
Patients who took the combination therapy were half as likely to die, require hospitalization or have severe progression of their illness, when compared with people who only received one of the two drugs, researchers found. People using tadalafil for pulmonary arterial hypertension take 40 milligrams (mg) a day, while the dosage for erectile dysfunction runs between 2.5 mg and 20 mg a day.
The results were so encouraging that the marketer of ambrisentan in the United States has submitted a request to the U.S. Food and Drug Administration so this combination use can be added to the drug's label, said senior study author Dr. Lewis Rubin, an emeritus professor of medicine at the University of California, San Diego School of Medicine.
Dr. Carl Pepine, past president of the American College of Cardiology, said the results "offer an easy-to-use additional treatment for patients who have this unfortunate condition, who are largely women."
The two drugs work in different ways to ease the effects of pulmonary arterial hypertension, so researchers decided to see if their impact would be greater used in tandem, Rubin explained.
"This is a complex disease. There's no magic bullet," Rubin said. "We postulated that the more pathways you target, the better the effect would be."
Pulmonary arterial hypertension causes people to be chronically short of breath, as their blood has difficulty getting through the lungs to pick up oxygen. It eventually leads to heart failure because the heart has to pump harder to keep blood circulating through the body.
Pulmonary arterial hypertension is relatively rare, Rubin said, affecting about 50,000 people in the United States. Average survival is roughly two years following diagnosis.
Tadalafil works by blocking PDE5, an enzyme that breaks down a substance called nitric oxide that promotes dilation of blood vessels. With more nitric oxide available, the arteries feeding the lungs are better able to dilate, increasing blood flow.
Ambrisentan works by inhibiting endothelin, a substance that causes blood vessels to constrict, Rubin said. Thus, one drug promotes dilation of blood vessels while the other works to prevent constriction.
Researchers recruited 500 people with pulmonary arterial hypertension to take part in the clinical trial. The study involved 120 medical centers in 14 countries, and ran between October 2010 and July 2014.
About half of the study participants received both drugs, while one-quarter received the high dose of tadalafil alone and another quarter received ambrisentan alone.
Only about 18 percent of people on combination therapy died or experienced severe progression of pulmonary arterial hypertension, compared with 31 percent of people taking either ambrisentan or tadalafil alone, the study found.
And it appeared that using the two drugs together produced no additional side effects, Rubin and Pepine said.
"I was impressed with the relatively good tolerability," said Pepine, director emeritus of the cardiovascular medicine division at the University of Florida College of Medicine in Gainesville. "I think that will encourage us to use this combination treatment earlier in the course of the disease. It's possible we might be able to prevent these women from emerging into a very symptomatic stage, where their daily activities are greatly impaired."
The men taking the combination therapy also might derive other benefits from the tadalafil, given that the dosing is higher for pulmonary arterial hypertension than it is for erectile dysfunction, Rubin said.
"These are sick patients. It's not uncommon for the men to have erectile dysfunction because they're sick. Clearly, some of them are deriving some off-target benefits, if you will," Rubin said. "But their main focus is they can't breathe and their heart is giving out."
The clinical trial was funded by Gilead Sciences and GlaxoSmithKline, which sell ambrisentan in the United States and Europe, respectively.
For more on pulmonary arterial hypertension, visit the American Lung Association.