The intravenous use of epoprostenol increased three-year survival rates by up to 80 percent and nearly doubled exercise tolerance. Doctors have known that epoprostenol extends PPH survival, but its longer-term benefits had not been clearly defined.
"We now have clear evidence of the effectiveness of epoprostenol in treating this rare, fatal disease. Awareness needs to be raised among clinicians seeing patients with symptoms that could be PPH," says lead researcher Vallerie V. McLaughlin, M.D., an assistant professor of medicine at Rush-Presbyterian-St. Luke's Medical Center in Chicago.
Primary, or unexplained, pulmonary hypertension is a rare lung disorder in which the blood pressure in the pulmonary arteries rises far above normal levels for no apparent reason. This abnormally high pressure is associated with changes in the small blood vessels in the lungs that increase resistance to blood flow.
When the smaller blood vessels in the lungs become more resistant to blood flow, the heart's right ventricle must work harder to pump enough blood through the lungs.
Epoprostenol is marketed in the United States as Flolan® by Glaxo-Smith-Kline and is also known as PGI 2. It works by relaxing blood vessels, thereby increasing the supply of blood to the lungs and reducing the heart's workload.
The National Institutes of Health established a PPH registry in 1980 describing clinical manifestations and survival rates. The registry demonstrated that the disease is difficult to diagnose and deadly. The average time from the start of symptoms until diagnosis was nearly three years. Mean survival was 2.8 years after diagnosis.
The Food and Drug Administration approved epoprostenol to treat the progression of advanced PPH in 1995. Later, an indication to treat other types of pulmonary hypertension was added.
Using a customized patient database, McLaughlin and colleagues tracked survival of 162 patients (mean age 42, and three times as many women) with severe PPH. Patients received a continuous infusion of epoprostenol via a portable infusion pump. When needed, they also received conventional treatments such as anticoagulants, diuretics and heart failure drugs.
Doctors monitored patients with periodic heart catheterizations. Baseline predictive values were established for each patient's exercise tolerance, level of heart function, right atrial pressure, and response to the vasodilating agent adenosine.
They found that one-year survival was 88 percent, two-year survival was 76 percent and three-year survival was 63 percent. This was significantly better than the expected survival rates of 59 percent at one year, 46 percent at two years and 35 percent at three years, for similar patients that was reported by the NIH registry.
Survival predictors after the first year included level of heart function, improvement in exercise tolerance, cardiac index, and mean pulmonary artery pressure. Senior investigator, Stuart Rich, M.D., professor of medicine at Rush-Presbyterian-St. Luke's Medical Center, suggests that such data is useful in determining which patients will do well long-term with epoprostenol and which need more advanced therapies such as lung transplantation.
McLaughlin, who is also assistant director of the Center for Pulmonary Heart Disease at Rush, urges wider application of epoprostenol therapy because PPH patients are often young adults.
"It is important to remember that this is a very young group of patients; most are women between the ages of 25 and 40 with a full life ahead of them. Although side effects were common, those that did occur were relatively minor -mostly infections around the injection site."
In the United States, an estimated 500 to 1,000 new cases of PPH are diagnosed each year, according to American Heart Association statistics.
Statistician Alicia Shillington was also a co-author.
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