As yet unapproved, darusentan works in different way than standard medicines
SUNDAY, Sept. 13 (HealthDay News) -- A new drug for people whose high blood pressure cannot be controlled by existing medications has done well in a pivotal trial, researchers report.
Substantial reductions in blood pressure were achieved with various doses of the drug, darusentan, for people who were still hypertensive despite trying three or more medications, said a report released online Sept. 13 in The Lancet.
An effective new drug against resistant high blood pressure could be "potentially enormously beneficial," said one expert, Dr. Kirk Garratt, clinical director of interventional cardiovascular research at Lenox Hill Hospital in New York City.
The blood pressure drops seen in the study are highly encouraging, Garratt said. "It only takes small changes in blood pressure readings to confer benefits on patients," he noted. "This drug potentially takes people from a very dangerous place to a very safe place."
The study results will be submitted to the U.S. Food and Drug Administration as part of an application for marketing approval, said Nathan Kaiser, a spokesman for Gilead Sciences, the company that is developing the drug.
"A larger trial completed enrollment earlier this year," Kaiser said. "We expect data from that trial by the end of the year. Pending results of that second study, the earliest time we can apply for approval appears to be the fourth quarter of 2010."
Some studies have said that as many as 30 percent of people with high blood pressure, a major risk factor for cardiovascular problems such as heart attack and stroke, have the resistant form, in which blood pressure cannot be brought down to desired levels despite use of three or more drugs.
Darusentan acts to block the activity of endothelin, an artery-narrowing molecule. Its action involves a different molecular pathway than those targeted by conventional blood pressure medications, such as calcium channel blockers and diuretics.
The study, done at 117 sites across the globe, enrolled 379 people with systolic blood pressure (the higher number in a reading) that remained at 140 or higher (130 for those with diabetes or chronic kidney disease). The recommended blood pressure reading is 120/80. All patients received 14 weeks of treatment with daily doses of 50, 100 or 300 milligrams of darusentan, or a placebo, an inactive substance.
On average, the participants' systolic blood pressure dropped 17 points with the 50-milligram dose of darusentan and 18 points with both the 100-milligram and the 300-milligram dose. A 9-point drop was recorded in the placebo group.
"That was a very meaningful reduction in blood pressure," said study lead author Dr. Michael A. Weber, professor of medicine in the cardiology division of State University of New York, Downstate College of Medicine. "Even if you subtract what happened in the placebo group, you still get about a 10-point drop, which is a clinically important finding. It translates into a meaningful reduction in the likelihood of strokes and other cardiovascular outcomes."
The major side effect was edema, excess fluid accumulation, which occurred in 27 percent of people taking the active drug and 14 percent of those taking placebo.
Because of edema, "to be really effective, darusentan probably should be used along with effective diuretic therapy," Weber said. Diuretics, which increase the flow of fluid from the body, are already widely used against high blood pressure.
If darusentan works as hoped, it will be especially useful for older people with resistant high blood pressure, Weber said. "They tend to be middle-aged or older, often with some impairment of kidney function," he said. "It is harder and harder to treat them and even more necessary to get their blood pressure treated, so new and more effective tools will be even more valuable."
There's more on resistant high blood pressure at the American Heart Association.
SOURCES: Kirk Garratt, M.D., clinical director, interventional cardiovascular research, Lenox Hill Hospital, New York City; Nathan Kaiser, spokesman, Gilead Sciences, Foster City, Calif.; Michael A. Weber, M.D., professor of medicine, cardiology division, State University of New York, Downstate College of Medicine, Brooklyn, N.Y.; Sept. 13, 2009 The Lancet, online
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