In a newly reported study, patients whose blood pressure remained high despite very aggressive treatment had significant reductions in both the top (systolic) and bottom (diastolic) blood pressure numbers by adding the drug darusentan to the mix.
The drug works in a novel way by blocking the production of the amino acid endothelin within the walls of the artery. Endothelin is believed to raise blood pressure by causing the blood vessels to constrict.
"When you block endothelin the arteries relax and blood pressure should drop," researcher Michael A. Weber, MD, of the State University of New York, tells WebMD.
Blood Pressure Dropped by 10 Points
Weber led the study, which included 379 patients treated at 117 sites in North and South America, Europe, New Zealand, and Australia.
All of the patients had elevated blood pressure despite treatment with at least three blood pressure medications, including a diuretic ("water pill") at the highest dose the patient could tolerate.
In addition to these treatments, the patients received either a placebo or darusentan for 14 weeks at doses of 50 milligrams, 100 milligrams, or 300 milligrams taken once per day.
Blood pressure was measured in all patients at the beginning and end of the 14-week study.
Compared to placebo, the experimental drug was found to reduce systolic blood pressure by an additional 10 points.
This was true for all patients regardless of the dose of the experimental drug they took, how sick they were, and what other drugs they were on.
The main side effect of treatment was fluid retention, reported in 27% of the darusentan patients and 14% of patients in the placebo arm of the study.
Weber says this side effect can be avoided in most patients by prescribing a more powerful diuretic than is typically given, but he adds that patients with heart failure should not take darusentan because of this side effect.
"The size of the [blood pressure lowering] effect with this drug was really encouraging," Weber says. "For many people with treatment-resistant hypertension, adding this drug to the drugs they are taking would be all they would need to do to get their blood pressure down to where it needs to be."
Second Trial to Be Reported
The study, which appears online in The Lancet, was funded by the drugmaker Gilead Sciences. The company is expected to seek FDA approval for darusentan as a treatment for resistant hypertension sometime next year.
Gilead spokesman Nathan Kaiser tells WebMD that results from a much larger trial of the drug should be made public by the end of 2009.
In that trial, darusentan is being compared to the drug Tenex, which is often prescribed to patients who fail to achieve target blood pressure goals with conventional treatments.
In an editorial published with the study, blood pressure researcher Bryan Williams, MD, of England's University of Leicester, writes that important questions remain about the experimental drug.
"These findings do not mean that darusentan would necessarily be the best treatment for every patient with resistant hypertension," he writes.
In an interview with WebMD, Williams notes that more study is needed to identify better treatments and treatment strategies for lowering blood pressure in patients with hard-to-manage hypertension.
"It is unlikely that a single treatment strategy is going to be the best for everybody, and while this drug may be perfect for some, there may be others who might respond better to different treatment options," he says.
The problem, he adds, is that these other treatment options have not been as thoroughly studied.