(Ivanhoe Newswire) -- A new drug, darusentan, reduces blood pressure
in patients who have not reached treatment goals with three or more
conventional antihypertensive drugs.
Professor Michael A Weber, State University of New York, Brooklyn, and
colleagues investigated blood-pressure-lowering effects of the new
endothelin type A antagonist, darusentan, in patients with
This study represents a new approach to treatment-resistant hypertension by
using a class of drugs called endothelin-receptor antagonists. The molecular
pathway involving endothelin type A is different from that targeted by
conventional blood pressure medications, such as blockers of the
renin-angiotensin system, diuretic drugs, and calcium-channel blockers.
This randomized, double-blind study was conducted in 117 sites in North and
South America, Europe, New Zealand, and Australia. A total of 379 patients
with systolic blood pressure of 140 more, who were receiving at least three
blood-pressure-lowering drugs, including a diuretic, at full or maximum
tolerated doses, were randomly assigned to 14 weeks' treatment with placebo
or darusentan. Changes in sitting systolic and diastolic blood pressures
were measured at baseline and at the end of treatment.
The mean reductions in systolic and diastolic blood pressures were
statistically significant with darusentan compared to placebo. The main
adverse effects of darusentan were related to fluid accumulation. Edema, or
fluid retention, occurred in 27 percent of patients given darusentan,
compared with 14 percent given placebo. One patient in the placebo group
died of sudden cardiac death, and five patients in the three darusentan dose
groups combined had cardiac-related serious adverse events.
According to the authors, "Darusentan provided meaningful lowering of
systolic and diastolic blood pressures in patients with treatment-resistant
hypertension already receiving many well chosen antihypertensive drugs.
Generally, darusentan was well tolerated, the main adverse effects being
related to fluid retention. The use of this drug accompanied by effective
diuretic therapy seems to represent a new and effective strategy for dealing
with treatment-resistant hypertension."
In an accompanying editorial, Dr Bryan Williams Department of Cardiovascular
Sciences and NIHR Cardiovascular Biomedical Research Unit, University of
Leicester, UK, was quoted as saying that Darusentan offers the potential for
a further . . . decrease in systolic blood pressure in people with resistant
hypertension, and appears to exert its effects regardless of gender, age,
and other concurrent treatments and diseases. But he added: "These findings
do not mean that darusentan would necessarily be the best treatment for
every patient with resistant hypertension. This important question can only
be addressed by further studies directly comparing various existing and
SOURCE: Lancet, September 11, 2009