DORADO: Darusentan lowered BP in patients with resistant hypertension

Edema and fluid retention were most frequently reported adverse events.

American Society of Hypertension 24th Annual Scientific Meeting

Darusentan, an oral endothelin antagonist taken once daily, was effective at lowering blood pressure in patients with resistant hypertension.

Researchers for the DORADO trial enrolled 379 patients with resistant hypertension and assigned them to either 50 mg (n=81), 100 mg (n=81) or 300 mg (n=85) of darusentan (Gilead Sciences) or placebo (n=132). They followed the patients for 14 weeks.

The researchers reported mean reductions in sitting systolic and diastolic BP compared with baseline. Patients in the 50 mg group had a mean systolic BP reduction of 16.5 mm Hg (P<.001). Patients in the both the 100 mg group and the 300-mg group had a mean systolic reduction of 18.1 mm Hg (P<.001). Mean reductions in sitting diastolic BP were 10.1 mm Hg (P<.001) in the 50 mg group, 9.9 mm Hg in the 100 mg group (P<.001) and 10.7 in the 300 mg group (P<.001). The researchers also reported reductions in 24-hour systolic and diastolic BP in all darusentan groups versus placebo (P<.001 for all comparisons). The most common adverse event was edema. Cardiovascular events occurred in five patients taking darusentan, including one incident of recurrent heart failure and two myocardial infarctions.

“Darusentan produced robust decreases in office and ambulatory BP when added to three or more antihypertensive medications, and about half of these treatment-resistant patients achieved BP goals,” Michael A. Weber, MD, a professor of medicine at the State University of New York Downstate Medical College in New York, said during his presentation. “We can conclude that that darusentan provides clinically meaningful improvements in BP control in patients with treatment-resistant hypertension.”

George L. Bakris, MD, professor of medicine and director of the hypertensive diseases unit at the University of Chicago, as well as a co-author of the study, feels that the drug will be helpful for the treatment of many patients with resistant hypertension but without heart failure.

“This was not monotherapy versus placebo. This was triple therapy versus placebo versus this drug,” Bakris, a member of the Endocrine Today editorial board, said. “In that context, I would say that we now have an additional tool in the armamentarium for treating resistant hypertension.” – by Eric Raible

For more information:

Weber M. LB-OR-06. Presented at: American Society of Hypertension 29th Annual Scientific Meeting and Exposition; May 6-9, 2009; San Francisco.