NEW YORK (Reuters Health) – Darusentan, a selective endothelin-receptor blocker, can reduce blood pressure in patients who have not reached their target levels using three or more antihypertensive agents, according to a report in the September 14th online issue of The Lancet.

“The use of this drug accompanied by effective diuretic therapy seems to represent a new and effective strategy for dealing with treatment-resistant hypertension,” Dr. Michael A. Weber, from the S.U.N.Y. Downstate Medical Center in Brooklyn, New York and colleagues state.

The findings are from an international study of 379 patients who were randomized to receive darusentan once a day, at a dose of 50, 100, or 300 mg, or placebo for 14 weeks. Subjects had systolic blood pressure of at least 140 mmHg (or at least 130 mmHg if they had diabetes or kidney disease) despite use of at least three antihypertensive agents at full or maximum tolerated doses.

The average reductions in systolic and diastolic blood pressures with placebo were 9 and 5 mmHg, respectively. By contrast, with darusentan the corresponding reductions were about 18 and 10 mmHg, regardless of which dose was used (p < 0.0001). The most common side effect with darusentan was fluid accumulation, seen in 27% of patients given the drugs versus 14% in those who received placebo. One sudden cardiac death occurred in the placebo group. Five patients in the combined darusentan groups experienced serious cardiac-related adverse events, including MI, atrial fibrillation, and heart failure. In a related editorial, Dr. Bryan Williams, from the University of Leicester, UK, comments that while encouraging, the current 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 newer treatments, especially further diuretic therapy and including recently reported non-pharmacological treatments.” Funding for the study was provided by Gilead Sciences, which gathered and analyzed the data. Reference:
Lancet 2009.