Efficacy and safety of darusentan in patients with resistant hypertension: results from a randomized, double-blind, placebo-controlled dose-ranging study.
In this phase 2, randomized, double-blind, placebo-controlled forced dose-titration study, 115 patients with resistant hypertension, receiving background therapy with >/=3 antihypertensive medications including a diuretic at full doses, were randomized 2:1 to increasing doses of darusentan (10, 50, 100, 150, and 300 mg), a selective endothelin receptor antagonist, or matching placebo once daily for 10 weeks. Darusentan treatment decreased mean systolic and diastolic blood pressure levels in a dose-dependent fashion compared with placebo; the largest reductions were observed at week 10 (300-mg dose) (systolic, -11.5+/-3.1 mm Hg [P=.015;] diastolic, -6.3+/-2.0 mm Hg [P=.002]). Darusentan (300 mg) also decreased mean 24-hour, daytime, and nighttime ambulatory blood pressures from baseline to week 10. Darusentan was generally well tolerated; mild to moderate edema and headache were the most common adverse events. This study demonstrates a clinical benefit from a new class of antihypertensive agent in patients classified as resistant by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines.
Black
Henry R
HR
New York University School of Medicine, New York, NY 10016, USA. hrbmd63@gmail.com
Bakris
George L
GL
Weber
Michael A
MA
Weiss
Robert
R
Shahawy
Mahfouz El
ME
Marple
Richard
R
Tannoury
Georges
G
Linas
Stuart
S
Wiens
Brian L
BL
Linseman
Jennifer V
JV
Roden
Robert
R
Gerber
Michael J
MJ
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010666:Phenylpropionates / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D065128:Endothelin Receptor Antagonists; D010666:Phenylpropionates; D011743:Pyrimidines; C107831:darusentan