title: Safety and tolerability of fixed-dose irbesartan/hydrochlorothiazide for rapid control of severe hypertension.
abstract: This prospective, double-blind, multicenter trial compared the safety and tolerability of irbesartan/hydrochlorothiazide (HCTZ) fixed-dose combination therapy with irbesartan monotherapy in patients with severe hypertension (seated diastolic blood pressure (SeDBP) >or=110 mm Hg, mean BP 172/113 mm Hg at baseline). Patients were randomized 2:1 to 7 weeks' irbesartan/HCTZ 150/12.5 mg to 300/25 mg (n = 468) or irbesartan 150 mg to 300 mg (n = 227). The incidence of treatment-related adverse events (AEs) was similar with combination and monotherapy (11.3% and 10.1%), and most AEs were mild-to-moderate. The combined incidence of prespecified AEs was lower with irbesartan/HCTZ than with irbesartan (8.8% vs. 11.5%). There were no treatment-related serious AEs or deaths. At week 5, more patients achieved SeDBP < 90 mm Hg compared to irbesartan (47% vs. 33%; P = 0.0005). Despite more rapid and aggressive BP lowering, initial fixed-dose irbesartan/HCTZ demonstrated a comparable AE profile to irbesartan monotherapy in patients with severe hypertension.
authors.affiliation: Orange County Research Center, Tustin, CA 92780, USA. JMNeutel@aol.com
authors.forename: Joel M
authors.initials: JM
authors.lastname: Neutel
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Franklin
authors.forename: Amitabha
authors.initials: A
authors.lastname: Bhaumik
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapuerta
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004338:Drug Combinations; D049993:Sodium Chloride Symporter Inhibitors; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000077405:Irbesartan