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) ≥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.

Keywords:

• angiotensin receptor blocker (ARB)
• fixed-dose combination
• irbesartan/HCTZ
• severe hypertension

Acknowledgments

The authors would like to thank the participating study centers for their valuable involvement with this trial.

Declaration of Interest

This study was supported by the Bristol-Myers Squibb Sanofi-Synthelabo Partnership. J. M. Neutel is a member of the following speaker's bureaus: Novartis, Sanofi-BMS, Boehringer Ingelheim, Pfizer, Forest, Biovail and Sankyo. S. S. Franklin is a member of the following speaker's bureaus: Boehringer Ingelheim, Bristol-Myers Squibb, and Merck; and is a consultant for AtCor Medical and Bristol-Myers Squibb. A. Bhaumik and P. Lapuerta are employees of Bristol-Myers Squibb. S. Oparil is the recipient of grants-in-aid from Abbott Laboratories, Astra Zeneca, Aventis, Biovail, Boehringer Ingelheim, Bristol Myers-Squibb, Forest Laboratories, GlaxoSmithKline, Novartis, Merck & Co., Pfizer, Sankyo Pharma, Sanofi-Synthelabo, and Schering-Plough. She is a consultant for Bristol Myers-Squibb, Daiichi Sankyo, Merck & Co., Novartis, Pfizer, Sanofi Aventis, and The Salt Institute and is a member of the Board of Directors for Encysive Pharmaceuticals.