Effects of an olmesartan medoxomil based treatment algorithm on 24-hour blood pressure control in patients with hypertension and type 2 diabetes

Abstract

Objective:

The BENIFICIARY (BENIcar safety and efFICacy evaluatIon: An open-label, single-ARm, titration study in patients with hypertension and tYpe 2 diabetes) study was conducted to evaluate the efficacy and safety of olmesartan medoxomil (OM) plus hydrochlorothiazide (HCTZ) in patients with hypertension and type 2 diabetes.

Research design and methods:

After a placebo run-in period, 192 patients received OM 20 mg/day for 3 weeks. If blood pressure (BP) remained ≥120/70 mm Hg, patients were up-titrated to OM 40 mg/day for 3 weeks and subsequently (in 3-week intervals) to OM/HCTZ 40/12.5 mg/day, then OM/HCTZ 40/25 mg/day as necessary. Blood pressure was evaluated by mean 24-hour ambulatory BP monitoring (ABPM). The primary efficacy endpoint was the change in mean 24-hour ambulatory systolic BP (SBP) from baseline to Week 12. Secondary endpoints included: change in ambulatory diastolic BP (DBP) from baseline to Week 12; changes in ambulatory SBP and DBP during daytime, nighttime, and the last 2, 4, and 6 hours of the dosing interval; and achievement of prespecified ambulatory BP targets.

Clinical trials registry number:

NCT00403481.

Results:

Mean 24-hour ambulatory SBP and DBP decreased by 20.4 mm Hg and 11.1 mm Hg, respectively (both P < 0.0001 to baseline), and 61.6%, 47.1%, and 39.0% of patients reached the ambulatory BP targets of <130/80 mm Hg, <125/75 mm Hg, and <120/80 mm Hg, respectively. The study medication was well tolerated with few adverse events: 67/192 patients (34.9%) experienced a treatment-emergent adverse event (TEAE) while 15/192 (7.8%) experienced a drug-related TEAE.

Conclusions:

In this open-label ABPM study, an OM ± HCTZ based treatment regimen safely and significantly reduced BP in patients with hypertension and type 2 diabetes when assessed by 24-hour ABPM.

Key words::

• 24-hour blood pressure control
• Hypertension
• Olmesartan medoxomil
• Type 2 diabetes mellitus

Transparency

Declaration of funding

This study and the preparation of the manuscript was supported by Daiichi Sankyo, Inc.

Declaration of financial/other relationships

J.M.N. has disclosed he is a member of the speakers bureau for Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Pfizer, Daiichi Sankyo, Inc., and sanofi-aventis. D.J.K. is Medical Director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, which institution received significant research support from Daiichi Sankyo, Inc. as an enrolling site in this study. W.F.W., K.A.S., and A.S. are employees of, J.X. a consultant for, Daiichi Sankyo, Inc.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she has received clinical research funds from Novartis, Daiichi Sankyo and other pharmaceutical companies as a clinical investigator, as well as honoraria for speaking engagements. Peer Reviewer 2 has disclosed no relevant financial relationships.

Acknowledgments

We thank Jennifer M. Kulak, PhD, Alan J. Klopp, PhD, and Christopher J. Jones, PhD, of Wolters Kluwer, for providing editorial assistance in the preparation of this manuscript.

We thank the following participating investigators:

Gregory Collins, MD (Charlotte Clinical Research, Charlotte, NC); Charles H. DeBusk, MD (Heartland Medical, PC, New Tazewell, TN); Andrew Feldman, DO (University Clinical Research Deland, Deland, FL); Robert Frederickson, MD (Brookwood Internists, PC, Birmingham, AL); David Johnson, MD (Searcy Medical Center, Searcy, AR); Dean J. Kereiakes, MD (Lindner Clinical Trial Center, Cincinnati, OH); Marc Kozinn, MD (Cardiology & Internal Medicine, Williamsville, NY); Gregory Lakin, MD (Professional Research Network of Kansas, Wichita, KS); Andrew Lewin, MD (National Research Institute, Los Angeles, CA); Thomas Littlejohn, MD (Piedmont Medical Research Associates, Winston-Salem, NC); Barry Lubin, MD (Hampton Roads Center for Clinical Research Inc., Norfolk, VA); Nicholas Messina, MD (Vista Medical Research, Inc., Mesa, AZ); Bradley Musser, MD (Bexar Clinical Trials, Richardson, TX); Joel Neutel, MD (Orange County Research Center, Tustin, CA); Stephen Ong, MD (MD Medical Research, Oxon Hill, MD); Irwin Plisco, MD (Irwin S. Plisco, MD, Florissant, MO); Jaime Sandoval, MD (Padre Coast Clinical Research, Corpus Christi, TX); Robert Strzinek, MD (Texas FamiliCare Clinical Research, Colleyville, TX); Dan Sugimoto, MD (Cedar-Cross Research Center, Chicago, IL); Jeffrey Wayne, MD (Clinical Trials Research, Lincoln, CA); Robert Weiss, MD (Maine Research Associates, Auburn, ME); Larry I. Gilderman, MD (University Clinical Research, Inc., Pembroke Pines, FL); Daniel Yarrish, MD (Salt Lake Research, LLC, Salt Lake City, UT); Andrea Phillips, MD (Philips Medical Services, Jackson, MS).