Antihypertensive efficacy of olmesartan medoxomil or valsartan in combination with amlodipine: A review of factorial-design studies

ABSTRACT

Background: Most patients with hypertension require more than one drug to attain recommended blood pressure (BP) targets. Initiating therapy with two agents is recommended for patients at high risk of a cardiovascular event or with a BP > 20/10 mmHg above goal. Combination therapy is effective when comprised of agents with complementary mechanisms of action, such as calcium channel blockers (CCBs) and angiotensin II-receptor blockers (ARBs). Two fixed-dose CCB/ARB combinations are approved in the US: amlodipine/valsartan (AML/VAL) and amlodipine/olmesartan medoxomil (AML/OM).

Objectives: To review and describe the efficacy of AML/VAL and AML/OM combinations by discussing similarly designed clinical trials.

Methods: Three 8-week, randomized, double-blind, placebo-controlled, parallel-group factorial-design studies were examined (two AML/VAL; one AML/OM). The study endpoints presented in this review were: change from baseline in least-squares mean seated diastolic BP (SeDBP) and least-squares mean seated systolic BP (SeSBP). In addition to the efficacies of AML/VAL and AML/OM combinations, the efficacies of AML, VAL and OM administered as monotherapy are presented. Placebo-subtracted BP reductions were calculated for this review.

Results: Patient demographics were similar but mean baseline SeBP was higher in the OM study (163.8/101.6 mmHg) than in the VAL studies (152.8/99.3 and 156.7/99.1 mmHg), possibly suggesting that the OM study included a more difficult-to-treat patient population. AML/ARB combinations consistently produced greater mean SeBP reductions than monotherapy. Least squares (LS) mean SeDBP reductions were 19.4 mmHg (AML/OM 10/40 mg; placebo-corrected: 15.9 mmHg) and 18.6 mmHg (AML/VAL 10/320 mg; placebo-corrected: 9.8 mmHg). LS mean SeSBP reductions were 28.5 mmHg (AML/OM 10/40 mg; placebo-corrected: 25.7 mmHg) and 28.4 mmHg (AML/VAL 10/320 mg; placebo-corrected: 15.5 mmHg).

Conclusions: This review of published factorial-design studies showed that the maximal marketed doses of an amlodipine/olmesartan medoxomil combination (10/40 mg) and an amlodipine/valsartan combination (10/320 mg) produced large reductions in BP from baseline. Limitations of this review include the small number of studies analyzed and the inherent heterogeneity between patient populations. Further research is warranted to directly compare the efficacy of these combinations in a randomized, controlled trial, or additional published clinical trials are required to provide larger data sets for robust meta-analyses and to overcome heterogeneity observed within these studies.

Key words: :

• Amlodipine
• Factorial design
• Hypertension
• Olmesartan medoxomil
• Valsartan

Acknowledgments

Declaration of interest: Funding for editorial assistance was provided by Daiichi Sankyo, Inc. The authors thank Jennifer M. Kulak, PhD, and Christopher J. Jones, PhD, Wolters Kluwer Health, for their editorial assistance in the preparation of this manuscript. Figures 2 and 3 reprinted from Clin Ther, 29(4), Philipp T, et al, Two multicenter, 8-week, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension, 563-580, Copyright (2007), with permission from Excerpta Medica, Inc.