Top

Clinical Drug Investigation

Published in:

01-02-2010 | Original Research Article

Efficacy and Tolerability of a Fixed-Dose Combination of Metoprolol Extended Release/Amlodipine in Patients with Mild-to-Moderate Hypertension

A Randomized, Parallel-Group, Multicentre Comparison with Losartan plus Amlodipine

Authors: Dr Anil Pareek, Nitin B. Chandurkar, Ravishankar Sharma, Dharmendra Tiwari, Bhagwan S. Gupta

Published in: Clinical Drug Investigation | Issue 2/2010

Abstract

Background: Epidemiological studies and clinical trials have shown that prevention of cardiovascular disease, the ultimate goal of hypertension treatment, requires a sufficient reduction in blood pressure.

Objective: The primary objective of this study was to compare the mean decrease in systolic (SBP) and diastolic (DBP) blood pressure between metoprolol extended release (XL)/amlodipine fixed-dose combination and losartan plus amlodipine combination in patients with mild-to-moderate essential hypertension. The secondary objectives of this study were to compare the proportion of responders in the two treatment groups and to evaluate the tolerability of the study medications.

Methods: This was a randomized, parallel-group, multicentre comparative study conducted at the outpatient departments of three teaching hospitals in India. Patients with mild-to-moderate hypertension (defined as DBP 90–109 mmHg) aged between 18 and 75 years were enrolled in this study and followed up for 12 weeks. Response to study treatments was evaluated in terms of mean decrease in SBP and DBP and the response rate (reduction to SBP <140 mmHg and DBP <90 mmHg).

Results: Out of 152 patients who underwent a 1-week placebo washout, 148 eligible patients were randomized to receive either metoprolol XL 25 mg/amlodipine 2.5 mg fixed-dose combination (76 patients) or losartan 25 mg plus amlodipine 2.5 mg (72 patients). The two treatment groups were similar with respect to demographic and baseline characteristics. Non-responders after 4 weeks of therapy were escalated to metoprolol XL 50 mg/amlodipine 5mg fixed-dose combination or losartan 50 mg plus amlodipine 5mg, respectively. The study was completed by 66 patients in each group, of whom 43 patients in each group responded to the starting doses. After 4 weeks’ therapy, both treatments were associated with significant decreases in SBP and DBP from baseline (p<0.001) and were comparable with respect to mean decrease in SBP (p = 0.304), mean decrease in DBP (p = 0.630) and response rate (p = 1.0). Also, both the step-up therapies were comparable with respect to mean decrease in SBP (p = 0.484), mean decrease in DBP (p = 0.650) and response rate (p = 0.134) at week 12. Both treatments were well tolerated in the studied population.

Conclusion: Metoprolol XL/amlodipine fixed-dose combination was found to be as effective and well tolerated as losartan plus amlodipine in the treatment of essential hypertension.

Sytkowski PA, D’Agostino RB, Belanger AJ, et al. Secular trends in long term sustained hypertension, long term treatment and cardiovascular mortality: the Framingham Heart Study 1950 to 1990. Circulation 1996; 93: 697–703PubMedCrossRef

MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke and coronary heart disease. Part I. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335(8692): 765–74PubMedCrossRef

Japanese Society of Hypertension. Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2004). Hypertens Res 2006; 29(Suppl.): S1–105CrossRef

Chobanian AV, Bakris GL, Black HR, et al., National Heart, Lung and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289: 2560–72PubMedCrossRef

European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–53CrossRef

Whitworth JA, World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens} 2003}; 21}: 1983–92PubMedCrossRef

Guidelines Subcommittee: 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. J Hypertens 1999; 17: 151–83

Saito I, Saruta T, ADVANCE-Combi study group. Controlled-release nifedipine and valsartan combination therapy in patients with essential hypertension: the Adalat CR and valsartan cost-effectiveness combination (ADVANCE-Combi) study. Hypertens Res} 2006}; 29}: 789–96PubMedCrossRef

Haria M, Plosker GL, Markham A. Felodipine/metoprolol: a review of the fixed dose controlled release formulation in the management of essential hypertension. Drugs 2000 Jan; 59(1): 141–57PubMedCrossRef

10.

Menard J. Clinical assessment of combination therapy development. Blood Press 1993; 2Suppl. 1: 5–9

11.

Maclean D, Mitchell ET, Irvine RL, et al. Comparison of once daily atenolol, nitrendipine and their combination in mild to moderate essential hypertension. Br J Clin Pharm 1990; 29: 455–63CrossRef

12.

Brown MJ, Cruickshank JK, MacGregor GA, et al. Better blood pressure control: how to combine drugs. J Hum Hypertens 2003; 17: 81–6PubMedCrossRef

13.

Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke and coronary heart disease. Part 2. Short term reductions in blood pressure: overview of randomized drug trials in their epidemiological context. Lancet 1990; 335: 827–38PubMedCrossRef

14.

Sica DA. Fixed-dose combination of antihypertensive drugs: do they have a role in rational therapy? Drugs 1994; 48: 16–24PubMedCrossRef

15.

Kohlman O, Oigman W, Mion D, et al. The “LOTHAR” study: evaluation of efficacy and tolerability of the fixed combination of amlodipine and losartan in the treatment of essential hypertension. Arg Bras Cardiol 2006; 86(1): 39–51CrossRef

16.

Neutel JM, Littlejohn TW, Chrysant SG, et al., on behalf of the Telmisartan Study Group. Telmisartan/hydrochlorothiazide in comparison with losartan/hydrochlorothiazide in managing patients with mild-to-moderate hypertension. Hypertens Res} 2005}; 28}: 555–63PubMedCrossRef

17.

Lacourciere Y, Gil-Extremera B, Mueller O, et al. Efficacy and tolerability of fixed-dose combinations of telmisartan plus HCTZ compared with losartan plus HCTZ in patients with essential hypertension. Int J Clin Pract 2003; 57(4): 273–9PubMed

18.

Saruta T, Ogihara T, Matsuoka H, et al. Antihypertensive efficacy and safety of fixed-dose combination therapy with losartan plus hydrochlorothiazide in Japanese patients with essential hypertension. Hypertens Res 2007; 30: 729–39PubMedCrossRef

19.

Shen F, Xie H, Ling G, et al. Synergistic effects of atenolol and amlodipine for lowering and stabilizing blood pressure in 2K1C renovascular hypertensive rats. Acta Pharmacologica Sinica 2005; 26: 1303–8PubMedCrossRef

20.

Bangalore S, Kamalakkannan G, Parkar S, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Evid Based Med 2008 Feb; 13(1): 18CrossRef

Title: Efficacy and Tolerability of a Fixed-Dose Combination of Metoprolol Extended Release/Amlodipine in Patients with Mild-to-Moderate Hypertension
A Randomized, Parallel-Group, Multicentre Comparison with Losartan plus Amlodipine
Authors: Dr Anil Pareek
Nitin B. Chandurkar
Ravishankar Sharma
Dharmendra Tiwari
Bhagwan S. Gupta
Publication date: 01-02-2010
Publisher: Springer International Publishing
Published in: Clinical Drug Investigation / Issue 2/2010
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI: https://doi.org/10.2165/11531770-000000000-00000

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Efficacy and Tolerability of a Fixed-Dose Combination of Metoprolol Extended Release/Amlodipine in Patients with Mild-to-Moderate Hypertension

A Randomized, Parallel-Group, Multicentre Comparison with Losartan plus Amlodipine

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2010

Cost Effectiveness of Atorvastatin in Patients with Type 2 Diabetes Mellitus

Associations between the C677T and A1298C Polymorphisms of MTHFR and the Efficacy and Toxicity of Methotrexate in Rheumatoid Arthritis

Cost Effectiveness of a Lidocaine 5% Medicated Plaster Compared with Pregabalin for the Treatment of Postherpetic Neuralgia in the UK

Safety and Efficacy of Desloratadine in Subjects with Seasonal Allergic Rhinitis or Chronic Urticaria

Impact of Adherence to Interferons in the Treatment of Multiple Sclerosis