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Combination Therapy with Candesartan Cilexetil 32mg and Hydrochlorothiazide 25mg Provides the Full Additive Antihypertensive Effect of the Components

A Randomized, Double-Blind, Parallel-Group Study in Primary Care

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Abstract

Background and objective: Fixed-combination tablets of candesartan (orally administered as the pro-drug candesartan cilexetil and hereafter referred to as candesartan) and hydrochlorothiazide (HCTZ) 8/12.5mg and 16/12.5mg are effective and well tolerated. However, some patients require higher doses to attain target blood pressure, and combination tablets containing candesartan and HCTZ at the upper end of their respective dose ranges are now being developed. This study aimed to assess the antihypertensive effect and tolerability of the combination of candesartan 32mg and HCTZ 25mg versus candesartan 32mg monotherapy, HCTZ 25mg monotherapy, and placebo.

Methods: This was a randomized, double-blind, parallel-group study, with 8 weeks of follow-up, carried out in primary-care outpatients. 1524 men or women (age 20–80 years) with mild to moderate primary hypertension and sitting diastolic blood pressure (DBP) 90–114 mmHg after 4 weeks’ single-blind placebo treatment were included in the study. Candesartan/ HCTZ 32/25mg combination therapy, candesartan 32mg monotherapy, HCTZ 25mg monotherapy, and placebo, allocated in a 5: 5: 5: 1 ratio, were administered once daily. The main outcome measure was adjusted (analysis of covariance) mean reductions in systolic blood pressure (SBP) and DBP.

Results: Mean reductions in SBP and DBP were significantly greater with candesartan/HCTZ 32/25mg (21/14 mmHg) than with candesartan 32mg (13/9 mmHg), HCTZ 25mg (12/8 mmHg) or placebo (4/3 mmHg) [p <0.001 for all comparisons]. The proportion of patients with controlled blood pressure (SBP <140 mmHg and DBP <90 mmHg) at the end of the study was also significantly greater in the candesartan/HCTZ 32/25mg group (63%) than in the other treatment groups (p <0.001 for all comparisons). All study treatments were generally well tolerated.

Conclusion: The antihypertensive effect of candesartan/HCTZ 32/25mg represents fully additive contributions from each of its components, and is generally well tolerated in patients with mild to moderate primary hypertension. This combination adds to the treatment options for improving blood pressure control in patients with hypertension.

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Acknowledgements

This study was funded and co-ordinated by AstraZeneca R&D with study management support from Quintiles. The sponsor was involved in the study design and the analysis of data. The International Co-ordinating Investigator, Prof. I. Edes, had access to study data and was responsible for data interpretation and the final manuscript. He has received fees from AstraZeneca for his role as study coordinator, but has no other conflicts of interests to declare. Professional medical writing support was funded by AstraZeneca and provided by Prof. D. Elmfeldt. The Multicentre Study Group gratefully acknowledges all efforts by investigators at study sites.

Members of the Multicentre Study Group

National co-ordinating investigators: Prof. I. Edes, Institute of Cardiology, Debrecen, Hungary (also served as the International Co-ordinating Investigator); Prof. L. Burgess, Tygerberg Hospital, W. Parow, South Africa; Dr A. Erglis, Clinical University Hospital, Riga, Latvia; Dr S. Heijmans, Linkebeek, Belgium; Dr J. Kasper, FNsP Bratislava, Bratislava, Slovakia; Dr S. Linntam, OY Mediteri Family Doctors, Tallinn, Estonia; Dr S. Stamate, Spitalul Clinic de Urgenta, Bucuresti, Romania; Prof. D. Zateyshchikov, Moscow City Hospital # 51, Moscow, Russian Federation.

AstraZeneca R&D Mölndal, Sweden: S. Andersson, M. Bjersing, D. Elmfeldt (retired), Y. Fox, B.W. Karlson, B. Olofsson and M. Ögren.

Quintiles Ltd, UK: I. Martin.

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  1. DEOEC Institute of Cardiology, Móricz Zsigmond u. 22, Debrecen 4032, Hungary

    Istvan Edes

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  1. Istvan Edes
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Correspondence to Istvan Edes.

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Edes, I. Combination Therapy with Candesartan Cilexetil 32mg and Hydrochlorothiazide 25mg Provides the Full Additive Antihypertensive Effect of the Components. Clin. Drug Investig. 29, 293–304 (2009). https://doi.org/10.2165/00044011-200929050-00002

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