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Candesartan Cilexetil/Hydrochlorothiazide Treatment in High-Risk Patients with Type 2 Diabetes Mellitus and Microalbuminuria

The CHILI T2D Study

Clinical Drug Investigation volume 30, pages 301–311 (2010)Cite this article

Abstract

Background: Arterial hypertension complicated by the presence of diabetes mellitus and microalbuminuria is a particularly hazardous risk-factor combination. Blockers of the renin-angiotensin system have been shown to be beneficial with respect to these risk factors in randomized clinical trials.

Objective: To provide proof of effectiveness for a fixed-dose combination such as candesartan cilexetil 16mg/hydrochlorothiazide (HCTZ) 12.5 mg in clinical practice within the context of a variety of concomitant diseases and medications.

Methods: CHILI T2D was a non-interventional, open-label, non-controlled, multicentre study in clinical practice that evaluated 4110 patients with type 2 diabetes, uncontrolled hypertension and microalbuminuria who were being prescribed a fixed-dose combination of candesartan cilexetil 16mg/HCTZ 12.5 mg (Biopress®). Documented outcomes included blood pressure (BP) reductions, metabolic changes, changes in albuminuria, and adverse events throughout the 12-week treatment period.

Results: Patients had a mean ±SD age of 64.0 ±10.3 years, 54.0% were male and the mean ±SD body mass index was 29.6 ±5.8 kg/m2. Coronary heart disease (34.3%), diabetic neuropathy (23.8%), retinopathy (18.6%) and heart failure (20.2%) were frequent co-morbidities. The use of candesartan cilexetil 16mg/HCTZ 12.5mg in patients with a mean ±SD baseline BP of 158.5±14.2/92.5 ±9.1 mmHg resulted in a substantial further reduction of office BP by a mean ±SD of −27.1 ±14.4/-13.1±9.5mmHg (p<0.001). The reduction was particularly pronounced in patients with severe hypertension (mean reduction of −44.7/−19.9 mmHg). Glucose (glycosylated haemoglobin [HbA1c], fasting blood glucose) as well as lipid parameters (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) were significantly improved (p< 0.001). Microalbuminuria, indicative of renal and cardiovascular risk, was significantly reduced by 28.8% (p< 0.001). Tolerability was excellent with only 16 out of 4110 patients experiencing any adverse event, of which six were considered to be serious.

Conclusions: The fixed-dose combination of candesartan cilexetil 16 mg/HCTZ 12.5 mg is highly effective in lowering blood pressure in type 2 diabetic patients with all stages of hypertension and microalbuminuria. The data indicate that low-dose HCTZ can safely be added to an existing drug regimen in this patient group to increase the BP-lowering effect, without compromising tolerability and the favourable metabolic profile of candesartan cilexetil monotherapy.

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Acknowledgements

This non-interventional study was conducted by Takeda Pharma GmbH, Aachen, Germany. We would like to thank the participating physicians, their assistants and all participating patients observed during the study. Our special gratitude goes to the Clinical Research Organization (CRO) factum-Gesellschaft für Statistik, wissenschaftliche Information und Kommunikation mbH, Offenbach, Germany, for data processing and conduction of the statistical analyses.

Reinhard Ketelhut designed the study and revised the manuscript for important intellectual content. Peter Bramlage explored the data, requested statistical analyses from the CRO (responsible statistician Michael Vornkahl) and wrote the first draft of the manuscript. Both authors reviewed and approved the final manuscript.

Reinhard Ketelhut has given lectures on behalf of Takeda. Peter Bramlage has acted as a consultant to, received honoraria from, and conducted research for Takeda.

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Authors and Affiliations

  1. Internal Medicine/Cardiology/Sports Medicine, Berlin, Germany

    Reinhard Ketelhut

  2. Institute for Cardiovascular Pharmacology and Epidemiology, Mahlow, Germany

    Peter Bramlage

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  1. Reinhard Ketelhut
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Correspondence to Reinhard Ketelhut.

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Ketelhut, R., Bramlage, P. Candesartan Cilexetil/Hydrochlorothiazide Treatment in High-Risk Patients with Type 2 Diabetes Mellitus and Microalbuminuria. Clin. Drug Investig. 30, 301–311 (2010). https://doi.org/10.1007/BF03256905

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Keywords

  • Blood Pressure Reduction
  • Candesartan
  • HCTZ
  • Thiazide Diuretic
  • Candesartan Cilexetil