New data show Atacand together with Zestril produces tighter blood pressure control in type 2 diabetes patients

December 07, 2000

The CALM study throws important light on the potential benefits of combining a long-acting AT1-receptor blocker with a long-acting ACE inhibitor in these patients

(London, UK, 8 December 2000) - The results of the CALM (Candesartan and Lisinopril Microalbuminuria) study published today in the British Medical Journal demonstrate that AT1-receptor blockade with Atacand® (candesartan cilexetil) together with ACE inhibition with Zestril® (lisinopril) is effective in reducing blood pressure and albumin excretion in hypertensive type 2 diabetic patients with microalbuminuria and that combination treatment is more effective than either drug used alone.1 This is the first study to have investigated dual blockade of the renin angiotensin system in hypertensive type 2 diabetes patients with microalbuminuria.

Lead investigator, Professor Carl Erik Mogensen, Professor of Medicine, University Hospital, Aarhus, Denmark, said: "The CALM study provides evidence for a potential role of dual blockade of the renin angiotensin system in type 2 diabetes patients in terms of its ability to lower blood pressure effectively, a beneficial effect on albuminuria and an excellent safety profile. The use of combined treatment is worthy of further investigation."

Professor Mogensen continued: "The international guidelines for blood pressure targets in diabetic subjects have emphasised the importance of aggressive blood pressure reduction.2 We also know that the majority of patients with diabetes and hypertension require treatment with more than one antihypertensive drug to achieve tight blood pressure control.3,4 The CALM study results show that a combination of the newer AT1-receptor blocking drug, candesartan cilexetil, and the established ACE inhibitor, lisinopril, is able to reduce blood pressure considerably more than monotherapy with either drug."

The CALM study was a randomised controlled trial involving 197 patients aged 30-75 years in four countries. Both Atacand® 16 mg once daily and Zestril® 20 mg once daily had significant and similar effects on both sitting and standing diastolic and systolic blood pressures after 12 and 24 weeks' treatment.

At 24 weeks the adjusted mean reductions in sitting diastolic blood pressures were 10.4 mmHg on Atacand® (p<0.001) and 10.7 mmHg on Zestril® (p<0.001). Sitting systolic blood pressure also fell significantly on both treatments, the reduction on Atacand® being 14.1 mmHg (p<0.001) and on Zestril® 16.7 mmHg (p<0.001).

Standing diastolic and systolic blood pressures were also markedly reduced and to a similar extent by the two drugs. Atacand® and Zestril® both reduced urinary albumin/creatinine ratio. At 24 weeks there was a 24% reduction in the group of patients treated with Atacand® and a 39% reduction in the Zestril® group. The difference between the drugs was not significant.

One third of the patients in the study were treated from weeks 12 to 24 with Atacand® 16 mg once daily and Zestril® 20 mg once daily given together. This regimen resulted in a greater fall in blood pressure than monotherapy with either drug with a mean reduction of 16.3 mmHg in sitting diastolic pressure (p<0.001) and 25.3 mmHg (p<0.001) in systolic pressure. Combined treatment also significantly reduced albumin/creatinine ratio.

All treatment regimens in the CALM study were generally well tolerated. The most common adverse events during any of the treatment regimens were respiratory infection, cough and headache which occurred in less than 10% of patients. Only 14 of 197 randomised patients stopped treatment due to adverse effects during the 24-week period. No marked changes in mean values for HbA1c or any routine laboratory variables were observed.
The CALM study was sponsored by AstraZeneca. Atacand® and Zestril® are marketed by AstraZeneca. Atacand® is manufactured under licence from Takeda Chemical Industries. AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of ethical (prescription) pharmaceuticals and the supply of healthcare services. It is one of the top five pharmaceutical companies in the world with healthcare sales of over $15 billion and leading positions in sales of gastrointestinal, oncology, anaesthesia including pain management, cardiovascular, central nervous system (CNS) and respiratory products.

For further information please contact:

Jean Kilshaw
Ketchum Alison MacKenzie
Tel: +44 20 7465 7050 Tel: +44 20 7465 8737
Fax: +44 20 7872 9679 Fax: +44 20 7872 9679

1. Mogensen CE et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria and non-insulin dependent diabetes: the candesartan and lisinopril (CALM) study. BMJ 2000; 321: 1440-1444
2. WHO Guidelines Subcommittee. 1999 World Health Organization - International Society of Hypertension guidelines for the management of hypertension. J Hypertens 1999; 17: 151-183
3. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 707-713
4. Hansson L, Zanchetti A, Carruthers SG et al for the HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351:1755-62.

Ketchum UK

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