Irbesartan and Atenolol in Hypertensive Heart Disease

Condition(s) targeted: Hypertension

Intervention: Irbesartan vs atenolol (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Karolinska Institutet

Official(s) and/or principal investigator(s):
Thomas Kahan, MD, PhD, Study Chair, Affiliation: Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm, Sweden

The renin-angiotensin-aldosterone system has been implicated in the control of structural changes of the heart and the vasculature, beyond the effects on blood pressure.

This projects examines the importance of the renin-angiotensin-aldosterone system and the sympathetic nervous system in the control of cardiac and vascular structure and function in subjects with hypertension. Patients with hypertension and left ventricular hypertrophy were randomized to an angiotensin receptor blocker or a beta adrenergic receptor blocker for 48 w. Repeat investigations of blood pressure, structure and function of the heart and the vascular tree, and neurohormones were performed. Two control groups, consisting of normotensive subjects and of hypertensive subjects with no cardiac hypertrophy were also examined for comparison.

Official title: Randomized, Double-Blind Evaluation of the Effects of Irbesartan and Atenolol on Cardiovascular Structure and Function in Subjects With Hypertension and Left Ventricular Hypertrophy

Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Safety and tolerability of irbesartan compared to atenolol

Secondary outcome:

Compare changes in left ventricular mass

Evaluate changes in diastolic function

Compare changes in blood pressure

Examine the relationship between changes in left ventricular mass and sympathetic influence, and influence of the renin-angiotensin-aldosterone system

Compare the effects on carotid artery wall thickness

Detailed description: We included 115 patients with hypertension and cardiac hypertrophy, established by echocardiography. Extensive echocardiographic examinations, ultrasonography of the carotid arteries, 24h Holter registrations, 24h AMP monitoring, neurohormones and blood samples for inflammation and hemostasis markers and endothelial function were done at weeks 0, 12, 24, and 48. Matched control groups (1: 3, i. e. 38 normotensive subjects and 38 hypertensive subjects with no signs of hypertensive heart disease were examined at one occasion. All patients obtained irbesartan or atenolol for 12 weeks; a diuretic and a calcium antagonist was added when needed thereafter in order to obtained a blood pressure below 140/90 mm Hg. All analyses were performed central in a core laboratory.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- At least 18 ys old

- Male or female with no child bearing potential

- Seated blood pressure diastolic 90-115 mm Hg

- Left ventricular mass above 131 g/m2 for men, above 100 g/m2 for women

- Informed consent

Exclusion Criteria:

- Coronary artery disease, heart failure or other significant cardiac disorder

- Cerebrovascular accident within the past 6 months

- A seated systolic blood pressure above 200 mm Hg

- Significant renal disease, collagen or vascular disease, or gastrointestinal

condition

- Significant allergy or intolerance to study drug

- Alcohol or drug abuse

- Uncontrolled diabetes mellitus

Karolinska Institutet, Daprtment of Clinical Sciences, Danderyd Hospital, Cardiovascular Research Laboratory, Stockholm SE-182 88, Sweden

Starting date: April 1995
Ending date: April 1997
Last updated: October 17, 2006