Irbesartan and Atenolol in Hypertensive Heart Disease

Hypertension Clinical Trial

— SILVHIA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00389168
• Other study ID #: CV131-052
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 17, 2006
• Last updated: May 3, 2015
• Start date: April 1995
• Est. completion date: April 1997

Study information

• Verified date: May 2015
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial Summary

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 weeks. 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.

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 ambulatory blood pressure monitoring 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: April 1997
• Est. primary completion date: April 1997
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Irbesartan
Titrated to 300 mg od, 48 weeks.
• Atenolol
Titrated to 100 mg od, 48 weeks.

Locations

Country	Name	City	State
Sweden	Karolinska Institutet, Daprtment of Clinical Sciences, Danderyd Hospital, Cardiovascular Research Laboratory	Stockholm

Sponsors (4)

Lead Sponsor	Collaborator
Karolinska Institutet	Bristol-Myers Squibb, Sanofi, Swedish Heart Lung Foundation

Country where clinical trial is conducted

Sweden, 

References & Publications (14)

Jekell A, Malmqvist K, Wallén NH, Mörtsell D, Kahan T. Markers of inflammation, endothelial activation, and arterial stiffness in hypertensive heart disease and the effects of treatment: results from the SILVHIA study. J Cardiovasc Pharmacol. 2013 Dec;62( — View Citation

Kurland L, Hallberg P, Melhus H, Liljedahl U, Hashemi N, Syvänen AC, Lind L, Kahan T. The relationship between the plasma concentration of irbesartan and the antihypertensive response is disclosed by an angiotensin II type 1 receptor polymorphism: results — View Citation

Kurland L, Liljedahl U, Karlsson J, Kahan T, Malmqvist K, Melhus H, Syvänen AC, Lind L. Angiotensinogen gene polymorphisms: relationship to blood pressure response to antihypertensive treatment. Results from the Swedish Irbesartan Left Ventricular Hypertr — View Citation

Liljedahl S, Kahan T, Lind L, Arnlöv J. The effects of antihypertensive treatment on the doppler-derived myocardial performance index in patients with hypertensive left ventricular hypertrophy: results from the Swedish irbesartan in left ventricular hyper — View Citation

Malmqvist K, Kahan T, Edner M, Bergfeldt L. Cardiac repolarization and its relation to ventricular geometry and rate in reverse remodelling during antihypertensive therapy with irbesartan or atenolol: results from the SILVHIA study. J Hum Hypertens. 2007 — View Citation

Malmqvist K, Kahan T, Edner M, Bergfeldt L. Comparison of actions of irbesartan versus atenolol on cardiac repolarization in hypertensive left ventricular hypertrophy: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation Versus A — View Citation

Malmqvist K, Kahan T, Edner M, Held C, Hägg A, Lind L, Müller-Brunotte R, Nyström F, Ohman KP, Osbakken MD, Ostergern J. Regression of left ventricular hypertrophy in human hypertension with irbesartan. J Hypertens. 2001 Jun;19(6):1167-76. — View Citation

Malmqvist K, Ohman KP, Lind L, Nyström F, Kahan T. Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone system in human primary hypertension: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (S — View Citation

Mörtsell D, Malmqvist K, Held C, Kahan T. Irbesartan reduces common carotid artery intima-media thickness in hypertensive patients when compared with atenolol: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) stu — View Citation

Müller-Brunotte R, Edner M, Malmqvist K, Kahan T. Irbesartan and atenolol improve diastolic function in patients with hypertensive left ventricular hypertrophy. J Hypertens. 2005 Mar;23(3):633-40. — View Citation

Müller-Brunotte R, Kahan T, López B, Edner M, González A, Díez J, Malmqvist K. Myocardial fibrosis and diastolic dysfunction in patients with hypertension: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SIL — View Citation

Müller-Brunotte R, Kahan T, Malmqvist K, Edner M; Swedish ibesartan left ventricular hypertrophy investigation vs atenolol (SILVHIA). Blood pressure and left ventricular geometric pattern determine diastolic function in hypertensive myocardial hypertrophy — View Citation

Müller-Brunotte R, Kahan T, Malmqvist K, Ring M, Edner M. Tissue velocity echocardiography shows early improvement in diastolic function with irbesartan and atenolol therapy in patients with hypertensive left ventricular hypertrophy. Results form the Swed — View Citation

Nyström F, Malmqvist K, Ohman KP, Kahan T. Nurse-recorded and ambulatory blood pressure predicts treatment-induced reduction of left ventricular hypertrophy equally well in hypertension: results from the Swedish irbesartan left ventricular hypertrophy inv — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Left Ventricular Mass Index	Repeated measures multivariate analysis of variance (MANOVA) at time points 0, 12, 24, and 48 weeks. Data are presented as left ventricular mass in gram (g) indexed for body mass index (in m^2).	Baseline and 48 weeks	No
Secondary	Number of Participants With Serious Adverse Events	Safety was assessed by non-directed questions, and all observed and volunteered adverse events were recorded at each study visit. Serious adverse events were defined by, and reported according to the regulations of good clinical practice (GCP). none were considered related to the study medication.	Treatment period was baseline to 48 weeks	No
Secondary	Left Ventricular Diastolic Function Assessed by the E/A Ratio	Changes in left ventricular diastolic function from baseline to week 48 will be evaluated as the difference in E/A ratio. Conventional pulsed wave Doppler echocardiography was used for recordings of mitral inflow in. The peak of early (E) and late (A) mitral flow velocities were measured, and the E/A-ratio was calculated. Repeated measures MANOVA at time points 0, 12, 24, and 48 weeks. Some echocardiographic recordings at some time point may be of insufficient quality or missing, and the number of observations may not always correspond to the total number of participants at all time points.	Baseline to 48 weeks	No
Secondary	Blood Pressure	Difference in Diastolic Blood Pressure. Repeated measures multivariable analysis of variance (MANOVA) at time points 0, 12, 24, and 48 weeks	Baseline to 48 weeks	No
Secondary	Changes of Venous Plasma Angiotensin II as a Marker of the Renin-Angiotensin-Aldosterone System	Venous plasma concentrations of angiotensin II were measured in order to study the possible associations between the activity of the renin-angiotensin-aldosteone system and changes in left ventricular mass. Further analyses of other components of the renin-angiotensin-aldosterone system and of other hormonal system (e.g. the sympathetic nervous system) have also been performed and published. Repeated measures MANOVA at time points 0, 12, 24, and 48 weeks. Data were log-transformed to avoid skewness before statistical evaluation. However, tabular data are given as mean values with 95% confidence to improve readability.	Baseline to 48 weeks	No
Secondary	Effects on Carotid Artery Wall Thickness	Changes in common carotid artery intima-media thickness, assessed by ultrasonography.	Baseline to 48 weeks	No