Irbesartan and Atenolol in Hypertensive Heart Disease

NCT00389168 | Completed Phase 2 Results

• 1 other identifier: CV131-052
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypertension

Keywords

Hypertension; Cardiac hypertrophy; Angiotensin; Human

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Number of Participants With Serious Adverse Events

  Treatment period was baseline to 48 weeks

• Left Ventricular Diastolic Function Assessed by the E/A Ratio

  Baseline to 48 weeks

• Blood Pressure

  Baseline to 48 weeks

• Changes of Venous Plasma Angiotensin II as a Marker of the Renin-Angiotensin-Aldosterone System

  Baseline to 48 weeks

• Effects on Carotid Artery Wall Thickness

  Baseline to 48 weeks

Study Arms (2)

Irbesartan

EXPERIMENTAL

Irbesartan per os titrated to 300 mg od, 48 weeks

Drug: Irbesartan

Atenolol

ACTIVE COMPARATOR

Atenolol per os titrated to 100 mg od, 48 weeks

Drug: Atenolol

Interventions

Irbesartan DRUG

Titrated to 300 mg od, 48 weeks.

Also known as: Aprovel

Irbesartan

Atenolol DRUG

Titrated to 100 mg od, 48 weeks.

Also known as: Tenormin

Atenolol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Bristol-Myers Squibb: collaborator
• Sanofi: collaborator
• Swedish Heart Lung Foundation: collaborator

Study Sites (1)

Karolinska Institutet, Daprtment of Clinical Sciences, Danderyd Hospital, Cardiovascular Research Laboratory

Stockholm, SE-182 88, Sweden

Location

Related Publications (14)

• Malmqvist K, Kahan T, Edner M, Held C, Hagg A, Lind L, Muller-Brunotte R, Nystrom 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. doi: 10.1097/00004872-200106000-00023.

  PMID: 11403367 RESULT

• Nystrom 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 investigation versus atenolol (SILVHIA) study. J Hypertens. 2002 Aug;20(8):1527-33. doi: 10.1097/00004872-200208000-00015.

  PMID: 12172314 RESULT

• 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 Atenolol (SILVHIA). Am J Cardiol. 2002 Nov 15;90(10):1107-12. doi: 10.1016/s0002-9149(02)02777-7.

  PMID: 12423712 RESULT

• Malmqvist K, Ohman KP, Lind L, Nystrom 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 (SILVHIA). J Cardiovasc Pharmacol. 2003 Dec;42(6):719-26. doi: 10.1097/00005344-200312000-00005.

  PMID: 14639093 RESULT

• Muller-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 Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA). Am J Hypertens. 2006 Sep;19(9):927-36. doi: 10.1016/j.amjhyper.2006.02.009.

  PMID: 16942935 RESULT

• Mortsell 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) study. J Intern Med. 2007 May;261(5):472-9. doi: 10.1111/j.1365-2796.2007.01775.x.

  PMID: 17444886 RESULT

• 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 Dec;21(12):956-65. doi: 10.1038/sj.jhh.1002250. Epub 2007 Jul 19.

  PMID: 17637792 RESULT

• Muller-Brunotte R, Kahan T, Lopez B, Edner M, Gonzalez A, Diez J, Malmqvist K. Myocardial fibrosis and diastolic dysfunction in patients with hypertension: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). J Hypertens. 2007 Sep;25(9):1958-66. doi: 10.1097/HJH.0b013e3282170ada.

  PMID: 17762662 RESULT

• Kurland L, Hallberg P, Melhus H, Liljedahl U, Hashemi N, Syvanen 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 from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) Trial. Am J Hypertens. 2008 Jul;21(7):836-9. doi: 10.1038/ajh.2008.190. Epub 2008 May 8.

  PMID: 18464745 RESULT

• Liljedahl S, Kahan T, Lind L, Arnlov 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 hypertrophy investigation versus atenolol (SILVHIA). Echocardiography. 2009 Aug;26(7):753-8. doi: 10.1111/j.1540-8175.2008.00886.x.

  PMID: 19486119 RESULT

• Muller-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. J Hum Hypertens. 2003 Dec;17(12):841-9. doi: 10.1038/sj.jhh.1001622.

  PMID: 14704728 RESULT

• Muller-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. doi: 10.1097/01.hjh.0000160222.17092.b8.

  PMID: 15716707 RESULT

• Jekell A, Malmqvist K, Wallen NH, Mortsell 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(6):559-66. doi: 10.1097/FJC.0000000000000017.

  PMID: 24084214 RESULT

• Kurland L, Liljedahl U, Karlsson J, Kahan T, Malmqvist K, Melhus H, Syvanen AC, Lind L. Angiotensinogen gene polymorphisms: relationship to blood pressure response to antihypertensive treatment. Results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. Am J Hypertens. 2004 Jan;17(1):8-13. doi: 10.1016/j.amjhyper.2003.09.009.

  PMID: 14700505 RESULT

MeSH Terms

Conditions

Hypertension; Cardiomegaly

Interventions

Irbesartan; Atenolol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Spiro Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines

Results Point of Contact

• Title: Thomas Kahan, MD
• Organization: Karolinska Institutet, Stockholm, Sweden

thomas.kahan@ds.se

+46 8 123 568 61

Study Officials

• Thomas Kahan, MD, PhD

  Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm, Sweden

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Principal investigator and Study Chair

Study Record Dates

• First Submitted: October 17, 2006
• First Posted: October 18, 2006
• Study Start: April 1, 1995
• Primary Completion: April 1, 1997
• Study Completion: April 1, 1997
• Last Updated: May 5, 2015
• Results First Posted: May 5, 2015

Record last verified: 2015-05

Locations

SE (1)