Irbesartan and Atenolol in Hypertensive Heart Disease

NCT ID: NCT00389168

Last Updated: 2015-05-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

115 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-04-30

Study Completion Date

1997-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Irbesartan

Irbesartan per os titrated to 300 mg od, 48 weeks

Group Type EXPERIMENTAL

Irbesartan

Intervention Type DRUG

Titrated to 300 mg od, 48 weeks.

Atenolol

Atenolol per os titrated to 100 mg od, 48 weeks

Group Type ACTIVE_COMPARATOR

Atenolol

Intervention Type DRUG

Titrated to 100 mg od, 48 weeks.

Interventions

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Irbesartan

Titrated to 300 mg od, 48 weeks.

Intervention Type DRUG

Atenolol

Titrated to 100 mg od, 48 weeks.

Intervention Type DRUG

Other Intervention Names

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Aprovel Tenormin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role collaborator

Swedish Heart Lung Foundation

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role lead

Responsible Party

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Thomas Kahan

Professor, Principal investigator and Study Chair

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas Kahan, MD, PhD

Role: STUDY_CHAIR

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

Locations

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

Stockholm, , Sweden

Site Status

Countries

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Sweden

References

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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.

Reference Type RESULT
PMID: 11403367 (View on PubMed)

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.

Reference Type RESULT
PMID: 12172314 (View on PubMed)

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.

Reference Type RESULT
PMID: 12423712 (View on PubMed)

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.

Reference Type RESULT
PMID: 14639093 (View on PubMed)

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.

Reference Type RESULT
PMID: 16942935 (View on PubMed)

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.

Reference Type RESULT
PMID: 17444886 (View on PubMed)

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.

Reference Type RESULT
PMID: 17637792 (View on PubMed)

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.

Reference Type RESULT
PMID: 17762662 (View on PubMed)

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.

Reference Type RESULT
PMID: 18464745 (View on PubMed)

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.

Reference Type RESULT
PMID: 19486119 (View on PubMed)

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.

Reference Type RESULT
PMID: 14704728 (View on PubMed)

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.

Reference Type RESULT
PMID: 15716707 (View on PubMed)

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.

Reference Type RESULT
PMID: 24084214 (View on PubMed)

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.

Reference Type RESULT
PMID: 14700505 (View on PubMed)

Other Identifiers

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CV131-052

Identifier Type: -

Identifier Source: org_study_id

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