The Effect of Lipitor on Aortic Stenosis - Full Text View

Sponsor:	The Cleveland Clinic
Collaborator:	Pfizer
Information provided by:	The Cleveland Clinic
ClinicalTrials.gov Identifier:	NCT00590135

Purpose

The purpose of this study is to find out if an approved medicine that is used to lower cholesterol called Lipitor can slow or stop progressive narrowing of the aortic heart valve in patients with a condition called aortic stenosis. Patients who have aortic stenosis who volunteer for this study will take Lipitor for 2 years and will undergo a brief exam by a physician, labwork to measure cholesterol, and a routine heart ultrasound (sound picture of the heart) at the start of the study and every 6 months, stopping at 2 years.

Condition	Intervention	Phase
Aortic Valve Stenosis	Drug: atorvastatin (Lipitor)	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Open Label, Historical Control, Single Group Assignment, Efficacy Study
Official Title:	The Effect of Statin Therapy (Atorvastatin) on the Progression of Calcific Valvular Aortic Stenosis

Resource links provided by NLM:

Drug Information available for: Atorvastatin Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:

Rate of change in the aortic valve area as measured by transthoracic echocardiography [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of change in the aortic valve area measured by transthoracic echocardiography compared to that of historical controls [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Rate of change in aortic valve area as measured by transthoracic echocardiography compared to standard of care group [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Change in the mean and peak gradients across the aortic valve as measured by transthoracic echocardiography in the treated group compared to historical control group. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	59
Study Start Date:	August 2000
Estimated Study Completion Date:	June 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
AS: Active Comparator Patients with mild to moderate calcific aortic stenosis	Drug: atorvastatin (Lipitor) atorvastatin 40 mg by mouth once daily

Detailed Description:

This is a prospective, single-center study assessing the effect of atorvastatin 40 mg/day (Lipitor, Pfizer) on the progression of calcific aortic stenosis in approximately 70 patients with mild to moderate calcific AS of a tricuspid or bicuspid aortic valve. As a control population, published data on historical AS cohorts will be used, employing the accepted rate of progression of a decrease in aortic valve area of 0.1 cm²/year. Additionally, also for comparison, we will prospectively study a registry of AS patients who meet our entry criteria but are either currently already being treated with or refuse to take an HMG-CoA reductase inhibitor (referred to as the "standard care" group).

All patient visits, laboratory studies, and echocardiograms will be performed at the Cleveland Clinic Foundation in Cleveland, Ohio with the exception of the 12-week visit ALT measurement which may be done at the patient's local doctor's office and the results faxed to Imaging Research. The 12-week follow-up assessment may be completed over the phone to establish any change in patient status since baseline, study medication compliance, concomitant medication use and to ascertain whether or not the appropriate laboratory test was obtained. Over a 2-year period, assessments will be conducted at baseline, 6, 12, 18, and 24 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Mild to moderate calcific AS of a tricuspid or bicuspid aortic valve
Echocardiographic derived mean pressure gradient >10 mmHg and an aortic valve area of 0.9 to 1.7 cm2 by continuity equation.
Laboratory evidence of LDL-c>70 mg/dl within 12 months prior to recruitment.

Exclusion Criteria:

Left ventricular ejection fraction <50%
Valvular area of 0.9 cm2 and a mean gradient >30 mmHg
Rheumatic heart disease
>Moderate (2+) aortic insufficiency
Prior statin therapy to include: >10 mg of atorvastatin (Lipitor) or >20 mg of other HMG-CoA Reductase Inhibitors (statins)
End-stage renal disease (ESRD)
History of thoracic radiation
Unable or unwilling to sign informed consent
Unable to unwilling to return for follow-up
Other clinically important renal, pulmonary, hepatic, neurological, endocrine, or hematological disorders, vasculitis, or any other situation or medical condition that, in the investigator's opinion, would make survival for the duration of the study unlikely, or would otherwise interfere with optimal participation in the study or produce a significant risk to the patient
Severe pulmonary hypertension (>55 mmHg)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00590135

Locations

United States, Ohio
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

The Cleveland Clinic

Pfizer

Investigators

Principal Investigator:

Brian P Griffin, M.D.

The Cleveland Clinic

More Information

Publications:

Passik CS, Ackermann DM, Pluth JR, Edwards WD. Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases. Mayo Clin Proc. 1987 Feb;62(2):119-23.

Walton KW, Williamson N, Johnson AG. The pathogenesis of atherosclerosis of the mitral and aortic valves. J Pathol. 1970 Jul;101(3):205-20. No abstract available.

Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O'Brien KD. Characterization of the early lesion of 'degenerative' valvular aortic stenosis. Histological and immunohistochemical studies. Circulation. 1994 Aug;90(2):844-53.

Kawaguchi A, Miyatake K, Yutani C, Beppu S, Tsushima M, Yamamura T, Yamamoto A. Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia. Am Heart J. 1999 Mar;137(3):410-8.

O'Brien KD, Reichenbach DD, Marcovina SM, Kuusisto J, Alpers CE, Otto CM. Apolipoproteins B, (a), and E accumulate in the morphologically early lesion of 'degenerative' valvular aortic stenosis. Arterioscler Thromb Vasc Biol. 1996 Apr;16(4):523-32.

Chan KL, Ghani M, Woodend K, Burwash IG. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve. Am J Cardiol. 2001 Sep 15;88(6):690-3. No abstract available.

Hofmann T, Kasper W, Meinertz T, Spillner G, Schlosser V, Just H. Determination of aortic valve orifice area in aortic valve stenosis by two-dimensional transesophageal echocardiography. Am J Cardiol. 1987 Feb 1;59(4):330-5.

Stoddard MF, Arce J, Liddell NE, Peters G, Dillon S, Kupersmith J. Two-dimensional transesophageal echocardiographic determination of aortic valve area in adults with aortic stenosis. Am Heart J. 1991 Nov;122(5):1415-22.

Otto CM, Pearlman AS, Gardner CL. Hemodynamic progression of aortic stenosis in adults assessed by Doppler echocardiography. J Am Coll Cardiol. 1989 Mar 1;13(3):545-50.

Roger VL, Tajik AJ, Bailey KR, Oh JK, Taylor CL, Seward JB. Progression of aortic stenosis in adults: new appraisal using Doppler echocardiography. Am Heart J. 1990 Feb;119(2 Pt 1):331-8.

Faggiano P, Ghizzoni G, Sorgato A, Sabatini T, Simoncelli U, Gardini A, Rusconi C. Rate of progression of valvular aortic stenosis in adults. Am J Cardiol. 1992 Jul 15;70(2):229-33.

Peter M, Hoffmann A, Parker C, Lüscher T, Burckhardt D. Progression of aortic stenosis. Role of age and concomitant coronary artery disease. Chest. 1993 Jun;103(6):1715-9.

Responsible Party:	The Cleveland Clinic Foundation ( Brian P. Griffin, M.D. )
Study ID Numbers:	IRB 3516
Study First Received:	December 26, 2007
Last Updated:	January 9, 2008
ClinicalTrials.gov Identifier:	NCT00590135 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by The Cleveland Clinic:

calcific aortic valve stenosis
echocardiography, transthoracic

Additional relevant MeSH terms:

Pathological Conditions, Anatomical
Antimetabolites
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Enzyme Inhibitors
Constriction, Pathologic
Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Heart Valve Diseases
Therapeutic Uses
Cardiovascular Diseases
Aortic Valve Stenosis
Atorvastatin
Ventricular Outflow Obstruction

ClinicalTrials.gov processed this record on February 08, 2010