Effects of Statin Therapy on Vascular Properties and Outcomes in Diastolic Heart Failure Patients

The study is designed to define the underlying vascular abnormalities present in patients with diastolic heart failure and test the effect of a therapy aimed at vascular abnormalities. This study is designed to investigate the effects of therapy with atorvastatin in subjects with diastolic heart failure to improve abnormalities of vascular and myocardial structure and function, with particular emphasis on arterial stiffness and endothelial dysfunction.

Study Overview

• Status: Terminated
• Conditions: Diastolic Heart Failure
• Intervention / Treatment: Other: placebo; Drug: Atorvastatin

Detailed Description

Forty subjects will be given either drug (atorvastatin 40 mg) or placebo in a randomized fashion once daily for six months. Using echocardiography, tonometry, and flow mediated dilation of conduit arteries and arterioles, baseline cardiovascular anatomy and physiology will be defined. Subjects that enroll in the study will be required to come in for 5 study visits. The initial visit is a screening visit; subject consent is obtained and an echocardiogram is performed as well as blood tests. At the randomization visit (4-14 days following screening), the subject will be provided with drug or placebo in a blinded fashion.Also at this visit, subjects will be asked to do a 6 minute walk, QOL questionnaire, and vascular function testing. There will be follow-up study visits at 1 and 3 months following randomization. At each follow-up visit a medical history, pill count and brief physical examination will be performed, a repeat QOL questionnaire administered, and blood tests to assess safety of the statin therapy. At 6 months, the final study visit will occur. At this visit a full history and detailed physical examination will be performed. Repeat echocardiogram, 6 minute walk test, QOL questionnaire, and vascular function examinations will be performed.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent,
• Age > 18,
• Ejection fraction ≥ 50%,
• hospitalization for heart failure in the last 6 months and
• current NYHA Class II-IV symptoms, OR

• current NYHA Class III-IV symptoms and one of the following:

  1. ECG or echocardiographic evidence of moderate/severe left ventricular hypertrophy,
  2. chest x-ray evidence of pulmonary congestion

Exclusion Criteria:

• Probable alternative cause of symptoms (pulmonary disease, severe anemia, etc.)
• Prior documented LVEF < 40% or qualitative moderate or greater LV systolic dysfunction.
• Current indication for statin therapy
• Intolerance to statin therapy.
• Documented ischemic heart disease requiring lipid-lowering therapy (i.e. CAD, myocardial infarction, stroke)
• Evidence of significant myocardial ischemia on stress testing at screening visit.
• Evidence of hepatic abnormality (defined as liver enzymes > 2 times the upper limit of normal values).
• Uncontrolled hypertension (BP > 150/100)
• Significant valvular disease.
• Atrial fibrillation
• Known familial hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy.
• Restrictive cardiomyopathy or systemic illness known to be associated with infiltrative heart disease (i.e. amyloidosis, sarcoidosis, hemochromatosis).
• Cor pulmonale or other cause of right heart failure not related to LV dysfunction.
• Clinically significant pulmonary disease.
• Pericardial constriction or hemodynamically significant pleural effusion.
• Uncontrolled arrhythmia.
• Any systemic condition other than heart failure that may limit survival to less than 2 years.
• Advance renal disease (serum creatinine > 3.0 mg/dl or on dialysis)
• Known intolerance or allergy to HMG CoA reductase inhibitors
• Uncontrolled hyper- or hypothyroidism.
• Any subject characteristic that may interfere with study compliance, such as baseline dementia, substance abuse, history of non-compliance with medications or appointments.
• Prisoners or other vulnerable populations.
• Any woman of child-bearing age with a documented positive pregnancy test.
• Subject is receiving therapy with other investigational therapy or is participating in any other clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Other: placebo; placebo; Drug: Atorvastatin; Atorvastatin - 40 mg orally daily for 6 months
Experimental: Atorvastatin; Heart failure patients assigned to atorvastatin	Drug: Atorvastatin; Atorvastatin - 40 mg orally daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Carotid-femoral Pulse Wave Velocity (CFPWV) in the Statin Treated vs. Control Group	6 months after initiation of intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite Cardiovascular Endpoint Incorporating Quality of Life (QOL) Assessment + Hospitalizations for Cardiovascular Disease and Mortality	6 months after initiation of intervention
Changes in Submaximal Exercise Capacity Measured by 6-minute Walk Test	6 months after initiation of intervention

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Nancy K Sweitzer, MD PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: January 2, 2008
• First Posted (Estimate): January 3, 2008

Study Record Updates

• Last Update Posted (Actual): March 26, 2019
• Last Update Submitted That Met QC Criteria: March 6, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Heart Failure, Congestive
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: H-2005-0430