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Statin Therapy in Heart Failure: Potential Mechanisms of Benefit

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ClinicalTrials.gov Identifier: NCT00233480
Recruitment Status : Completed
First Posted : October 5, 2005
Results First Posted : March 20, 2020
Last Update Posted : March 20, 2020
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Tamara Horwich, University of California, Los Angeles

Brief Summary:
The goal of the investigators' study is to further understand the potentially beneficial effects of statin therapy in patients with heart failure. It is hypothesized that statins will 1) increase the heart's pumping ability 2) improve functioning of the sympathetic nervous system and 3) decrease immune activation in heart failure.

Condition or disease Intervention/treatment Phase
Heart Failure, Congestive Drug: atorvastatin Drug: placebo Phase 4

Detailed Description:

Recent evidence suggests that HMG-Coenzyme A (statin) therapy may be associated with improved survival in both ischemic and non-ischemic heart failure (HF). Large, randomized outcome studies of statins in HF are currently underway, but these trials will not address underlying mechanisms. The aim of the study is to investigate statins' potentially beneficial mechanisms of action in HF, focusing on: 1) sympathetic nervous system activation and 2) myocardial remodeling, and 3) immune activation in heart failure.

Fifty patients with systolic HF of non-ischemic etiology from a single center will be randomized in a double-blinded fashion to 3 months of atorvastatin 10mg QD (25 subjects) vs matching placebo QD (25 subjects). The following exams will be performed at baseline (pre-treatment) and at end of study (post-treatment): sympathetic microneurography, echocardiography, and peripheral blood chemokine analysis. Sympathetic microneurography at the peroneal nerve will directly quantify changes in sympathetic nerve activity (bursts/minute). Echocardiography (with the addition of MRI in a subset of subjects without pacemakers or implantable defibrillators) will be used to track changes in cardiac structure and function; indices of remodeling will include measurement of left ventricular mass index, left ventricular volume indices, left ventricular ejection fraction, and subendocardial scar quantification (MRI only). Immune activation will be characterized by circulating cytokines and chemokines. Additionally, quantification of established cardiac biomarkers (cardiac troponin, B-type natriuretic peptide, and C-reactive Protein), Holter monitor/heart rate variability studies, and quality of life and global clinical assessment will be performed pre- and post- treatment.

Neither sympathetic microneurography nor MRI have been previously utilized to assess statins' effects in humans with HF. The impact of statin therapy on inflammatory chemokine activation in HF also has not been studied. The knowledge gained from our proposed investigations may serve as a basis for understanding how statin therapy has potential to improve clinical outcomes in HF, and may ultimately lead to new therapeutic strategies for HF.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind Randomized, Placebo-Controlled, Single-Center Study to Assess the Impact of Statins on the Autonomic Nervous System and Cardiac Structure/Function in Non-Ischemic Heart Failure
Study Start Date : August 2005
Actual Primary Completion Date : February 2009
Actual Study Completion Date : February 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: active treatment
atorvastatin 10mg QD x 3 months
Drug: atorvastatin
atorvastatin 10mg PO QD
Other Name: lipitor

Placebo Comparator: placebo
matched placebo QD x 3 months
Drug: placebo
matched placebo Qd x 3 months

Primary Outcome Measures :
  1. LVEF (Left Ventricular Ejection Fraction) [ Time Frame: baseline and three months ]
    Left ventricular ejection fraction was assessed by transthoracic echocardiography according to Simpson's rule (biplane method of disks).

  2. Muscle Sympathetic Nerve Activity (by Sympathetic Microneurography) [ Time Frame: Baseline and three months ]

Secondary Outcome Measures :
  1. Left Ventricular End-diastolic Dimension (LVEDD) [ Time Frame: Baseline and three months ]
    The end-diastolic dimension of the left ventricle (in mm) was measured with 2D echocardiography performed by experienced technicians using Acuson Sequoia Echocardiography System

  2. Cardiac Biomarker Level BNP [ Time Frame: Baseline, 3 months ]
    B-type natriuretic peptide, measured pg/mL at baseline and post-treatment

  3. High-sensitivity C-reactive Protein (hsCRP) as a Cardiac Biomarker [ Time Frame: Baseline, Three months ]
  4. Cardiac Troponin I (cTnI) [ Time Frame: Baseline, Three months ]
    Participants with cTnI ≥0.04 ng/mL

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age≥18 years old
  • LVEF ≤ 35%, as documented by echocardiography, radionuclide ventriculography, gated SPECT, or contrast ventriculography within past 6 months
  • Symptomatic HF (NYHA II-IV) or current NYHA I with history of symptomatic HF within the last year
  • Stable doses of optimal HF medical therapy, unless documented contraindication.

Exclusion Criteria:

  • Ischemic etiology of HF, defined as the presence of at least one of the following four criteria; angiographic evidence of > 50% lesion in 1 or more of the 3 major epicardial vessels; history of myocardial infarction; history of revascularization procedure; evidence of significant perfusion defect in the setting of ischemic symptoms.
  • Clinical indication for statin treatment - coronary artery, cerebrovascular, or peripheral vascular disease
  • Major cardiovascular event or surgical procedure within past 8 weeks
  • LDL<70 mg/dL
  • HF secondary to congenital heart disease or uncorrected valvular disease
  • Treatment with statin within past 2 months
  • Pregnancy
  • Contraindication to statin: moderate liver disease, AST/ALT > 150 U/ L, known hypersensitivity
  • Likely to receive heart transplant within 3 months
  • Known peripheral or autonomic neuropathy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00233480

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United States, California
Ahmanson-UCLA Cardiomyopathy Center
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Tamara B Horwich, MD UCLA Division of Cardiology
Publications of Results:
PubMed ID 22041323

Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Tamara Horwich, Tamara Horwich, MD, MS, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00233480    
Other Study ID Numbers: UCLA IRB #04-12-007-01
1K23HL085097-01A1 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2005    Key Record Dates
Results First Posted: March 20, 2020
Last Update Posted: March 20, 2020
Last Verified: March 2020
Keywords provided by Tamara Horwich, University of California, Los Angeles:
Randomized Controlled Trial
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Sympathetic Nervous System
Ventricular Remodeling
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors