Statin Therapy in Heart Failure: Potential Mechanisms of Benefit

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Tamara Horwich, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00233480
First received: October 4, 2005
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Heart Failure, Congestive
Drug: atorvastatin
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Left Ventricular Ejection Fraction (by echocardiography) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Muscle Sympathetic Nerve Activity (by sympathetic microneurography [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Circulating cytokine and chemokine levels, as well as cytokine and chemokine receptor expression [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Secondary indices of autonomic nervous system function: [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • echocardiography (all patients):LV mass, MPI, diastolic and systolic volume index, wall thickness [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • cardiac MRI (subgroup without pacemaker or ICD): LV mass, diastolic and systolic volume index, wall thickness, sphericity index, pulmonary arteriovenous transit time, cardiac output/index, regional wall motion, and subendocardial scar [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Established cardiac biomarkers: BNP, cTnI, hs-CRP [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Symptoms: NYHA class (assessed by blinded physician or nurse), QOL questionnaire [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Arrhythmia frequency on 24 hour Holter: ventricular ectopy, non-sustained ventricular tachycardia, sustained ventricular tachycardia, atrial fibrillation. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: August 2005
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00233480

Locations
United States, California
Ahmanson-UCLA Cardiomyopathy Center
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Pfizer
Investigators
Principal Investigator: Tamara B Horwich, MD UCLA Division of Cardiology
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tamara Horwich, Tamara Horwich, MD, MS, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00233480     History of Changes
Other Study ID Numbers: UCLA IRB #04-12-007-01, 1K23HL085097-01A1
Study First Received: October 4, 2005
Last Updated: March 29, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
Randomized Controlled Trial
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Sympathetic Nervous System
Ventricular Remodeling
Chemokines

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014