Statin Therapy in Heart Failure: Potential Mechanisms of Benefit

March 6, 2020 updated by: Tamara Horwich, University of California, Los Angeles

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Ahmanson-UCLA Cardiomyopathy Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: active treatment
atorvastatin 10mg QD x 3 months
Drug: atorvastatin
atorvastatin 10mg PO QD
Other Names:
  • lipitor
Placebo Comparator: placebo
matched placebo QD x 3 months
Drug: placebo
matched placebo Qd x 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
baseline and three months
Muscle Sympathetic Nerve Activity (by Sympathetic Microneurography)
Time Frame: Baseline and three months
Baseline and three months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline and three months
Cardiac Biomarker Level BNP
Time Frame: Baseline, 3 months
B-type natriuretic peptide, measured pg/mL at baseline and post-treatment
Baseline, 3 months
High-sensitivity C-reactive Protein (hsCRP) as a Cardiac Biomarker
Time Frame: Baseline, Three months
Baseline, Three months
Cardiac Troponin I (cTnI)
Time Frame: Baseline, Three months
Participants with cTnI ≥0.04 ng/mL
Baseline, Three months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Pfizer

Investigators

  • Principal Investigator: Tamara B Horwich, MD, UCLA Division of Cardiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2005

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

October 4, 2005

First Submitted That Met QC Criteria

October 4, 2005

First Posted (Estimate)

October 5, 2005

Study Record Updates

Last Update Posted (Actual)

March 20, 2020

Last Update Submitted That Met QC Criteria

March 6, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCLA IRB #04-12-007-01
  • 1K23HL085097-01A1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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