Statin Therapy in Heart Failure: Potential Mechanisms of Benefit
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00233480 |
|
Recruitment Status :
Completed
First Posted : October 5, 2005
Results First Posted : March 20, 2020
Last Update Posted : March 20, 2020
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Heart Failure, Congestive | Drug: atorvastatin Drug: placebo | Phase 4 |
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 (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 |
| 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 |
- 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).
- Muscle Sympathetic Nerve Activity (by Sympathetic Microneurography) [ Time Frame: Baseline and three months ]
- 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
- Cardiac Biomarker Level BNP [ Time Frame: Baseline, 3 months ]B-type natriuretic peptide, measured pg/mL at baseline and post-treatment
- High-sensitivity C-reactive Protein (hsCRP) as a Cardiac Biomarker [ Time Frame: Baseline, Three months ]
- Cardiac Troponin I (cTnI) [ Time Frame: Baseline, Three months ]Participants with cTnI ≥0.04 ng/mL
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, Learn About Clinical Studies.
| 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
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
| United States, California | |
| Ahmanson-UCLA Cardiomyopathy Center | |
| Los Angeles, California, United States, 90095 | |
| Principal Investigator: | Tamara B Horwich, MD | UCLA Division of Cardiology |
Other Publications:
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 |
| 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 |
|
Randomized Controlled Trial Hydroxymethylglutaryl-CoA Reductase Inhibitors Sympathetic Nervous System Ventricular Remodeling Chemokines |
|
Heart Failure Heart Diseases Cardiovascular Diseases Atorvastatin Anticholesteremic Agents Hypolipidemic Agents |
Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors |