Statin Therapy in Heart Failure: Potential Mechanisms of Benefit

NCT00233480 | Completed Phase 4 Results DMC

• 2 other identifiers: UCLA IRB #04-12-007-011K23HL085097-01A1
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure, Congestive

Keywords

Randomized Controlled Trial; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Sympathetic Nervous System; Ventricular Remodeling; Chemokines

Outcome Measures

Primary Outcomes (2)

• LVEF (Left Ventricular Ejection Fraction)

  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)

  Baseline and three months

Secondary Outcomes (4)

• Left Ventricular End-diastolic Dimension (LVEDD)

  Baseline and three months

• Cardiac Biomarker Level BNP

  Baseline, 3 months

• High-sensitivity C-reactive Protein (hsCRP) as a Cardiac Biomarker

  Baseline, Three months

• Cardiac Troponin I (cTnI)

  Baseline, Three months

Study Arms (2)

active treatment

EXPERIMENTAL

atorvastatin 10mg QD x 3 months

Drug: atorvastatin

placebo

PLACEBO COMPARATOR

matched placebo QD x 3 months

Drug: placebo

Interventions

atorvastatin DRUG

atorvastatin 10mg PO QD

Also known as: lipitor

active treatment

placebo DRUG

matched placebo Qd x 3 months

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Pfizer: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Ahmanson-UCLA Cardiomyopathy Center

Los Angeles, California, 90095, United States

Location

Related Publications (4)

• Horwich TB, Middlekauff HR. Potential autonomic nervous system effects of statins in heart failure. Heart Fail Clin. 2008 Apr;4(2):163-70. doi: 10.1016/j.hfc.2008.01.004.

  PMID: 18433696 BACKGROUND

• Horwich TB, MacLellan WR. Atorvastatin and statins in the treatment of heart failure. Expert Opin Pharmacother. 2007 Dec;8(17):3061-8. doi: 10.1517/14656566.8.17.3061.

  PMID: 18001265 BACKGROUND

• PubMed ID 22041323

  RESULT

• Horwich TB, Middlekauff HR, Maclellan WR, Fonarow GC. Statins do not significantly affect muscle sympathetic nerve activity in humans with nonischemic heart failure: a double-blind placebo-controlled trial. J Card Fail. 2011 Nov;17(11):879-86. doi: 10.1016/j.cardfail.2011.07.008. Epub 2011 Sep 3.

  PMID: 22041323 DERIVED

MeSH Terms

Conditions

Heart Failure; Ventricular Remodeling

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Tamara B Horwich, MD
• Organization: Ahmanson-UCLA Cardiomyopathy Center

thorwich@mednet.ucla.edu

310-825-8676

Study Officials

• Tamara B Horwich, MD

  UCLA Division of Cardiology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Tamara Horwich, MD, MS

Study Record Dates

• First Submitted: October 4, 2005
• First Posted: October 5, 2005
• Study Start: August 1, 2005
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: March 20, 2020
• Results First Posted: March 20, 2020

Record last verified: 2020-03

Locations

US (1)