Polypharmacy in the Heart Failure Patient: Are All Prescribed Drug Classes Required? Statin Withdrawal Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by The Alfred
Sponsor:
Information provided by (Responsible Party):
Henry Krum, The Alfred
ClinicalTrials.gov Identifier:
NCT01554592
First received: March 8, 2012
Last updated: May 29, 2013
Last verified: May 2013
  Purpose

Heart failure (cardiomyopathy) is a chronic condition in which the heart fails to function as a pump to move blood around the body. This sets up a complex physiologic response to compensate, which include activation of many hormonal mechanisms which result in fluid accumulation.

In recent years, medications to block the hormonal response to heart failure are given as standard drugs, and these include ACE inhibitors and beta blockers. Mortality is reduced with these medications, as well as symptoms improved. Other medications are also used in heart failure, for which a clear-cut benefit has not been demonstrated. Statins, also called HMG CoA reductase inhibitors, are used to reduce cholesterol levels and can help to prevent heart failure by preventing heart attacks. They have been used in heart failure that is not caused by heart attacks in the belief that they had "pleiotropic" effects, meaning that they had beneficial effects in heart failure separate from the reduction in cholesterol.

However large trials in heart failure have demonstrated that statins do not increase survival compared with placebo. There is no evidence to recommend their routine use in established heart failure caused by either heart attacks or genetics.

The investigators propose that the use of statins in heart failure is unnecessary and could be stopped. The importance of finding evidence to cease unproven medications in heart failure cannot be understated. Patients with heart failure take an average of six prescription medications each day. Each medication has side effects and the interactions of all the drugs together are unknown. Statins are the commonest reason for side effects in patients with heart failure, causing muscle pains and gastrointestinal upset.

In this study, the investigators plan to withdraw statins from patients with stable heart failure in a closely monitored environment and watch for the effect of this on heart failure and on how they feel generally.


Condition Intervention
Heart Failure
Drug: Withdrawal of statin therapy
Drug: Statin therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Polypharmacy in the Heart Failure Patient: Are All Prescribed Drug Classes Required? Statin Withdrawal Study.

Resource links provided by NLM:


Further study details as provided by The Alfred:

Primary Outcome Measures:
  • NYHA (New York Heart Association) Heart Failure class [ Time Frame: baseline and after 12 weeks of treatemnt ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 6 minutes walk test [ Time Frame: Baseline and after 12 weeks of treatment ] [ Designated as safety issue: No ]
  • Quality of life questionnaire [ Time Frame: Baseline and after 12 weeks of treatment ] [ Designated as safety issue: No ]
  • Change in BNP (Brain natriuretic peptide) [ Time Frame: Baseline and after 12 weeks of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: March 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Statin withdrawal
Participants will received a placebo for 12 weeks.
Drug: Withdrawal of statin therapy
Participants currently received statin therapy will have their statin stopped for 12 weeks.
Active Comparator: Stable statin therapy
Participants need to have been receiving statin therapy for at least 3 months and be on a stable dose.
Drug: Statin therapy
Participants will continue on stable statin therapy.

  Eligibility

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

Inclusion Criteria:

  1. Over the age of 18 years
  2. Documented heart failure of ischaemic, idiopathic or hypertensive cause
  3. New York Heart Association (NYHA) class II, III or IV symptoms
  4. LVEF < 0.40, or no more than 0.35 if NYHA class II and ischaemic aetiology.
  5. Receiving ACE inhibitor or ARB (Angiotensin II Receptor Blockers), β-blocker and diuretic therapy at the optimal doses.
  6. Has been receiving statin therapy for at least 3 months
  7. Willing and able to provide informed consent

Exclusion Criteria:

  1. Treatment with statins primarily for treatment of hypercholesterolaemia
  2. Obstructive or restrictive cardiomyopathy
  3. Uncorrected primary valvular disease
  4. Active myocarditis
  5. Decompensated heart failure or a need for inotropic therapy
  6. Myocardial infarction within the past 6 months
  7. Unstable angina or stroke within the past 3 months
  8. PCI (Percutaneous coronary intervention), CABG (coronary artery bypass graft)or implantation of cardioverter-defibrillator or biventricular pacemaker within the past 3 months or a planned implantation of such a device
  9. Previous or planned cardiac transplantation
  10. Pericardial disease or systemic disease (eg amyloidosis)
  11. Acute or chronic liver disease
  12. Alanine and aspartate transminase concentrations more than 1.5 times the upper limit of normal
  13. Chronic muscle disease or an unexplained creatinine kinase level of more than 2.5 times the upper limit of normal
  14. Serum creatinine level greater than 221 micromol/L
  15. Previous treatment with cyclosporine
  16. Exercise capacity limited by factors other than cardiac dyspnoea
  17. Hospitalisation within one month of randomisation
  18. Pregnant or lactating women or women of childbearing potential who were not adequately protected against becoming pregnant
  19. Any other concurrent condition that, in the opinion of the investigator, would prevent completion of the clinical trial
  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: NCT01554592

Contacts
Contact: Henry Krum, MBBS, FRACP, PhD +61 3 9903 0042 henry.krum@monash.edu
Contact: Ingrid Hopper, MBBS, FRACP +61 3 9903 0569 i.hopper@alfred.org.au

Locations
Australia, Victoria
Clinical Pharmacology, Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Henry Krum, MBBS, FRACP, PhD    +61 3 9903 0042    henry.krum@monash.edu   
Contact: Ingrid Hopper, MBBS, FRACP    +61 3 9903 0569    i.hopper@alfred.org.au   
Principal Investigator: Henry Krum, MBBS, FRACP, PhD         
Sub-Investigator: Ingrid Hopper, MBBS, FRACP         
Sponsors and Collaborators
The Alfred
Investigators
Principal Investigator: Henry Krum, MBBS FRACP PhD Alfred Hospital/Monash University
  More Information

No publications provided

Responsible Party: Henry Krum, Prof Henry Krum, The Alfred
ClinicalTrials.gov Identifier: NCT01554592     History of Changes
Other Study ID Numbers: CP-02/12
Study First Received: March 8, 2012
Last Updated: May 29, 2013
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by The Alfred:
Heart Failure
Statin withdrawal

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

ClinicalTrials.gov processed this record on July 20, 2014