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

NCT ID: NCT01554592

Last Updated: 2016-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2014-12-31

Brief Summary

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Statin withdrawal

Participants will received a placebo for 12 weeks.

Group Type: EXPERIMENTAL

Withdrawal of statin therapy

Intervention Type: DRUG

Participants currently received statin therapy will have their statin stopped for 12 weeks.

Stable statin therapy

Participants need to have been receiving statin therapy for at least 3 months and be on a stable dose.

Group Type: ACTIVE_COMPARATOR

Statin therapy

Intervention Type: DRUG

Participants will continue on stable statin therapy.

Interventions

Withdrawal of statin therapy

Participants currently received statin therapy will have their statin stopped for 12 weeks.

Intervention Type: DRUG

Statin therapy

Participants will continue on stable statin therapy.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Alfred

OTHER

Sponsor Role: lead

Responsible Party

Ingrid Hopper

Dr Ingrid Hopper

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Henry Krum, MBBS FRACP PhD

Role: PRINCIPAL_INVESTIGATOR

Alfred Hospital/Monash University

Locations

Clinical Pharmacology, Alfred Hospital

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

CP-02/12

Identifier Type: -

Identifier Source: org_study_id