Clinical Trial: The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure

Brief Summary:

To investigate whether the medicines eplerenone or atorvastatin have a favourable effect on diastolic heart failure.

Eplerenone is a drug that has been shown to be beneficial in Chronic Heart Failure due to pump failure. It can increase life expectancy and improve symptoms in these patients. It is not known whether or not eplerenone might be beneficial in heart failure with normal pump function (diastolic heart failure).

Atorvastatin is one of a group of cholesterol lowering medicines called statins, which have been shown to reduce cardiovascular disease in patients irrespective of whether cholesterol levels are high or normal. It is not known whether atorvastatin also reduces fibrosis of the heart which is one of the causes of diastolic heart failure.

Study hypothesis

  1. To investigate the impact of aldosterone antagonism or statin therapy on markers of collagen turnover in patients with diastolic heart failure.
  2. To assess the impact of aldosterone antagonism or statin therapy on markers of diastolic dysfunction and indices of clinical well being in patients with diastolic heart failure.

Detailed Summary:

Diastolic heart failure is a significant contributor to the heart failure syndrome. However, little work has been done on the causes of diastolic heart failure, and in contradistinction to those with systolic heart failure, little is know about the aetiology and therefore, there are few effective therapies.

It is generally believed that diastolic heart failure represents a problem with compliance and relaxation of the ventricle. One possible explanation for this is thought to be an abnormality of collagen structure in the myocardium. There are data from hypertensive populations as well as from hypertensive experimental models indicating an abnormal fibrotic process in patients with hypertensive heart disease. However, there are a few data on this potential aetiological explanation for diastolic heart failure.

It is now possible to measure serum markers of fibrosis in circulating blood. Work in this area has established the reproducibility and reliability of measurements of pro-collagen I and pro-collagen III amino-terminal, secreted as the collagen molecules are released from the fibroblast. These markers have been analysed in several settings, including normal individuals, hypertensive populations and in those with established heart failure due to systolic dysfunction. Recently we have completed a study on analysis of these factors in patients with proven diastolic heart failure. These data have demonstrated an increased activity of the amino terminal pro-collagen III (PIIINP) with a trend towards an increase in the amino-terminal pro-collagen I (PINP). Other relevant markers of the fibrotic process were not altered, including metalloproteinase enzymes (MMP) and tissue inhibitors of metalloproteinase enzymes (TIMP)

These observational data support the hypothesis that diast
Sponsor: St Vincent's University Hospital, Ireland

Current Primary Outcome: To investigate the impact of aldosterone antagonism or statin therapy on markers of collagen turnover in patients with diastolic heart failure. [ Time Frame: 12 months ]

Original Primary Outcome: To investigate the impact of aldosterone antagonism or statin therapy on markers of collagen turnover in patients with diastolic heart failure. [ Time Frame: 6 months ]

Current Secondary Outcome:

  • To assess the impact of aldosterone antagonism or statin therapy on markers of diastolic dysfunction by echocardiography [ Time Frame: 12 months ]
  • To assess the impact of aldosterone antagonism or statin therapy on indices of clinical well being [ Time Frame: 12 months ]
  • The assess the impact of aldosterone antagonism or statin therapy on diastolic indices by cardiac MRI [ Time Frame: 12 months ]


Original Secondary Outcome:

  • To assess the impact of aldosterone antagonism or statin therapy on markers of diastolic dysfunction [ Time Frame: 6 months ]
  • To assess the impact of aldosterone antagonism or statin therapy on indices of clinical well being [ Time Frame: 6 months ]


Information By: St Vincent's University Hospital, Ireland

Dates:
Date Received: July 19, 2007
Date Started: April 2006
Date Completion:
Last Updated: February 10, 2009
Last Verified: February 2009