Clinical Trial: If Channel Blockade With Ivabradine in Patients With Diastolic Heart Failure
Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional
Official Title: If Channel Blockade With Ivabradine in Patients With Diastolic Heart Failure
Brief Summary:
The purpose of this study is to investigate whether the medicine ivabradine, a novel drug which slows the heart rate has a favourable effect on patients with diastolic heart failure.
Ivabradine is a specific heart rate-lowering agent. It has a licence for treating patients with angina who are intolerant of agents such as beta blockers or whose angina is not adequately controlled. It has been shown to prolong exercise tolerance in these patients and to reduce the frequency of chest pain. Its mechanism of action is felt to be purely due to reducing heart rate, by as much as 10 beats per minute at rest, as well as by reducing the heart rate response to exercise.
Patients with diastolic heart failure often complain of breathlessness on exertion which relates to the stiffness or lack of compliance of their heart i.e. the heart fails to relax rapidly enough to allow it to fill with blood between each heart beat. This may result in high pressure in the heart chamber which backs up in to the lungs and may be experienced as breathlessness. There is little evidence that any specific therapy benefits patients with this type of heart failure besides treating coexisting problems such as high blood pressure or angina. By slowing the heart rate down with ivabradine, the heart would have a longer time to fill during exercise which would make it more effective. This slowing of the heart rate may therefore relieve the breathlessness experienced on activity such as walking to the shops or up a flight of stairs etc.
Detailed Summary:
Background:
Almost half of all patients with heart failure (HF) have preserved systolic function (PSHF) or heart failure with normal ejection fraction (HFNEF). Some of these have valvular abnormalities such as severe mitral or aortic regurgitation, severe anaemia, thyrotoxicosis or rarer tropical causes for heart failure. However, the majority of those with PSHF often have echocardiographic evidence of impaired diastolic function i.e. impaired relaxation and increased stiffness. This diastolic dysfunction may be related to age, hypertension or ischaemia. There is little evidence for any effective therapy in this large HF population despite randomised trials comparing placebo to ACE inhibitors i.e. perindopril in PEP-HF or angiotensin receptor blockers i.e. candesartan in the CHARM Preserved trial. There are also ongoing studies of aldosterone antagonists in diastolic heart failure i.e. eplerenone vs placebo in TOPCAT which continues to recruit.
In the absence of a strong evidence base, many physicians treat these patients with drugs that slow the heart rate, namely the calcium channel blocker verapamil and beta blockers. This has the effect of prolonging diastole or filling time and theoretically improving stroke volume thus reducing left ventricular end diastolic pressures (LVEDP) with resultant drop in wall stress and therefore less stimulus for myocardial fibrosis which exacerbates diastolic dysfunction by impeding compliance.
Hypothesis:
An alternative mechanism for slowing the heart rate is with ivabradine, a novel If channel blocker which acts purely on the sino atrial node with a mean heart rate lowering of 10 bpm in angina patients. This may result in improved diastolic filling which could be demonstrate by echocardi
Sponsor: St Vincent's University Hospital, Ireland
Current Primary Outcome: Improvement in echocardiographic indices of diastolic dysfunction [ Time Frame: 12 weeks ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Improvement in 6 minute walk test [ Time Frame: 12 weeks ]
- Patient global assessment [ Time Frame: 12 weeks ]
Original Secondary Outcome: Same as current
Information By: St Vincent's University Hospital, Ireland
Dates:
Date Received: September 19, 2008
Date Started: December 2012
Date Completion: January 2014
Last Updated: November 24, 2014
Last Verified: November 2014
