Pulse Reduction On Beta-blocker and Ivabradine Therapy
Status:
Recruiting
Trial end date:
2022-06-01
Target enrollment:
Participant gender:
Summary
Heart failure with reduced left ventricular ejection fraction (HFrEF) is the most common form
of chronic heart failure in subjects ≤ 75 years of age. Beta-blocker therapy greatly reduces
mortality and improves ventricular function in HFrEF patients, but 30-40% of patients do not
show improvement in ventricular function with beta blockade.
An extensive gene signaling network downstream from the beta1-adrenergic receptor, the
primary target of beta-blocker therapy is likely important for development and progression
HFrEF. Pathologic changes in this gene signaling network are only reversed towards normal
levels when ventricular function improves. One potential mechanism for failure to improve
ventricular function in HFrEF patients unresponsive to beta blocker therapy is a lack of
heart rate reduction.
Ivabradine is an FDA-approved medication believed to have therapeutic benefit in HFrEF
patients through reduction in heart rate independent of beta-blockade. Ivabradine has been
shown to reduce the risk of hospitalization for worsening HF in patients with stable,
symptomatic chronic heart failure with reduced EF (≤ 35%)in sinus rhythm with resting heart
rate ≥ 70 bpm and who are on maximally tolerated doses of beta blockers or who have a
contraindication to beta blockers.
Given the high rate of mortality and hospitalization of HFrEF patients even with current
therapies, there is a large unmet need for improving HFrEF therapy. The goals of this study
are to test the hypothesis that heart rate reduction is an important antecedent for
improvement in ventricular function, and to identify components of the beta1-adrenergic
receptor gene signaling network responsible for improvement in ventricular function caused by
heart rate reduction.
Phase:
Phase 4
Details
Lead Sponsor:
University of Colorado, Denver
Collaborators:
American Heart Association Ohio State University University of Utah