The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction

Denise Barnard, M.D., and her associates, are conducting a research study to find out more about ways to improve symptoms in patients with Heart Failure with Preserved Ejection Fraction (HFPEF). Heart failure with preserved ejection fraction is a condition where the heart squeezes well but is stiff. This stiffness in the heart muscle makes the heart unable to fill, leading to shortness of breath and decreased exercise tolerance. Subjects with HFPEF are asked to participate in this study. There will be approximately 40 participants enrolled in this study. The purpose of this study is to investigate the effects of Ranolazine (Ranexa) in patients with HFPEF. The study is sponsored by the manufacturers of the drug, Gilead Pharmaceuticals.

Ranolazine is a drug that affects the ion channels in the heart. In patients with heart failure, these ion channels do not work properly, and contribute to make the heart stiff. A stiff heart leads to the symptoms of shortness of breath which patients with HFPEF experience. Due to its properties, Ranolazine may improve this stiffness. Ranolazine could improve subject's shortness of breath and ability to exercise.

Currently, ranolazine carries FDA approval for the treatment of chronic angina only. We intend to study ranolazine in patients with HFPEF, in the absence of documented ischemia, to determine whether the drug's lusitropic properties can improve exercise capacity in HFPEF patients.

Previous trials of ranolazine in patients with chronic angina found that there was a dose-dependent relationship between improvements in exercise capacity and ranolazine. However, there did appear to be a plateau in which 1500 mg of ranolazine twice daily improved exercise capacity only slightly more than 1000 mg of ranolazine given twice daily. Additionally, there was a substantially higher rate of adverse events (mainly nausea, dizziness, and asthenia) with the higher dose. Given the desire to maximize benefit and minimize the risk of adverse events, ranolazine 1000 mg by mouth twice daily was chosen as the target dose.

To properly evaluate the effects of Ranolazine, this research study is set up as a double blind, placebo controlled study. Subjects will be randomly assigned (like rolling a dice) to either Ranolazine or placebo (inactive substance). Subjects will have a 50% chance of getting the study drug and 50% chance of getting placebo.