Chest Pain Drug Put to Test Against Arrhythmias
The drug ranolazine, approved to treat chest pain, is being tested as a potential treatment for ventricular arrhythmias, a condition for which there are limited treatment options for patients with heart disease.
The University of Rochester Medical Center is leading the new nationwide clinical trial, funded with a $10.5 million grant from the National Institutes of Health. It’s the first major study testing a new concept – blocking late sodium currents that govern key components of the electrical activity in the heart – to combat these deadly arrhythmias.
The approach represents a new avenue of therapy after two decades of no significant developments in innovative drug treatment of ventricular arrhythmias, say the principal investigators of the new study, Wojciech Zareba, M.D., Ph.D., and Arthur J. Moss, M.D., of the University of Rochester Medical Center, who are experts on the treatment of arrhythmias.
“This study is very important because current anti-arrhythmic agents do not offer enough protection for high-risk patients or can’t be used for long due to negative side effects, and some even cause additional heart rhythm disorders,” said Zareba, director of Clinical Cardiology Research and the Heart Research Follow-up Program. “We believe ranolazine is a promising therapy and that this trial could provide a revolutionary approach to treat these difficult heart rhythm disorders.”
In the double-blind, randomized clinical trial, high-risk patients who already have implantable cardioverter-defibrillators or ICDs will receive either ranolazine or placebo. The aim of the study, known as RAID, for Ranolazine in High-Risk Implantable Cardioverter-Defibrillator Patients, is to determine if ranolazine decreases death or cardiac arrhythmias, and also if it decreases the risk of hospitalizations from cardiac causes, including arrhythmias, heart failure or heart attack. Investigators plan to enroll approximately 1,440 patients at 80 centers across the United States.
According to Moss, “This is the right study at the right time. We know ranolazine has a good safety profile from its use to treat chest pain; early basic and clinical testing has been favorable; and we will be able to monitor precisely how patients respond to the drug by taking heart rhythm recordings directly from patients’ ICDs.” Moss will coordinate data management for the trial.
Ranolazine was tested previously in the high-profile MERLIN trial to determine if the drug reduced death rates in patients with acute coronary syndrome. While the drug was unsuccessful in reducing the risk of death in these patients, the study population was very large and researchers obtained significant data on various subgroups. They found that in people with coronary artery disease, ranolazine decreased the incidence of arrhythmias.
Ranolazine works by targeting the late sodium current that moves sodium ions into the heart muscle cells with each heartbeat, regulating the electrical activity of the heart. Damage to heart cells, such as from a heart attack, can cause excess sodium to leak into heart muscle cells. This extra, unwanted sodium puts patients at greater risk for arrhythmias and may prove to be an effective target for drugs such as ranolazine, blocking excessive inflow of sodium ions.
The trial, which is registered on clinicaltrials.gov (#NCT01215253), is funded by the National Heart, Lung and Blood Institute and will begin enrolling patients in spring 2011. Gilead Sciences, Inc., the biopharmaceutical company that markets ranolazine, will donate the study drug and placebo needed for the trial.