Heart Rate-lowering Drug Improves Exercise Capacity In Patients With Stable Angina

The study involved almost 900 patients from Canada and internationally with documented coronary artery disease and a history of stable angina. The objective was to determine if treatment with ivabradine could improve exercise capacity in these patients beyond what was previously achieved with standard treatments. Patients received either ivabradine 5 mg bid for two months (increased to 7.5 mg bid in 87.5 percent of patients for an additional two months) or placebo for four months in addition to their current beta blocker background therapy (atenolol 50 mg daily).

"Our findings confirm that adding ivabradine over and above the standard of care achieves increases exercise tolerance," said Dr. Jean-Claude Tardif, the study's lead investigator, a professor of medicine at the Université de Montréal and director of the Montreal Heart Institute Research Centre.

"For patients who have stable angina the results are very encouraging, particularly because of tolerability concerns with higher doses of beta blockers. As a result patients are often not achieving optimal heart rate reduction on standard therapy alone," adds Dr. Tardif.

An analysis of the data from treadmill exercise tests shows that patients who were treated with ivabradine in addition to a beta blocker (n=441) demonstrated a threefold improvement in total exercise duration at four months compared to those being treated with standard doses of beta blocker alone.

After four months of treatment, the ivabradine and beta blocker combination was associated with a mean heart rate reduction of nine beats per minute (bpm) compared to one bpm in patients remaining on beta blockers alone. Patients receiving the ivabradine and beta blocker combination also had considerable improvements in symptoms and ischemia as measured by time to limiting angina, time to angina onset, and time to 1-mm ST-segment depression.

Ivabradine is not yet available for clinical use in Canada.

About Coronary Artery Disease

Coronary artery disease (CAD) is the most common manifestation of cardiovascular disease. It refers to the hardening and shrinking of the coronary arteries (atherosclerosis) which leads to diminished blood flow and reduces oxygen supply to the heart muscle (ischemia). The lack of oxygen supply to the heart muscle may cause angina (heart pain). If the coronary artery becomes completely blocked, a whole section of the heart muscle is deprived of oxygen and dies, resulting in a myocardial infarction (MI) or heart attack. Coronary artery disease is a progressive silent disease that very often is unobserved until the first symptoms of ischemia or MI occur. Although the prognosis of patients with CAD has been greatly improved by advances in cardiovascular treatment, it is still the first cause of death.

Cardiovascular disease accounts for the death of more Canadians than any other disease. In fact, in Canada someone dies every seven minutes from it. According to the latest statistics available from Statistics Canada, in 2004 cardiovascular disease accounted for close to one third of all deaths in Canada (more than 72,000 deaths).

Heart rate and CAD

Heart rate is a major determinant of oxygen consumption and can precipitate most episodes of ischemia, both symptomatic and silent. Consequently, lowering the heart rate in patients with CAD reduces the heart's need for oxygen. A number of epidemiological studies have shown that heart rate is a strong and independent predictor of cardiovascular events in a wide range of patients, including those with CAD and post-myocardial infarction. This risk seems to become particularly evident with heart rate above 70 bpm.