Heart rate in coronary artery disease: should we lower it?

OPINION STATEMENT: Elevated resting heart rate is an independent risk factor for cardiovascular morbidity and mortality in patients with and without coronary artery disease. In patients with known coronary artery disease, elevated heart rate reduces diastolic filling time and increases cardiac workload, resulting in supply demand mismatch with consequent ischemia and angina. While lower heart rate is associated with better prognosis, it is not known if pharmacological reduction in heart rate is beneficial and if heart rate is merely a marker for increased risk and worse outcomes. Certainly, physiologically lower resting heart rate as attained by exercise improves morbidity and mortality. While physiological reduction in heart rate is mainly a manifestation of increased parasympathetic drive, pharmacological reduction of heart rate with beta-blockers is mediated via the sympathetic pathway and associated with mixed outcomes. In addition, beta-blockers have other cardiovascular effects (lowering blood pressure), are metabolically active, and it is unknown if the beneficial effects (if any) are mediated via reduction in heart rate versus other cardiovascular effects. Ivabradine is a new medication that lowers heart rate selectively by inhibiting the I(f) current without other cardiovascular effects, offering for the first time a therapeutic agent that selectively targets heart rate. The medication has shown promise in early trials in patients with heart failure, but it is unclear if this agent will be beneficial in patients with stable coronary artery disease without heart failure.