The effective treatment of coronary artery disease targets two distinct goals, 
controlling symptomatic angina and decreasing the adverse events associated with 
ischemia. Traditional anti-anginal and anti-ischemic drugs function by altering 
the determinants of myocardial oxygen supply or demand, usually by altering 
loading conditions, changing the heart rate, or impacting contractility. 
Blockade of the late inward sodium current, late I(Na), offers another target 
for the treatment of ischemia. Blockade of late I(Na) reduces the sodium and 
calcium overload that follows ischemia. This improves myocardial relaxation and 
reduces left ventricular diastolic stiffness, in turn enhancing myocardial 
contractility and perfusion. Ranolazine, a late I(Na) inhibitor, has been shown 
to provide both anti-anginal and anti-ischemic benefits without significant 
alterations in the heart rate and blood pressure in patients with stable 
coronary artery disease. When evaluated in patients with acute coronary 
syndrome, ranolazine has been shown to decrease recurrent ischemia, but not 
significantly reduce the risk of death or myocardial infarction. This review 
will address the rationale that inhibition of the late sodium current is 
beneficial in reducing cardiac dysfunction during ischemia, and discuss the 
clinical studies supporting the use of ranolazine for its anti-anginal and 
anti-ischemic effects.