Novel therapeutic approaches to treating chronic angina in the setting of chronic ischemic heart disease.

Pharmacologic therapy to alleviate symptoms in chronic angina has been enhanced by the recent approval of several novel compounds that complement the traditional approach using beta-adrenergic blocking drugs, calcium antagonists, and long-acting nitrates. In the United States, ranolazine, a drug that inhibits late I(Na), was approved for patients with chronic angina that remain symptomatic on beta-blockers, calcium antagonists, or long-acting nitrates, on the basis of an acceptable safety profile and efficacy in several randomized placebo controlled studies. A slight increase in the QT interval is observed (<10 ms on average) at the maximum approved dose of 1,000 mg twice daily. Therefore, an ECG should be acquired at baseline and during follow-up, and the drug should not be used in patients with QT prolongation or those who are on QT prolonging drugs unless longer term randomized outcome data demonstrates no excess risk. The MERLIN trial of non-ST-elevation acute coronary syndrome (NSTE ACS) randomized 6,560 patients to assess the potential benefit of ranolazine in reducing the composite endpoint of cardiovascular death, myocardial infarction, and recurrent ischemia, with results expected in 2007. In Europe, ivabradine, a drug that inhibits the hyperpolarization-activated mixed sodium/potassium inward I(f) current, which slows the rest and exercise heart rate, was approved in 2005. Ivabradine at a dose of 10 mg twice daily has been shown to have similar efficacy to amlodipine 10 mg once daily or atenolol 100 mg once daily in alleviating chronic angina symptoms. In this review, several other novel investigational approaches are presented and patient selection considerations for the most recent approved drugs for chronic angina are discussed.