Safety and Efficacy of Ranolazine for the Treatment of Chronic Angina Pectoris

Abstract

Coronary heart disease is a global malady and it is the leading cause of death in the United States. Chronic stable angina is the most common manifestation of coronary heart disease and it results from the imbalance between myocardial oxygen supply and demand due to reduction in coronary blood flow. Therefore, in addition to lifestyle changes, commonly used pharmaceutical treatments for angina (nitrates, β-blockers, Ca²⁺ channel blockers) are aimed at increasing blood flow or decreasing O₂ demand. However, patients may continue to experience symptoms of angina. Ranolazine is a relatively new drug with anti-anginal and anti-arrhythmic effects. Its anti-anginal mechanism is not clearly understood but the general consensus is that ranolazine brings about its anti-anginal effects by inhibiting the late Na⁺ current and the subsequent intracellular Ca²⁺ accumulation. Recent studies suggest other effects of ranolazine that may explain its anti-anginal and anti-arrhythmic effects. Nonetheless, clinical trials have proven the efficacy of ranolazine in treating chronic angina. It has been shown to be ineffective, however, in treating acute coronary syndrome patients. Ranolazine is a safe drug with minimal side effects. It is metabolized mainly in the liver and cleared by the kidney. Therefore, caution must be taken in patients with impaired hepatic or renal function. Due to its efficacy and safety, ranolazine was approved for the treatment of chronic angina by the Food and Drug Administration (FDA) in 2006.

Keywords: chronic angina; late Na+ current; mitochondria; ranolazine.

Figure 1

Summary of the effects of three doses of ranolazine on exercise treadmill test parameters. Notes: values shown represent difference from placebo in seconds. Data are mean ± standard error. *P < 0.05 in treatment with ranolazine vs. placebo. b.i.d. = twice daily.

Figure 2

Summary of the effects of two doses of ranolazine on exercise treadmill test parameters. Notes: values shown represent difference from baseline values in seconds. placebo indicates treatment only with another anti-anginal drug (atenolol 50 mg, amlodipine 5 mg, diltiazem 180 mg). Data are mean ± standard error. *P < 0.05 in treatment with ranolazine vs. placebo. b.i.d. = twice daily.

Figure 3

Summary of the effects of two doses of ranolazine on number of angina attacks per week. Notes: Placebo indicates treatment only with another anti-anginal drug (atenolol 50 mg, amlodipine 5 mg, diltiazem 180 mg). Data are mean ± standard error. *P < 0.05 in treatment with ranolazine vs. placebo. b.i.d. = twice daily.

Figure 4

Summary of the effects of ranolazine when added to a maximum dose of amlodipine (10 mg) on the number of angina episodes and nitroglycerin uses per week. Notes: Data are mean ± standard error. *P < 0.05 in treatment with ranolazine vs. placebo.

Figure 5

Summary of the effects of ranolazine when added to a maximum dose of amlodipine (10 mg) on the number of angina episodes per week in three subgroups. Note: Data are mean ± standard error. Abbreviation: LAN, long acting nitrate.