Ranolazine is well tolerated; the major adverse effects are constipation, nausea, dizziness, and headache. The incidence of syncope is ,1%. 4.4.3.1.5. Antianginal Agents Not Currently Available in the United States 4.4.3.1.5.1. Nicorandil. Nicorandil is a nicotinamide ester with a dual mechanism of action. It activates adenosine triphosphate sensitive potassium channels and promotes sys- temic venous and coronary vasodilation through a nitrate moiety.893 This dual action increases coronary blood flow, with reductions in afterload, preload, and oxidative injury.893 The agent does not exhibit effects on contractility or conduc- tion.894,895 The antianginal efficacy and safety of nicorandil are similar to those of oral nitrates, beta blockers, and calcium channel blockers.893,896,897 In a prospective, randomized, study of 5126 patients with chronic stable angina, the addition of nicorandil to standard therapy was found to produce a 17% RR reduction in the composite endpoint of IHD death, nonfatal MI, or unplanned hospital admission for cardiac chest pain.898 There was, however, no difference between nicorandil and placebo with regard to death from IHD or nonfatal MI.894 Tolerance can develop with long-term dos- ing.899 Common side effects include flushing; palpitation; weakness; headache; ulceration of the mouth, perianal, ileal, and peristomal areas; nausea; and vomiting. The agent is not currently available in the United States. 4.4.3.1.5.2. Ivabradine. Ivabradine is a specific inhibitor of the If current of pacemaker cells in the sinoatrial node at concentrations that do not inhibit other cardiac currents.900 This action results in heart rate reduction, prolonging diastole and thereby improving myocardial oxygen balance. 