Ranolazine is used in the management of chronic stable angina pectoris. Ranolazine may be used in combination with β-adrenergic blocking agents, calcium-channel blocking agents, nitrates, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blocking agents, antiplatelet therapy, and lipid-lowering therapy. The effect of ranolazine on exercise tolerance or the frequency of anginal attacks appears to be smaller in women than in men.
The current indication for ranolazine is based principally on the results of 2 randomized, double-blind, placebo-controlled trials in patients with chronic stable angina pectoris who remained symptomatic despite treatment with another antianginal agent. In the Efficacy of Ranolazine in Chronic Angina (ERICA) trial, patients who remained symptomatic despite treatment with the maximum recommended adult dosage of amlodipine were randomized to receive ranolazine (500 mg twice daily for 1 week, followed by 1 g twice daily for 6 weeks) or placebo, in combination with amlodipine 10 mg daily and sublingual nitrates as needed; 45% of patients also received long-acting nitrates. During the 6-week comparison period (i.e., following titration to ranolazine 1 g twice daily), the mean frequencies of anginal attacks (3.3 versus 4.3 attacks per week) and of nitroglycerin use (2.7 versus 3.6 doses per week) were lower in patients receiving ranolazine than in those receiving placebo. The magnitude of the treatment effect was smaller in women than in men.
In the Combination Assessment of Ranolazine in Stable Angina (CARISA) trial, patients with chronic stable angina pectoris and coronary artery disease who were symptomatic despite treatment with atenolol, amlodipine, or diltiazem were randomized to receive ranolazine 750 mg or 1 g twice daily or placebo for 12 weeks, in combination with atenolol 50 mg, amlodipine 5 mg, or extended-release diltiazem hydrochloride 180 mg daily and with sublingual nitrates as needed. (The manufacturer states that ranolazine should not be administered concomitantly with diltiazem.) Exercise duration, as measured by exercise treadmill testing, was increased in patients receiving ranolazine compared with those receiving placebo, and the increase was associated with minimal changes in blood pressure and heart rate. At the time of trough plasma ranolazine concentrations (i.e., 12 hours after dosing), treadmill exercise time for patients receiving ranolazine exceeded that for patients receiving placebo by an average of 24 seconds. The effects on exercise duration of the 2 ranolazine dosages (750 mg or 1 g twice daily) were similar. Improvements in exercise tolerance were smaller in women than in men.
In clinical trials, rebound increases in angina, as measured by exercise duration, were not reported following abrupt discontinuance of ranolazine.
In the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial, patients presenting within 48 hours of ischemic symptoms were randomized to receive either ranolazine (initiated IV and followed by oral ranolazine extended-release 1000-mg tablets twice daily) or matching placebo for a median of 348 days in addition to standard treatment. Addition of ranolazine to standard treatment for acute coronary syndromes has not been shown to reduce major cardiovascular events However, the cumulative incidence of recurrent ischemia was significantly lower in patients allocated to ranolazine compared with those allocated to placebo. No difference between the two groups in the occurrence of cardiovascular death, myocardial infarction, or severe recurrent ischemia was observed. Findings of this study together with observed favorable overall profile of safety, provided additional evidence to guide the use of ranolazine as antianginal therapy in patients with chronic angina.