In patients with frequent angina symptoms, does the addition of ranolazine to maximum therapy with amlodipine and nitroglycerin improve symptoms?

Ranolazine (Ranexa), added to maximum dosing of amlodipine, decreases angina episodes and nitroglycerin doses slightly more than placebo does; patients taking ranolazine experienced approximately 1 fewer episode, on average, every 2 weeks. These results occurred in patients with frequent symptoms -- at least 4 anginal episodes per week -- and its effect is likely to be less pronounced in patients with less frequent symptoms. (LOE = 1b)

Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L; ERICA Investigators. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol 2006;48:566-575.  [PMID:16875985]

Randomized controlled trial (double-blinded)

Industry

Concealed

Outpatient (any)

Ranolazine is thought to allow more energy to be produced for every molecule of oxygen delivered to the cells of the heart. The mainly eastern European investigators conducting this study enrolled 565 patients with pronounced symptomatic coronary artery disease and at least 3 episodes of angina weekly despite treatment with 10 mg amlodipine (Norvasc) daily. This is a fairly select group, since patients could not be taking any other antianginal drugs, except long-acting or sublingual nitroglycerin. Almost all patients were white; their average age was 62 years. The participants were randomized, using concealed allocation, to receive either placebo or extended-release ranolazine at a dose of 500 mg twice daily for 1 week, then 1000 mg twice daily for 6 weeks. The addition of either placebo or ranolazine to maximum doses of amlodipine resulted in a pronounced drop in the number of weekly angina episodes, from an average baseline rate of 5.6 episodes per week to an average of 3.3 in the placebo group and 2.9 in the treated group. The difference in rates between placebo and ranolazine, a treatment effect of 0.43 episodes per week, was statistically significant (P = .028). Weekly sublingual nitroglycerin use similarly decreased in both groups and was more pronounced in the treatment group (2.03 vs 2.68 doses per week; P = .014).