Efficacy of Ranolazine in Chronic Angina - ERICA


The goal of the trial was to evaluate the effect of ranolazine compared with placebo on angina frequency among patients with stable chronic angina already treated with the maximal dose of amlodipine.

Study Design

Study Design:

Patients Enrolled: 565
Mean Follow Up: 6 weeks
Mean Patient Age: Mean age 62 years
Female: 27

Patient Populations:

Age ≥18 years, documented history of CAD, chronic stable angina ≥3 months, and ≥3 episodes of angina per week during a ≥2-week qualification period despite treatment with 10 mg/d amlodipine


New York Heart Association class IV heart failure; a history of myocardial infarction or unstable angina within the previous 2 months; active acute myocarditis; pericarditis; hypertrophic cardiomyopathy; uncontrolled hypertension; history of torsades de pointes; those receiving agents known to prolong the QTc interval; QTc interval measurement >500 ms at study entry; those receiving inhibitors of cytochrome P450-3A4; clinically significant hepatic disease; creatinine clearance <30 ml/min; chronic illness; and use of digitalis, perhexiline, trimetazidine, beta-blockers, or calcium channel blockers other than amlodipine

Primary Endpoints:

Weekly average frequency of self-reported angina episodes during the 6-week treatment phase

Secondary Endpoints:

Weekly average nitroglycerin consumption during the 6-week treatment phase; change from baseline of the 5 dimensions of the SAQ

Drug/Procedures Used:

Patients at the maximal dose of amlodipine (10 mg/d) were randomized to ranolazine (1000 mg; n = 281) or placebo (n = 284) twice a day for 6 weeks.

Concomitant Medications:

All patients were treated with amlodipine (10 mg/d).

Principal Findings:

Baseline characteristics were similar between treatment groups, with an average of 5.59 and 5.68 anginal attacks/week at baseline in the ranolazine and placebo groups, respectively (p = 0.48).

At 6-week follow-up, the primary endpoint of mean anginal attacks/week was lower in the ranolazine group compared with the placebo group (2.88 vs. 3.31, p = 0.028). Average weekly nitroglycerin consumption was also lower in the ranolazine group (2.03 vs. 2.68, p = 0.014). Seattle Angina Questionnaire (SAQ) angina frequency was significantly improved in the ranolazine group versus placebo (18.5 vs. 22.5, p = 0.008), but there was no difference in the other SAQ components. The frequency of adverse events was similar between groups (39.9% for ranolazine and 35.3% for placebo), with constipation the most frequently reported adverse event (8.9% for ranolazine and 1.8% for placebo).


Among patients with stable chronic angina already treated with the maximal dose of amlodipine, the addition of ranolazine was associated with a reduction in the average frequency of weekly anginal episodes at 6 weeks compared with placebo.

Prior studies have demonstrated improvements in exercise tolerance with ranolazine alone or with standard doses of anginal medications, but the present trial extends these findings to patients with persistent angina despite maximal dosing of amlodipine. Results were consistent in the subgroups shown, including those on long-acting nitrates and by degree of angina symptoms at baseline. Additional groups not included in the study but that would be of interest are those on beta-blockers and other calcium channel blockers.


Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol 2006;48:566-75.

Clinical Topics: Stable Ischemic Heart Disease, Chronic Angina

Keywords: Exercise Tolerance, Follow-Up Studies, Angina, Stable, Constipation, Nitrates, Piperazines, Amlodipine, Questionnaires, Calcium Channel Blockers, Nitroglycerin

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