2005 AHA Scientific Sessions: ERICA trial

The anti-anginal agent ranolazine, in phase 3 clinical trials, reduced anginal frequency in patients experiencing 3 or more anginal attacks per week despite daily treatment with amlodipine 10 mg/d said Peter Stone, MD, lead investigator of the Evaluation of Ranolazine in Chronic Angina (ERICA) trial.

"Ranolazine has a novel pharmacodynamic profile with anti-ischemic properties that do not depend on changes in determinants of myocardial oxygen demand of heart rate, blood pressure, and contractility; therefore, it provides complementary therapy to existing agents that depend on hemodynamics," said Dr Stone, co-director of the Samuel A. Levine Cardiac Unit at Brigham and Women's Hospital in Boston, Mass. "It improves the manifestations of ischemia, such as myocardial stiffness and increased wall tension."

Ranolazine acts by inhibiting the late inward sodium current and thereby inhibits all of the subsequent consequences of myocardial ischemia, Dr Stone said.

Similarly, ranolazine has been shown to be effective in combination with other anti-anginal agents in routine doses in reducing angina frequency and time to 1 mm of ST depression and in increasing exercise time, Dr Stone said.

In ERICA, 565 patients with a documented diagnosis of coronary artery disease and at least 3 angina attacks weekly who were already taking the maximum labeled dose of amlodipine (10 mg/d) for at least 2 weeks were randomized to ranolazine 500 mg twice daily titrated up to 1,000 mg twice daily, or placebo. Long-acting nitrates were permitted and used by 45% of patients enrolled.

At baseline, patients had nearly 6 angina attacks per week and required almost 5 nitroglycerin tablets per week.

Compared with placebo, ranolazine significantly decreased the mean number of angina episodes per week (P=.028), improved the angina frequency domain of the Seattle Angina Questionnaire (P=.008), and reduced mean weekly nitroglycerin consumption (P=.014) during the 6-week assessment period.

The treatment effect of ranolazine was consistent across the subgroups analyzed: users versus non-users of long-acting nitrates, men versus women, and patients aged <65 versus ≥65 years.

The anti-anginal effects of ranolazine occurred without significant effects on blood pressure and heart rate, Dr Stone said.

Adverse events were more common in the ranolazine versus the placebo group (21% vs 6%), but serious adverse events occurred in only 1% of each group, and only 1% of patients in each group withdrew from the study due to adverse events.