The ERICA Trial Peter H. Stone, MD, FACC, Nikolay A. Gratsiansky, MD, Alexey Blokhin, MD, I-Zu Huang, MD, Lixin Meng, MS, MPH, for the ERICA Investigators Journal of The American College of Cardiology The Efficacy of Ranolazine in Chronic Angina Trial

www. Clinical trial results.org ERICA Trial: Background Ranolazine is a unique antianginal agent that has been effective in stable angina, but it has not been studied in the setting of maximum recommended doses of conventional antianginal agents.Ranolazine is a unique antianginal agent that has been effective in stable angina, but it has not been studied in the setting of maximum recommended doses of conventional antianginal agents. The purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipineThe purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipine. Ranolazine is a unique antianginal agent that has been effective in stable angina, but it has not been studied in the setting of maximum recommended doses of conventional antianginal agents.Ranolazine is a unique antianginal agent that has been effective in stable angina, but it has not been studied in the setting of maximum recommended doses of conventional antianginal agents. The purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipineThe purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipine. JACC Vol. 48 No. 3, 2006

www. Clinical trial results.org ERICA Trial: Study Design JACC Vol. 48 No. 3, 2006  Primary Endpoint: Weekly average frequency of self-reported angina episodes during the 6-week treatment phase  Secondary Endpoint: Weekly average nitroglycerin consumption during the 6- week treatment phase; change from baseline of the 5 dimensions of the Seattle Angina Questionnaire (SAQ)  Primary Endpoint: Weekly average frequency of self-reported angina episodes during the 6-week treatment phase  Secondary Endpoint: Weekly average nitroglycerin consumption during the 6- week treatment phase; change from baseline of the 5 dimensions of the Seattle Angina Questionnaire (SAQ) 10 mg/d Amlodipine and 1,000 mg Ranolazine twice a day for 6 weeks n= mg/d Amlodipine and 1,000 mg Ranolazine twice a day for 6 weeks n=281 10mg/d AmlodipineandPlacebo twice a day for 6 weeks 10mg/d Amlodipine and Placebo twice a day for 6 weeksn=284 n= patients, 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/day amlodipine. Placebo Controlled. Randomized. Blinded Placebo Controlled. Randomized. Blinded 27% Female, Mean age 62 years, Mean follow up 6 weeks 27% Female, Mean age 62 years, Mean follow up 6 weeks 565 patients, 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/day amlodipine. Placebo Controlled. Randomized. Blinded Placebo Controlled. Randomized. Blinded 27% Female, Mean age 62 years, Mean follow up 6 weeks 27% Female, Mean age 62 years, Mean follow up 6 weeks

www. Clinical trial results.org ERICA Trial: Primary Endpoint ERICA Trial: Primary Endpoint JACC Vol. 48 No. 3, 2006 At 6 weeks follow- up, the mean number of anginal attacks/week was lower in the ranolazine group compared with the placebo group (2.88 vs 3.31, p=0.028).At 6 weeks follow- up, the mean number of anginal attacks/week was lower in the ranolazine group compared with the placebo group (2.88 vs 3.31, p=0.028). Primary Endpoint of Mean Anginal Attacks per week p=0.028

www. Clinical trial results.org ERICA Trial: Secondary Endpoint JACC Vol. 48 No. 3, 2006 The average weekly nitroglycerin consumption was lower in the ranolazine group (2.03 vs 2.68, p=0.014).The average weekly nitroglycerin consumption was lower in the ranolazine group (2.03 vs 2.68, p=0.014). Average weekly nitroglycerin consumption p=0.014

www. Clinical trial results.org ERICA Trial: SAQ Angina Frequency JACC Vol. 48 No. 3, 2006 SAQ angina frequency was significantly improved in the ranolazine group vs placebo (18.5 vs 22.5, p=0.008) but there was no difference in the other SAQ components.SAQ angina frequency was significantly improved in the ranolazine group vs placebo (18.5 vs 22.5, p=0.008) but there was no difference in the other SAQ components. Frequency of SAQ Angina p=0.008

www. Clinical trial results.org ERICA Trial: Adverse Events JACC Vol. 48 No. 3, 2006 The frequency of adverse events was similar between groups (39.9% for ranolazine and 35.3% for placebo), with constipation the most frequently reported AE (8.9% for ranolazine and 1.8% for placebo).The frequency of adverse events was similar between groups (39.9% for ranolazine and 35.3% for placebo), with constipation the most frequently reported AE (8.9% for ranolazine and 1.8% for placebo). Frequency of Adverse Events

www. Clinical trial results.org ERICA Trial: Summary 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.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.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.Results were consistent in the subgroups shown, including those on long-acting nitrates and by degree of angina symptoms at baseline. 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.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.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.Results were consistent in the subgroups shown, including those on long-acting nitrates and by degree of angina symptoms at baseline. JACC Vol. 48 No. 3, 2006