Author + information
- Received April 1, 2006
- Revision received May 18, 2006
- Accepted May 22, 2006
- Published online August 1, 2006.
- Peter H. Stone, MD, FACC⁎,⁎ (, )
- Nikolay A. Gratsiansky, MD†,
- Alexey Blokhin, MD‡,
- I-Zu Huang, MD§,
- Lixin Meng, MS, MPH§,
- ERICA Investigators
- ↵⁎Reprint requests and correspondence:
Dr. Peter H. Stone, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Objectives The purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipine.
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.
Methods Stable patients with coronary disease and ≥3 anginal attacks per week despite maximum recommended dosage of amlodipine (10 mg/day) were randomized to 1,000 mg ranolazine or placebo twice a day for 6 weeks. Primary end point was the frequency of angina episodes per week during the double-blind treatment phase. Efficacy was also assessed by nitroglycerin consumption per week and the Seattle Angina Questionnaire (SAQ). Adjustment for multiple testing of secondary end points used a hierarchic closed testing procedure. Efficacy was assessed in subgroups based on baseline angina frequency, concomitant long-acting nitrate use, gender, and age. Safety was assessed by adverse events and electrocardiogram evaluations.
Results A total of 565 patients were randomized: 281 patients to ranolazine and 284 patients to placebo. Baseline characteristics were similar between treatment groups. At baseline, angina frequency averaged 5.63 ± 0.18 episodes/week, and nitroglycerin consumption averaged 4.72 ± 0.21 tablets/week. Compared with placebo, ranolazine significantly reduced frequency of angina episodes (2.88 ± 0.19 on ranolazine vs. 3.31 ± 0.22 on placebo; p = 0.028) and nitroglycerin consumption (2.03 ± 0.20 on ranolazine vs. 2.68 ± 0.22; p = 0.014), with treatment effect that appeared consistent across subgroups. The median angina weekly episode rate at baseline was 4.5 per week. Subgroup analysis showed statistically significant reductions of angina frequency, nitroglycerin use, and SAQ angina frequency for patients with a baseline frequency >4.5 per week but only of angina frequency for those with baseline frequency ≤4.5 per week. Patients with more frequent angina appeared to have a more pronounced treatment effect. No hemodynamic changes were observed. Ranolazine was well tolerated.
Supported by CV Therapeutics, Palo Alto, California. Dr. Stone has served on an advisory board and is a consultant for CV Therapeutics, has received grant support from Pfizer, Boston Scientific Corporation, and Novartis, and has given lectures for Pfizer. Prof. Gratsiansky and Dr. Blokhin were investigators for the ERICA study, and their institutions received financial support for their participation. Dr. Huang and Ms. Meng are employees of CV Therapeutics.
- Received April 1, 2006.
- Revision received May 18, 2006.
- Accepted May 22, 2006.
- American College of Cardiology Foundation