Author + information
- Received February 10, 2013
- Revision received February 18, 2013
- Accepted February 19, 2013
- Published online May 21, 2013.
- Mikhail Kosiborod, MD⁎,†,⁎ (, )
- Suzanne V. Arnold, MD, MHA⁎,†,
- John A. Spertus, MD, MPH⁎,†,
- Darren K. McGuire, MD, MHSC‡,
- Yan Li, PhD⁎,
- Patrick Yue, MD§,
- Ori Ben-Yehuda, MD§,
- Amos Katz, MD∥,
- Philip G. Jones, MS⁎,
- Ann Olmsted, PhD§,
- Luiz Belardinelli, MD§ and
- Bernard R. Chaitman, MD¶
- ↵⁎Reprint requests and correspondence:
Dr. Mikhail Kosiborod, Saint Luke's Mid America Heart Institute, 4401 Wornall Road, Kansas City, Missouri 64111
Objectives This study sought to examine the efficacy of ranolazine versus placebo on weekly angina frequency and sublingual nitroglycerin use in subjects with type 2 diabetes mellitus, coronary artery disease (CAD), and chronic stable angina who remain symptomatic despite treatment with up to 2 antianginal agents.
Background Patients with diabetes have more extensive CAD than those without diabetes, and a high burden of angina. Ranolazine is not only effective in treating angina but also may improve glycemic control, thus providing several potential benefits in this high-risk group. We conducted a randomized trial to test the antianginal benefit of ranolazine in patients with diabetes and stable angina.
Methods TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina) was an international, randomized, double-blind trial of ranolazine versus placebo in patients with diabetes, CAD, and stable angina treated with 1 to 2 antianginals. After a single-blind, 4-week placebo run-in, patients were randomized to 8 weeks of double-blind ranolazine (target dose 1000 mg bid) or placebo. Anginal episodes and nitroglycerin use were recorded with daily entry into a novel electronic diary. Primary outcome was the average weekly number of anginal episodes over the last 6 weeks of the study.
Results A total of 949 patients were randomized across 104 centers in 14 countries. Mean age was 64 years, 61% were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c was 7.3%. Electronic diary data capture was 98% in both groups. Weekly angina frequency was significantly lower with ranolazine versus placebo (3.8 [95% confidence interval (CI): 3.6 to 4.1] episodes vs. 4.3 [95% CI: 4.0 to 4.5] episodes, p = 0.008), as was the weekly sublingual nitroglycerin use (1.7 [95% CI: 1.6 to 1.9] doses vs. 2.1 [95% CI: 1.9 to 2.3] doses, p = 0.003). There was no difference in the incidence of serious adverse events between groups.
Conclusions Among patients with diabetes and chronic angina despite treatment with up to 2 agents, ranolazine reduced angina and sublingual nitroglycerin use and was well tolerated. (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina [TERISA]; NCT01425359)
The study was sponsored by Gilead Sciences (Foster City, California). Saint Luke's Mid America Heart Institute received funding for the independent statistical analysis of the TERISA trial from Gilead Sciences. Saint Luke's Mid America Heart Institute received research funding from Gilead Sciences, unrelated to the TERISA trial. Dr. Kosiborod has received research support from Gilead Sciences, unrelated to the TERISA trial; as well as research support from the American Heart Association, Medtronic Minimed, Genentech, Sanofi-Aventis and Glumetrics; and is a consultant for Gilead Sciences, Genentech, F Hoffmann-La Roche, Boehringer-Ingelheim, Medtronic Minimed, and CardioMEMS. Dr. Arnold has received research support from Gilead Sciences, unrelated to the TERISA trial; as well as research support from Genentech, Sanofi-Aventis, and Eli Lilly; and has served on the advisory board for Gilead Sciences. Dr. Spertus has received research support from Gilead Sciences, unrelated to the TERISA trial; as well as research support from NHLBI, ACCF, AHA, PCORI, Amorcyte, Genentech, and Eli Lilly; is a consultant for Gilead Sciences, Genentech, Amgen, United Healthcare (Scientific Advisory Group), and St. Jude Medical; is a board member for Health Outcomes Sciences; and holds patent for SAQ, KCCQ, PAQ, and Prism tool. Dr. McGuire is a consultant for Janssen Pharmaceuticals, Daiichi Sankyo, Pfizer, Boehringer-Ingelheim, Regeneron, Genentech, F Hoffmann-La Roche, Merck, Bristol-Myers Squibb, Tethys Biosciences, AstraZeneca, Orexigen, Eli Lilly, and Takeda. Dr. Yue, Dr. Ben Yehuda, Dr. Belardinelli, and Dr. Olmsted are employees of and own stock and stock options in Gilead Sciences. Dr. Katz has received funding support from Gilead Sciences for the conduct of the TERISA trial. Dr. Chaitman has received research support from Gilead Sciences, unrelated to the TERISA trial; as well as research support from NHLBI; serves as consultant for Gilead Sciences, Merck, Pfizer, Forest Pharmaceuticals, Takeda, Eli Lilly, Sanofi-Aventis, and Roche; is on the speaker's bureau for Gilead Sciences; and has received lecture honoraria from Gilead Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 10, 2013.
- Revision received February 18, 2013.
- Accepted February 19, 2013.
- American College of Cardiology Foundation