title: Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina).
abstract: OBJECTIVE
  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).
authors.affiliation: Department of Cardiovascular Research, Saint Luke's Mid America Heart Institute, Kansas City, Missouri 64111, USA. mkosiborod@saint-lukes.org
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kosiborod
authors.forename: Suzanne V
authors.initials: SV
authors.lastname: Arnold
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Patrick
authors.initials: P
authors.lastname: Yue
authors.forename: Ori
authors.initials: O
authors.lastname: Ben-Yehuda
authors.forename: Amos
authors.initials: A
authors.lastname: Katz
authors.forename: Philip G
authors.initials: PG
authors.lastname: Jones
authors.forename: Ann
authors.initials: A
authors.lastname: Olmsted
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Chaitman
mesh_terms: D000083:Acetanilides / Q000627:therapeutic use*; D000368:Aged; D060050:Angina, Stable / Q000150:complications / Q000188:drug therapy*; D003324:Coronary Artery Disease / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use*; D000069458:Ranolazine; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D000083:Acetanilides; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D005996:Nitroglycerin; D010879:Piperazines; D000069458:Ranolazine; D026941:Sodium Channel Blockers; D014665:Vasodilator Agents; C517652:hemoglobin A1c protein, human