title: Effectiveness of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina according to baseline hemoglobin A1c.
abstract: BACKGROUND
  Ranolazine reduces the frequency of angina and use of sublingual nitroglycerin (SL NTG) in stable angina patients with type 2 diabetes (T2DM). Because pre-clinical data suggest that myocardial late sodium current (INaL), the target of ranolazine, is increased by hyperglycemia, we investigated whether the efficacy of ranolazine was influenced by glycemic control.
  
  
  METHODS
  TERISA was a multinational, randomized, double-blind trial of ranolazine vs. placebo in patients with T2DM and stable angina. Anginal episodes and SL NTG use were recorded daily in an electronic diary. Health status was evaluated at baseline and 8weeks post-randomization using the Seattle Angina Questionnaire (SAQ). The interaction between baseline HbA1c and treatment effect was tested across endpoints using analysis of covariance models, with HbA1c as a continuous variable with restricted cubic splines.
  
  
  RESULTS
  The study included 913 patients, with mean age 63.6years, 39% women, mean T2DM duration 7.4years, and mean HbA1c of 7.3%. Heterogeneity of efficacy by HbA1c was observed for the primary endpoint of angina frequency (Pinteraction = .027), the key secondary endpoint of SL NTG use (Pinteraction = .030), SAQ angina frequency (Pinteraction = .001), and SAQ treatment satisfaction (Pinteraction = .025) with greater efficacy of ranolazine in those with higher HbA1c values, increasing continuously from HbA1c levels >6.5%.
  
  
  CONCLUSIONS
  Among patients with T2DM and stable angina, the therapeutic benefits of ranolazine were greater in those with higher HbA1c values. These data suggest that ranolazine is particularly beneficial in patients with stable angina who have suboptimally controlled T2DM.
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO; University of Missouri-Kansas City, Kansas City, MO. Electronic address: suz.v.arnold@gmail.com.
authors.forename: Suzanne V
authors.initials: SV
authors.lastname: Arnold
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO; University of Missouri-Kansas City, Kansas City, MO.
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yue
authors.affiliation: Cardiovascular Research Foundation, New York, NY.
authors.forename: Ori
authors.initials: O
authors.lastname: Ben-Yehuda
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Jones
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Ann
authors.initials: A
authors.lastname: Olmsted
authors.affiliation: St. Louis University, St. Louis, MO.
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Chaitman
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO; University of Missouri-Kansas City, Kansas City, MO.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kosiborod
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage*; D060050:Angina, Stable / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D000069458:Ranolazine; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000083:Acetanilides; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D010879:Piperazines; D000069458:Ranolazine