title: Glucose-Lowering Medications and Angina Burden in Patients with Stable Coronary Disease: results from the Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina (TERISA) Trial.
abstract: BACKGROUND
  Different classes of glucose-lowering medications have been associated with varying risks of myocardial infarction and cardiovascular death, but their effect on angina is unknown. Therefore, we sought to determine the association of different glucose-lowering medication classes with angina frequency and nitroglycerin (NTG) use.
  
  
  METHODS
  We performed a secondary, observational analysis of the TERISA multinational trial, which evaluated the antianginal effect of ranolazine versus placebo in patients with type 2 diabetes mellitus, documented coronary disease, and a 3-month history of stable angina. Patients recorded angina and NTG use in a daily dairy for 3 weeks prior to randomization, to establish their baseline angina burden for the trial. We then examined the association of different glucose-lowering medication classes with baseline angina and NTG use using multivariable linear regression.
  
  
  RESULTS
  Among 952 patients enrolled, 494 were taking metformin, 504 taking a sulfonylurea, 186 taking insulin, 29 taking DPP-4 inhibitors, 22 taking other glucose-lowering medications, and 68 were diet-controlled only. After adjustment for demographic and clinical factors, patients taking versus not taking sulfonylureas had 1.02 more episodes of angina and used 0.93 more doses of NTG per week (P = .002 and .011, respectively). The weekly angina burden or NTG use was not different for those taking versus not taking metformin (P > .7 for both). Patients taking versus not taking insulin had 0.83 more episodes of angina and used 1.40 more NTG doses per week, increases evident only in those taking insulin without concomitant metformin (Pinteraction < .05 for both).
  
  
  CONCLUSIONS
  Different classes of glucose-lowering medications were associated with varying angina burden in patients with type 2 diabetes mellitus and stable coronary disease. Patients taking sulfonylureas or insulin had more angina and used more NTG, while metformin was not associated with angina burden. Given the increasing prevalence of glucose abnormalities in patients with coronary disease, a better understanding of the relationship between glucose-lowering medications and angina is needed.
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: Fengming
authors.initials: F
authors.lastname: Tang
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yue
authors.affiliation: Yale University School of Medicine, New Haven, CT.
authors.forename: Silvio E
authors.initials: SE
authors.lastname: Inzucchi
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.affiliation: Saint 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: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060050:Angina, Stable / Q000150:complications / Q000188:drug therapy; D001786:Blood Glucose / Q000378:metabolism; D002317:Cardiovascular Agents / Q000008:administration & dosage; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D000069458:Ranolazine / Q000008:administration & dosage; D012189:Retrospective Studies; D000094422:Secondary Data Analysis
chemical_list: D001786:Blood Glucose; D002317:Cardiovascular Agents; D007004:Hypoglycemic Agents; D000069458:Ranolazine